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Biomedical subjects

O Nilsson

Publications and source records attributed to O Nilsson.

At least 91 records · Page 5Linked to original sources
PubMed1998

Adrenocortical carcinoma: surgery and mitotane for treatment and steroid profiles for follow-up.

Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. It has been difficult to establish a strict treatment program for ACC, and better treatment alternatives and diagnostic tools must be sought. Even though surgery is the treatment of choice, the role of surgery in advanced disease has been questioned. Eighteen consecutive patients were treated at our unit over a 22-year period (1975-1997). All patients underwent surgery and were followed by our protocol, which includes urinary steroid profiles, clinical examinations, analysis of steroid hormones, and radiologic investigations. Twelve patients received mitotane with drug concentration measurements to deliver an effective, nontoxic dose. The median duration of mitotane treatment was 12 months. Few side effects were observed. Four patients with low-stage tumors underwent second-look operations with no pathologic findings. Five patients were subjected to repeat operations, and the mean duration of the disease-free interval before repeat surgery for these patients was 59 months. There was a significant positive correlation between the disease-free interval and the observed survival after repeat surgery. Eleven patients with intentionally curative surgery had their urinary steroid profiles tested several times postoperatively. For five patients preoperative urine samples were also available. Steroid profiles indicated recurrent disease despite normal radiologic findings in two of these five patients. The follow-up ranged from 6 weeks to 24 years. The predicted 5-year survival was 58% according to the Kaplan-Meier method. We conclude that monitoring serum concentrations of mitotane makes long-term treatment possible with few side effects; steroid profile analysis can be used for early detection of tumor recurrence; and repeat surgery for recurrence is of value for patients with long disease-free intervals.

17-Hydroxycorticosteroids↗
PubMed1998

Somatostatin receptor subtypes, octreotide scintigraphy, and clinical response to octreotide treatment in patients with neuroendocrine tumors.

Several types of neuroendocrine tumor express high numbers of somatostatin receptors (sstr). We have compared the expression of sstr subtypes with the outcome of octreotide scintigraphy in patients with carcinoids and medullary thyroid carcinoma (MTC) in comparison with Hürthle cell tumors. The effect of sstr activation (octreotide treatment) on tumor markers was also studied in patients with disseminated carcinoid tumors. Six patients with carcinoid tumors (four midgut and two foregut), and three patients with thyroid tumors (one MTC, one Hürthle cell carcinoma, and one Hürthle cell adenoma) were studied. Octreotide scintigraphy visualized tumor sites in all nine patients. Macroscopic tumor was verified at these sites at subsequent surgical exploration. Using Northern blotting and subtype-specific riboprobes, sstr could be detected in all tumors examined. All five sstr subtypes were detected in most of the carcinoid tumors. All six carcinoids expressed sstr2. This was in contrast to the findings for the thyroid tumors analyzed, which also expressed several sstr subtypes but in some cases lacked expression of sstr2. This was also the case for normal thyroid tissue. Clinically, octreotide treatment of the patients with midgut carcinoid tumors resulted in palliation of hormonal symptoms accompanied by a significant reduction of urinary 5-HIAA levels (28-71%). These results indicate that carcinoid tumors frequently express all five sstr subtypes. The thyroid tumors also expressed multiple sstr but could lack expression of sstr2. Nevertheless, these tumors were visualized by octreotide scintigraphy, indicating that sstr2 expression is not a prerequisite for tumor imaging.

Adenocarcinoma↗
PubMed1998

Anaplastic giant cell carcinoma of the thyroid gland: treatment and survival over a 25-year period.

Anaplastic giant cell carcinoma of the thyroid is a rare but highly malignant tumor. At the Karolinska Hospital in Stockholm, surgery, chemotherapy, and radiotherapy have been used separately or in various combinations in 81 patients admitted with this diagnosis during 1971-1997. In this study, we present the various multimodality treatment regimens and their changes over the years and the subsequent differences in survival and local tumor control. Overall, eight patients (10%) survived more than 2 years. All survivors were treated with combinations of chemotherapy, radiotherapy, and surgery. Among the patients who died, local tumor control was achieved by the therapy given in many cases. The results suggest that our current strategy with a combination of preoperative hyperfractionated accelerated radiotherapy, doxorubicin pre- and postoperatively, and debulking surgery whenever possible results in better local tumor control and an increased chance of survival.

Adult↗
PubMed1998

Comparative studies on the expression of somatostatin receptor subtypes, outcome of octreotide scintigraphy and response to octreotide treatment in patients with carcinoid tumours.

We have compared the expression of somatostatin receptor (sstr) subtypes with the outcome of somatostatin receptor scintigraphy and the effect of somatostatin receptor activation in patients with disseminated carcinoid tumours. Tumour tissues from nine patients with midgut carcinoids (ileal) and three patients with foregut carcinoids (gastric, thymic) were analysed using Northern blotting. Expression of somatostatin receptors was demonstrated in all tumours (12 out of 12), with all five receptor subtypes present in 9 out of 12 tumours. Somatostatin receptor scintigraphy using [111In]DTPA-D-Phe1-octreotide visualized tumours in all patients (12 out of 12). The 111In activity concentrations in tumour tissue (T) and blood (B) were determined in three tumours 1-7 days after injection of the radionuclide. The T/B 111In activity concentration ratios ranged between 32 and 651. Clinically, treatment with the long-acting somatostatin analogue octreotide resulted in marked symptom relief accompanied by a significant reduction in tumour markers, for example urinary-5-HIAA levels (28-71% reduction). Incubation of midgut carcinoid tumours in primary culture with octreotide (10 microM) resulted in a reduction in spontaneously secreted serotonin (45-71% reduction) and 5-HIAA (41-94% reduction). The results demonstrate that carcinoid tumours possess multiple somatostatin receptor subtypes and that somatostatin analogues such as octreotide, which preferentially bind to somatostatin receptor subtype 2 and 5, can be used in the diagnosis and medical treatment of these tumours. In the future, novel somatostatin analogues with subtype specific receptor profiles may prove to be of value for individualizing the treatment of disseminated carcinoid tumour disease.

Aged↗
PubMed1998

Acromegaly and Cushing's syndrome due to ectopic production of GHRH and ACTH by a thymic carcinoid tumour: in vitro responses to GHRH and GHRP-6.

A 50-year-old male presented with diabetes mellitus and Cushing's syndrome associated with a large mediastinal mass. The levels of serum cortisol were high (1500-1800 nmol/l) without diurnal variation. Plasma ACTH levels (200-250 ng/l) and urinary excretion of cortisol were also increased. The levels of these hormones did not change in response to stimulation with corticotrophin releasing hormone (CRH) or suppression with high doses of dexamethasone. The patient had an elevated baseline GH level (7.3 mU/l), and the levels of immunoreactive GH-releasing hormone (GHRH) in eight plasma samples were markedly increased (600-1500 ng/l). Circulating levels of IGF-1, chromogranin A and neuropeptide Y (NPY) were also increased. Computer-assisted tomography and octreotide scintigraphy revealed a large mediastinal tumour and metastases in the left supraclavicular fossa. During treatment with octreotide, the baseline GH level was decreased (to 4.4 mU/l), while the GH pulse height was unchanged. Surgical removal of most of the tumour tissue resulted in a further decrease in the baseline serum GH level to a value (1.6 mU/l) about 20% of that before treatment, while the pulse height and mean GH were affected to a lesser extent. Postoperatively, circulating levels of cortisol and IGF-1 decreased, and the patient exhibited clinical improvement. Histological examination showed a neuroendocrine tumour with characteristics consistent with a foregut carcinoid of thymic origin. Immunoreactive GHRH, ACTH and NPY, but not immunoreactive GH, were detected in 80-90% of the tumour cells and the three peptides appeared to be co-localized. In primary culture, cells from this tumour displayed calcium influx in response to GHRH or GH releasing peptide-6 (GHRP-6), while there were not such responses by cells from another carcinoid not producing GHRH, ACTH or NPY. These results demonstrate a rare case of ectopic production of GHRH, ACTH and NPY, and indicate that the tumour cells were responsive to GHRH and GHRP-6 as well as octreotide.

Acromegaly↗
PubMed1998

Genetic ablation of flowers in transgenic Arabidopsis.

We have created transgenic Arabidopsis plants in which a gene encoding the cell-autonomous diphtheria toxin A chain (DT-A) was expressed under the control of the LEAFY (LFY) promoter. This promoter is active both in emerging leaf primordia and young flowers, with the highest activity in flowers. The majority of LFY::DT-A plants had normal vegetative development but lacked flowers, demonstrating that relatively widespread activity of a promoter does not exclude its possible use for ablating selected tissues, as long as differences in activity levels between different tissues are significant. We also found that flowers were replaced by empty bracts in LFY::DT-A plants, suggesting that flower-derived signals normally suppress bract development in Arabidopsis.

Arabidopsis↗
PubMed1998

Aspirin-induced gastritis, like Helicobacter pylori-induced gastritis disinhibits acid secretion in humans: relation to cytokine expression.

BACKGROUND: Helicobacter pylori infection contributes to hypergastrinemia and hypersecretion of acid by blocking inhibitory reflex pathways to gastrin and parietal cells normally activated by antral distention. Our aim was to investigate whether a similar blockade of inhibitory responses could be provoked by inducing gastritis with aspirin, thus implicating a common inflammatory component, possibly a proinflammatory cytokine(s). METHODS: We studied the effects of antral distention on stimulated acid secretion and gastrin release in H. pylori-negative volunteers, before and after 3 days of aspirin therapy (2 g daily). Immediately before the examinations, the severity of gastric mucosal injury was evaluated macroscopically and histologically, and the production of interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma was determined by immunohistochemistry. RESULTS: Most subjects had severe gastric injury after aspirin therapy, resulting in a substantially increased production of IL-1beta, IL-6, and IL-8 but not of TNF-alpha and IFN-gamma in the antral mucosa. In these subjects the acid-inhibitory response was abolished or markedly reduced. Conversely, aspirin therapy failed to affect the gastrin release in all subjects studied. CONCLUSIONS: The disinhibition of acid secretion in response to antral distention is a joint feature of the gastritis induced by aspirin and H. pylori infection, possibly related to the increased production of IL-1beta, IL-6, and IL-8. The H. pylori-related hypergastrinemia apparently has a different background.

Adult↗
PubMed1998

Flowering-time genes modulate the response to LEAFY activity.

Among the genes that control the transition to flowering in Arabidopsis is a large group whose inactivation causes a delay in flowering. It has been difficult to establish different pathways in which the flowering-time genes might act, because mutants with lesions in these genes have very similar phenotypes. Among the putative targets of the flowering-time genes is another group of genes, which control the identity of individual meristems. Overexpression of one of the meristem-identity genes, LEAFY, can cause the precocious generation of flowers and thus early flowering. We have exploited the opposite phenotypes seen in late-flowering mutants and LEAFY overexpressers to clarify the genetic interactions between flowering-time genes and LEAFY. According to epistatic relationships, we can define one class of flowering-time genes that affects primarily the response to LEAFY activity, and another class of genes that affects primarily the transcriptional induction of LEAFY. These observations allow us to expand previously proposed models for the genetic control of flowering time.

Arabidopsis Proteins↗
PubMed1998

Stability of free and total prostate specific antigen in serum from patients with prostate carcinoma and benign hyperplasia.

PURPOSE: Instability of prostate specific antigen (PSA) in serum might complicate the interpretation of the free-to-total PSA ratio. We studied the in vitro stability of free PSA and total PSA in serum of patients with prostate cancer or benign prostate hyperplasia (BPH), and of elderly men without known prostate disease. Furthermore, we investigated conditions to stabilize the in vitro values in serum. MATERIALS AND METHODS: The effects of storage at 4C on free and total PSA were investigated in serum of 32 men with prostate cancer, 25 with BPH and 29 older than 70 years. All had total PSA less than 25 microg./l. The influence of total PSA levels on in vitro changes in free-to-total PSA was studied in serum of 39 other prostate cancer patients (total PSA 1.7 to 298 microg./l.). Stabilization studies were performed in yet another series of samples from 54 prostate cancer patients (total PSA 1.3 to 238 microg./l.) by adjustment of serum pH to 5.5 before storage. Free and total PSA was measured by a commercial immunofluorometric assay, as well as by in-house immunofluorometric assays. Statistical analyses of the results were performed by analysis of variance with repeated measures. RESULTS: We found no difference between the results obtained by the 2 assay systems. After 7 days at 4C there was a slight decrease in total PSA in sera of prostate cancer patients, BPH patients and men older than 70 years. A decrease in mean free PSA values occurred in all groups (21.3, 15.7 and 14.6%, respectively). The decrease of free PSA with time was significant (p <0.0001) in all groups but there was no significant difference among the groups (p=0.16). The concomitant decrease in free-to-total PSA ratio was significant in all groups (p <0.0001). This change was group dependent (p=0.003), with the largest decrease in the prostate cancer group. Large interindividual differences were observed. Storage at 4C for 7 days of sera of 39 patients with localized and disseminated prostate cancer (total PSA 1.7 to 298 microg./l.) gave a more pronounced decrease in free PSA than in total PSA. Adjustment of serum pH to 5.5 had a stabilizing effect on free PSA and on the free-to-total PSA ratio, giving a significantly smaller change in both values (p <0.0001). CONCLUSIONS: In vitro instability of free PSA in serum and large interindividual differences should be considered when using the ratio of free-to-total PSA in evaluation of patients with suspected prostate cancer. Serum samples should be stored frozen if not analyzed immediately or acidified to pH 5.5. Interpretation of data from determination of free-to-total PSA ratio should be done with caution if the sampling and storage conditions are not known.

Aged↗
PubMed1998

Serum antibodies to H+,K+-ATPase, serum pepsinogen A and Helicobacter pylori in relation to gastric mucosa morphology in patients with low or low-normal concentrations of serum cobalamins.

OBJECTIVES: To compare the diagnostic performance of serum antibodies to H+,K+-ATPase (EC 3.6.1.36), serum pepsinogen A (EC 3.4.23.1) and the Schilling test in diagnosing chronic atrophic body gastritis; to study the interrelationships between H+,K+-ATPase antibodies, serology for Helicobacter pylori, and gastric morphology. DESIGN: Patients with suspected cobalamin deficiency and serum cobalamin < 200 micromol/l were investigated using upper gastrointestinal endoscopy, the Schilling test and serum tests for H+,K+-ATPase antibodies, pepsinogen A, and H. pylori. SETTING: The Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. PATIENTS: Ninety seven consecutively referred patients. MAIN OUTCOME MEASURES: Sensitivity and specificity of assays for serum H+,K+-ATPase antibodies, serum pepsinogen A, and the Schilling test. RESULTS: Assays of serum antibodies to H+,K+-ATPase and of serum pepsinogen A displayed equal diagnostic sensitivity for atrophic gastritis (around 0.90 for the severe forms) and higher than that for the Schilling test (0.65). The diagnostic specificity for pepsinogen A (1.0) was higher than for H+,K+-ATPase antibodies (about 0.80). The prevalence of antral gastritis and positivity for H. pylori antibodies declined with the transition of body gastritis into severe atrophy, while the prevalence of H+,K+-ATPase antibodies increased. CONCLUSION: Pepsinogen A is preferable to serum H+,K+-ATPase antibodies in the diagnosis of gastric body mucosal atrophy. The formation of H+,K+-ATPase antibodies does not seem to be a primary event in the development of gastric body muscosal atrophy.

Adult↗
PubMed1998

Gibberellins promote flowering of arabidopsis by activating the LEAFY promoter

The gibberellin class of plant hormones has been implicated in the control of flowering in several species. In Arabidopsis, severe reduction of endogenous gibberellins delays flowering in long days and prevents flowering in short days. We have investigated how the differential effects of gibberellins on flowering correlate with expression of LEAFY, a floral meristem identity gene. We have found that the failure of gibberellin-deficient ga1-3 mutants to flower in short days was paralleled by the absence of LEAFY promoter induction. A causal connection between these two events was confirmed by the ability of a constitutively expressed LEAFY transgene to restore flowering to ga1-3 mutants in short days. In contrast to short days, impairment of gibberellin biosynthesis caused merely a reduction of LEAFY expression when plants were grown in long days or with sucrose in the dark. As a first step toward identifying other small molecules that might regulate flowering, we have developed a rapid in vitro assay for LEAFY promoter activity.

Journal Article↗
PubMed1998

Gastric carcinoid with histamine production, histamine transporter and expression of somatostatin receptors.

A case of sporadic, histamine-producing gastric carcinoid with liver metastases is reported. The patient was treated with somatostatin analogue (octreotide) combined with cortisone and blockade of histamine receptors prior to surgery, which included subtotal gastrectomy, excision of lymph node metastases and superficial liver metastases. Residual liver metastases were injected with ethanol. These interventions markedly reduced the urinary excretion of the main histamine metabolite (MelmAA). Eighteen months later combined immuno- and chemotherapy was initiated due to tumour progression and recurrent hormonal symptoms with good clinical results over 12 months. Scintigraphy, using 111In-DTPA-D-Phe1-octreotide, visualized somatostatin receptors (sstr) in primary tumour, lymph node metastases and liver metastases. The tissue/blood 111In concentration ratios of tumour biopsies were very high. Northern analyses confirmed expression of all subtypes of sstr1-5. Immunocytochemically, tumour cells were strongly positive for chromogranin A, histamine and vesicular monoamine transporter (VMAT) 2 (histamine transporter), but negative for VMAT 1, suggesting an origin from gastric enterochromaffin-like cells. In primary tumour cell cultures, histamine, 5-HTP and 5-HIAA, but not 5-HT, could be detected in conditioned culture medium, indicating a defective decarboxylation of the tryptamine precursor. This rare case of histamine-producing gastric carcinoid demonstrates that excellent symptom relief can be achieved despite disseminated disease, if active, multimodal treatment strategy is instituted. The presence of high numbers of sstr in tumour tissue also raises the possibility of receptor-guided radiotherapy.

Aged↗
PubMed1998

Summary report on the ISOBM TD-6 workshop: analysis of 20 monoclonal antibodies against Sialyl Lewisa and related antigens. Montreux, Switzerland, September 19-24, 1997.

The ISOBM TD-6 Workshop is the first international workshop on monoclonal antibodies against the Sialyl Lewisa (SLea) antigen. Eight research groups participated in a blind study to characterize the epitope binding, relative affinity and performance in immunoradiometric assays, of a panel of 20 monoclonal antibodies. The antibodies were tested against a diverse panel of neoglycoconjugates, purified antigens and human serum pools from gastrointestinal malignancies. Epitope specificities were determined for the majority of antibodies in the panel. Cross-reactivity with related saccharide structures was noted in several antibodies. Overall, the results of the TD-6 Workshop show further development of SLea immunoassays may yield yet more specific assays for the detection and management of gastrointestinal and other malignancies.

Antibodies, Monoclonal↗
PubMed1998

Summary report on the ISOBM TD-4 Workshop: analysis of 56 monoclonal antibodies against the MUC1 mucin. San Diego, Calif., November 17-23, 1996.

Sixteen research groups participated in the ISOBM TD-4 Workshop in which the reactivity and specificity of 56 monoclonal antibodies against the MUC1 mucin was investigated using a diverse panel of target antigens and MUC1 mucin-related synthetic peptides and glycopeptides. The majority of antibodies (34/56) defined epitopes located within the 20-amino acid tandem repeat sequence of the MUC1 mucin protein core. Of the remaining 22 antibodies, there was evidence for the involvement of carbohydrate residues in the epitopes for 16 antibodies. There was no obvious relationship between the type of immunogen and the specificity of each antibody. Synthetic peptides and glycopeptides were analyzed for their reactivity with each antibody either by assay of direct binding (e.g. by ELISA or BiaCore) or by determining the capacity of synthetic ligands to inhibit antibody binding interactions. There was good concordance between the research groups in identifying antibodies reactive with peptide epitopes within the MUC1 protein core. Epitope mapping tests were performed using the Pepscan analysis for antibody reactivity against overlapping synthetic peptides, and results were largely consistent between research groups. The dominant feature of epitopes within the MUC1 protein core was the presence, in full or part, of the hydrophilic sequence of PDTRAPAP. Carbohydrate epitopes were less easily characterized and the most useful reagents in this respect were defined oligosaccharides, rather than purified mucin preparations enriched in particular carbohydrate moieties. It was evident that carbohydrate residues were involved in many epitopes, by regulating epitope accessibility or masking determinants, or by stabilizing preferred conformations of peptide epitopes within the MUC1 protein core. Overall, the studies, highlight concordance between groups rather than exposing inconsistencies which gives added confidence to the results of analyses of the specificity of antimucin monoclonal antibodies.

Amino Acid Sequence↗
PubMed1998

Epitope characterization of MUC1 antibodies.

The specificities of the 56 MAbs submitted to the ISOBM TD-4 Workshop were characterized by ELISA assays against MUC1-positive (ZR75-1) and MUC1-negative cell lines (LS174T), binding to a 20-mer peptide corresponding to the tandem repeat region of MUC1 apoprotein, and Pepscan analysis of overlapping 9-mer peptides corresponding to the tandem repeat region of MUC1. The recognition of soluble MUC1 antigen from ZR75-1 cell line was also tested in two-site EIA using the ISOBM TD-4 MAb as catching MAb. The studies indicated that 35 of the submitted antibodies recognized epitopes expressed in the MUC1 tandem repeat region, and that 30 of these recognized epitopes within the immunodominant region (PDTRPAP) of the tandem repeat. Recognition of soluble MUC1 from ZR75-1 cell line indicated that additional 10 MAb recognized epitopes 'outside' the tandem repeat region of MUC1 from ZR75-1 cell line, or that the antibodies recognized epitopes depending on the glycosylation of the MUC1 tandem repeat. Six MAbs reacted only with the MUC1-negative cell line LS174T, and thus most likely did not recognize epitopes specific for MUC1.

Amino Acid Sequence↗
PubMed1997

Colon adenoma and cancer cells aberrantly express the leukocyte-associated sialoglycoprotein CD43.

CD43 (leukosialin) has hitherto been considered as an exclusive leukocyte marker, but now we report the expression of CD43 in the epithelial cells of all studied colorectal adenomas (21/21) and in about 50% (18/34) of adenocarcinomas as analyzed both at the mRNA and protein levels. Direct evidence showing the causal role of CD43 in colon tumorigenesis is lacking, but its involvement in leukocyte activation and impairment of apoptotic response suggests a role for CD43 in colon cancer development.

Adenocarcinoma↗
PubMed1997

E-cadherin expression in human epithelial ovarian cancer and normal ovary.

The ovarian surface epithelium (OSE) is the origin of the majority of human ovarian cancers. These adenocarcinomas are characterized by initial local growth followed by spreading into the peritoneal cavity at later stages of tumor progression. The cell-adhesion molecule E-cadherin (E-cad) plays an important role in maintaining tissue integrity. Disappearance or impaired function of E-cad have often been associated with tumor formation and invasion in vivo and in vitro. The cell-specific expression of E-cad was investigated in normal human ovaries (n = 12), in benign (n = 5) and borderline (n = 4) ovarian epithelial tumors and in adenocarcinomas of different stages and histological grades (n = 18), by immunohistochemistry and immunoblotting. An ovarian cancer cell line (NIH-OVCAR3) was used as a reference. The epithelial origin of the cells was confirmed with cytokeratin (AE1/AE3) staining. In normal ovaries, the expression of E-cad was limited to inclusion cysts or deep clefts lined with OSE, whereas no staining of the OSE could be demonstrated at the surface of the ovary. In contrast, benign and borderline tumors uniformly expressed E-cad. This was observed in malignant tumors of all stages despite their degree of differentiation. E-cad was also present in metastasis from such tumors. The cell-specific expression of E-cad in inclusion cysts of normal ovaries and in epithelial layers of borderline tumors indicates a role for E-cad in the early events of the progression to a malignant phenotype. E-cad was not downregulated in later stages of ovarian cancer progression.

Adenocarcinoma, Mucinous↗