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Biomedical subjects

O Nilsson

Publications and source records attributed to O Nilsson.

409 records · Page 23Linked to original sources

Characterization of monoclonal antibodies directed against squamous cell carcinoma antigens: report of the TD-10 Workshop.

Thirteen monoclonal antibodies directed against squamous cell carcinoma antigens (SCCA1 and SCCA2) were obtained from five international collaborating laboratories participating in the ISOBM TD-10 Workshop. Native and recombinant forms of SCCA were used in a wide variety of approaches to determine the reactivity and specificity of these antibodies. Based on reactivity, the antibodies could be divided into three groups: the SCCA1-reactive group containing those that reacted only with recombinant SCCA1 (rSCCA1) and native SCCA1 (nSCCA1) antigens, the SCCA2-reactive group containing those that reacted only with recombinant SCCA2 (rSCCA2), and the pan-reactive group containing those antibodies that reacted with rSCCA1, nSCCA1, and rSCCA2. Binding to radioiodinated rSCCA1 showed that all reactive antibodies were of a high affinity (K(d) <2 x 10(-9) mol/l). Binding to labelled rSCCA2 demonstrated that five antibodies were of a high affinity (K(d) <2 x 10(-9) mol/l). Antibody reactivity on Western blots was tested with nonreduced and reduced native and recombinant SCCA1 and SCCA2. In general, these findings showed that reduction had little effect on binding to SCCA1, but often a strong effect on the binding to SCCA2. Binding of antibodies to rSCCA1 and rSCCA2 in complexes with cathepsin L and G, respectively, was used to assist in the localization of epitope regions in enzyme-complexed SCCA. Cross-inhibition experiments showed that SCCA1-reactive antibodies represent two different epitope groups, and this is supported by their ability to make SCCA1-specific assays by combining antibodies from the two epitope groups. The SCCA2-reactive group represents two related antibodies and one unique as seen in cross-inhibition, but they do not form successful assay combinations. Classification of the pan-reactive antibodies is more difficult, as some epitope groups differ when results from rSCCA1 are compared with rSCCA2 as the target. However, two antibodies are outstanding, SCC107 and SCC113, as they are high-affinity antibodies which react equally well with free and protease complexes of SCCA1 and SCCA2. The precise location of epitopes was further studied using sequential overlapping peptides and homology modelling. The findings from this workshop strongly indicate that the recombinant antigens (rSCCA1 and rSCCA2) are very similar in epitope structure to the native counterparts in saliva, and squamous epithelium from normal and cancer tissues. Therefore, it is reasonable to conclude that the specificities found are reliable and have application for antibody measurement of all forms of squamous cell carcinoma in serum except SCCA2 in complex with its protease.

Antibodies, Monoclonal↗

Histamine metabolism of gastric carcinoids in Mastomys natalensis.

Pharmacological inhibition of gastric acid secretion and subsequent hypergastrinemia in Mastomys natalensis is an experimental model well suited for the study of gastric carcinoid formation. The genetic susceptibility of Mastomys to develop such tumors is a feature reminiscent of the situation in patients with the MEN-1 Zollinger Ellison syndrome, in whom tumor-induced hypergastrinemia, promotes the development of gastric carcinoids. Chronic hypergastrinemia, induced by the irreversible H2-receptor antagonist loxtidine will cause carcinoid formation in Mastomys already after four to six months. As in humans, gastric carcinoids in Mastomys are mainly composed of enterochromaffinlike (ECL) cells and have low malignant potential. Administration of exogenous gastrin to normal young animals increases the expression of histidine decarboxylase (HDC) mRNA in the oxyntic mucosa within 30 minutes. Endogenous hypergastrinemia, induced by short-time loxtidine treatment (three to 29 days) enhances the expression of HDC mRNA, histamine contents and ECL cell numbers in the oxyntic mucosa. Long-term loxtidine treatment (seven to 21 months) results in sustained hypergastrinemia and tumor formation. Tumor-bearing animals exhibited an increase in HDC mRNA and histamine content in the oxyntic mucosa as well as increased urinary excretion of the main histamine metabolite, tele-methylimidazole acetic acid (MeImAA). Subsequent to cessation of loxtidine treatment for two weeks, all parameters of histamine metabolism were normalized in tumor-bearing animals. These results indicate that gastric carcinoids developing during hypergastrinemia are well-differentiated neoplasms whose histamine synthesis and metabolism is regulated by plasma gastrin.

Animals↗

Praomys (Mastomys) natalensis: a model for gastric carcinoid formation.

The gastric carcinoid tumors of Praomys (Mastomys) natalensis have been reviewed with respect to histogenesis, development, biochemistry, and morphological properties. Multicentric gastric carcinoids frequently develop in the oxyntic mucosa of aging Mastomys. The development of these tumors can be significantly enhanced by drug-induced hypergastrinemia, e.g., histamine2-receptor blockade. Spontaneous and drug-induced gastric carcinoids are endocrine in nature, as evidenced by their argyrophilic staining properties and chromogranin A content. They are also rich in histidine decarboxylase activity and produce large amounts of histamine, although other hormones, such as peptide YY and enteroglucagon, have also been demonstrated in these tumors. Ultrastructurally, gastric carcinoids are composed of tumor cells with typical secretory granules resembling those of enterochromaffin-like (ECL) cells. A close examination of the gastric carcinoids in Mastomys reveals striking similarities with gastric carcinoids developing in humans suffering from chronic atrophic gastritis type A or from the Zollinger-Ellison syndrome in combination with multiple endocrine neoplasia type 1 (MEN-1). Both these conditions are associated with hypergastrinemia and a higher risk for developing multi-centric gastric carcinoids of ECL-cell origin. The Mastomys tumor model therefore appears to be a significant experimental model in which induction and formation of gastric carcinoid tumors can be studied.

Animals↗

Plasma and tissue alterations of peptide YY and enteroglucagon in rats after colectomy.

Peptide YY (PYY) and enteroglucagon are produced by endocrine cells of the colonic mucosa. PYY inhibits upper gastrointestinal motility, and enteroglucagon is trophic for small bowel mucosa. Adaptive increase in the production and release of these peptides may improve functional results after colorectal resections. We hypothesized that if segments of the colon were resected, then production and release of PYY and enteroglucagon would increase in the remaining segments of bowel. Animals which underwent colonic transections and partial resections had transient elevations of PYY up to 250 +/- 80 pmol/L, which dropped to control group levels in the second week following surgery. Rats with an abdominal colectomy had significantly greater PYY levels than all other groups from the third (208 +/- 30 pmol/L) to the thirty-eighth (100 +/- 16 pmol/L) week of the study. Circulating levels of enteroglucagon were elevated to 156 +/- 35 pmol/L in rats with a right hemicolectomy during the first week following surgery. Enteroglucagon levels did not significantly vary in the other groups studied. Both tissue PYY (413 +/- 33 pmol/gram) and tissue enteroglucagon (171 +/- 17 pmol/gram) were significantly elevated in the rectums of the rats with an abdominal colectomy, as compared to all other groups. The elevated tissue levels may thus account for the ability to maintain elevated plasma PYY. Double immunogold labeling of endocrine cells in the colorectal tissue for PYY and enteroglucagon revealed both peptides within the same endocrine cells and secretory granules. These studies support the hypothesis that circulating levels of PYY are elevated after major colonic resections and suggest that L-type endocrine cells may participate in adaptive responses which improve intestinal function following colonic surgery.

Animals↗

Gd-DTPA-enhanced MR of suspected spinal multiple sclerosis.

A prospective study was undertaken to evaluate the potential of Gd-DTPA-enhanced MR to differentiate active from inactive demyelinating lesions of the cervical spinal cord. Five patients with elongated high-signal-intensity lesions in the cervical cord on long TR/TE spin-echo MR images and a clinical suspicion of demyelinating disease had MR before and after IV Gd-DTPA. Delayed contrast enhancement (after 45-60 min) of the lesions was seen on short TR/TE images in two patients with clinically active disease, but no enhancement could be detected in three patients with stable disease. The patients with active disease underwent repeated MR examinations until the enhancement disappeared. The decrease in Gd-DTPA enhancement paralleled a decrease in clinical signs and symptoms of cervical myelopathy. MR is useful in evaluating patients suspected of having demyelinating disease. The MR finding of asymptomatic lesions in the brain lends support to the diagnosis of multiple sclerosis. Other possible causes of myelopathy, such as spinal cord compression and intramedullary tumor, can be excluded with the use of MR.

Acute Disease↗

The effects of albendazole treatment on spring-rise in faecal nematode egg output and reproductive performance in the ewe.

The effects of albendazole treatment in late autumn and winter on the spring-rise in faecal nematode egg output and reproductive performance in the ewe were investigated. The control measure effectively prevented the egg output in spring and lambs born to treated ewes had increased birthweights in comparison with those born to untreated ewes.

Albendazole↗

The effect of pre-farrowing treatment of the sow with ivermectin on the early establishment of Ascaris suum and Oesophagostomum spp in the progeny.

Residual infective Ascaris suum eggs in farrowing pens provide the initial source of infection for piglets under Swedish management conditions. In such circumstances there is little evidence to support pre-farrowing treatment of the sow specifically against A. suum. The present study shows, however, that ivermectin-treatment of the sow prevents the early establishment of A. suum and Oesophagostomum spp in her litter.

Animals↗

The effect of continuous in-feed medication with thiophanate on Ascaris suum and Oesophagostomum spp. egg output in young pigs.

The full potential of anthelmintics now available for single dose treatment is not achieved because the devising system for worm control in piglets/weaners is not efficiently applicable in practice. Therefore an in-feed medication programme for growing young pigs, allowing only one feed lot to be handled by the farmer, was tested in two studies. Study A Feed containing 0.0225% thiophanate was continuously fed almost ad lib. to piglets from birth right up to about 25 kg body weight when ready for fattening. This control measure effectively prevented A. suum and Oesophagostomum from becoming established during the whole pre-fattening period, thus allowing "worm-free" weaners to be produced. -33% of animals receiving unmedicated feed harboured mature Oesophagostomum already at an age of 63 days when first examined. Three out of 97 unmedicated pigs were then A. suum egg-count positive. At the same time all medicated pigs, except one with a low Oesophagostomum egg output, were egg-count negative. All medicated were still egg-count negative at 23-29 days after the withdrawal of the feed. About 30% of unmedicated pigs were then shedding eggs of A. suum and Oesophagostomum respectively. At 45-49 days after the withdrawal of the medicated feed 8% of previously medicated pigs and 43% of unmedicated pigs were A. suum egg-count positive. The corresponding figures for Oesophagostomum egg-count positive pigs were 6% and 40% respectively. The acquisition of worm infections by previously medicated pigs most probably was made in the fattening unit after the withdrawal of the thiophanate medicated feed. Study B In this study it was further substantiated that in-feed medication of pigs with thiophanate prevents A. suum from becoming established. All treated pigs were A. suum egg-count negative at Day 43 and 46 after the withdrawal of the medicated feed whereas about 62% of untreated control pigs were shedding A. suum eggs at the same time. This finding justify the proposal that the in-feed medication performed prevented larval migration. Furthermore it was shown that the in-feed medication must proceed right up to the transfer of piglets to the fattening unit in order to achieve its full potential. Farrowing pens may be heavily contaminated with infective Oesophagostomum larvae at the end of the pre-fattening period resulting in sudden and heavy nodular worm infections after the withdrawal of the medicated feed.

Animal Feed↗

Epidemiology of porcine neonatal steatorrhoea in Sweden. 1. Prevalence and clinical significance of coccidal and rotaviral infections.

A study of neonatal steatorrhoea in unweaned piglets was carried out in randomly visited herds. Isospora suis and rotavirus were shown to be incriminated in this type of enteric disease and these agents may be considered important enteropathogens for 1-3-week-old piglets in Sweden. More extensive studies of I. suis were undertaken in one large herd. It was found that steatorrhoea may appear in 4-day-old piglets but oocysts were not detected until some days latter. Piglets that were shedding I. suis were not necessarily steatorrhoeic but oocysts were more frequently found in steatorrhoeic faeces than in faeces of normal consistency. The earliest oocyst output was detected at 5 days of age, the average litterage at first appearance being 12.8 +/- 4.0 days. The occurrence of I. suis oocysts in piglets did not correlate with the oocyst output in sows, which almost exclusively included genus Eimeria. Repeated parasitological and virological examination of steatorrhoeic faecal samples from 5-10 litters per herd at an age of 1-3 weeks would be helpful for making a herd diagnosis.

Animals↗

Amitraz--(TAKTIC) for the control of pig mange.

The efficiency of amitraz (TAKTIC) on pig mange was evaluated. Controlled trials as well as a field trial document the high acaricidal activity of the product. Spraying or washing with amitraz in a 0.1 per cent water emulsion twice with 1--2 weeks' interval effectively cure scabietic piglets and strongly reduce scabietic lesions and scratchings in sows with chronical mange. duct. Spraying with amitraz in a 0.1 per cent water emulsion twice with 1--2 weeks interval effectively cure scabietic piglets and strongly reduce scabietic lesions and scratchings in sows with chronical mange.

Administration, Topical↗

Somatostatin receptors on neuroendocrine tumors--a way to intraoperative diagnosis and localization.

Intraoperative radionuclide detection using 111In-DTPA-D-Phe1-octreotide was evaluated in five patients with midgut carcinoids and in three patients with recurrent medullary thyroid carcinoma. Three different time intervals (24, 48 and 120 hr) from injection of the radiopharmaceutical to surgery were used. At surgery, suspect tumors were measured by probe in situ and ex vivo after excision. All tissue specimens and blood samples withdrawn during surgery were measured for 111In activity, and tissue/blood activity concentration ratios were calculated. In situ measurements were valuable especially in neck surgery, where the probe was helpful not only in localization of tumors but also in the control of tumor clearance. Ex vivo measurements were helpful in diagnosing tumor tissue. All five patients with midgut carcinoids were somatostatin receptor-positive, while only three out of seven patients with medullary thyroid carcinoma were receptor-positive. The tissue/blood activity concentration ratios and probe measurement ratios were in general higher in patients with midgut carcinoid than in patients with medullary thyroid carcinoma. Of particular interest were the high tissue/blood concentration ratios in all receptor-positive patients at all time intervals studied. This fact suggests a potential role for radiolabelled octreotide in radiotherapy of these tumor types.

Carcinoid Tumor↗

The relevance of somatostatin receptors in thyroid neoplasia.

111In-octreotide scintigraphy in patients with persistent medullary thyroid carcinoma (MTC) visualized tumors in about half of the surgically explored sites. Tumor visualization correlated with rapid tumor growth and large tumor volume as judged from calcitonin levels. The 111In concentration ratio between tumor (T) and blood (B) in surgically excised lymph node metastases of MTC showed a large variation, with low values for microscopic and high values for macroscopic metastases in individual patients. Three cases of MTC, Hürthle cell adenoma and papillary thyroid cancer are reported with preoperative scintigraphy, T/B ratios and Northern analyses of the surgical biopsies. Visualization of tumors was possible in the absence of sstr2 (the high affinity receptor for octreotide) with the exception of microscopic tumor growth. T/B values in the patient with Hürthle cell adenoma were similar to those found in the contralateral thyroid lobe with goitre. The relatively high uptake of 111In in benign thyroid conditions probably limits the use of octreotide scintigraphy in the diagnosis of primary tumors. The technique has certain advantages over radioiodine scintigraphy after the surgical treatment of thyroid tumors: no need for withdrawal of thyroxin substitution; a possibility to diagnose metastases of tumors that do not concentrate radioiodine (MTC, Hürthle cell cancer); and complementary information about metastatic sites of non-medullary thyroid cancer (papillary and follicular tumors).

Adenoma, Oxyphilic↗