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Biomedical subjects

S Nilsson

Publications and source records attributed to S Nilsson.

At least 577 records · Page 32Linked to original sources
PubMedDate not supplied

Clinical profile of a new monoclonal antibody-based immunoassay for tissue polypeptide antigen.

Our preliminary evaluation of a new monoclonal antibody-based assay for tissue polypeptide antigen (TPA) has shown it to be clinically equivalent to the polyclonal antibody-based assay for TPA. The new assay (TPA-M) employs three monoclonal antibodies to epitopes on cytokeratins 8, 18 and 19. This multicenter, multinational study included 266 patients with newly diagnosed carcinomas of the lung, breast, large bowel and urinary bladder. TPA values from the two assays were compared with three other cytokeratin markers (TPS, CYFRA 21-1 and TPACyk) and with the established reference markers for these malignancies (CEA and NSE for lung, CA 15-3 for breast, CEA and CA 19-9 for colorectal tumors). Analysis of receiver operating characteristic (ROC) curves in lung, colorectal and bladder cancer showed similar sensitivities for the two assays, ranging from 50% to 80% with a specificity of 95%. In breast cancer all the markers studied showed poor sensitivity. However, TPA determination by either method could discriminate advanced stage (stages III and IV) from early stage disease (stages 0 to II). TPA showed similar discriminating ability in bladder cancer. On the basis of the results obtained in our patient series, it seems that of the cytokeratin markers studied, TPA and TPA-M are the most sensitive and offer a wide range of clinical applications.

Antibodies, Monoclonal↗
PubMedDate not supplied

Tinnitus information: a study by questionnaire.

The aim of the present study was to improve the information for patients with tinnitus. The investigation consists of three parts: a pilot study where 24 slightly informed tinnitus patients as well as 17 well-informed tinnitus patients and 9 audiological professionals suggested contents for a tinnitus information pamphlet. The second part consisted of scoring of the 74 most common suggestions by 36 of the original 50 people. The answers were graded according to importance. Three available tinnitus information folders from Sweden, Germany and the USA were also studied and taken into account in preparing recommendations on content and size for a tinnitus information pamphlet. This should probably not exceed 2500 words, and 35 items of information.

Adult↗
PubMedDate not supplied

Serum concentrations of VEGF and b-FGF in renal cell, prostate and urinary bladder carcinomas.

Sixty nine patients with urogenital cancers (renal, bladder and prostate cancer) were studied to determine whether the serum concentrations of Vascular Endothelial Growth Factor (VEGF) and basic Fibroblast Growth Factor (b-FGF) reflected the status of the patients and/or the prognosis of the disease. Of the patients included in this study, renal cell carcinoma patients expressed the highest levels of VEGF indicating that these tumours are more VEGF dependent. The values of b-FGF could be considered normal in all three malignancies. No correlation was observed between the expression of VEGF and b-FGF, nor between VEGF and b-FGF and patients survival.

Adult↗
PubMedDate not supplied

The prevalence of gallstones in chronic liver disease is related to degree of liver dysfunction.

BACKGROUND/AIMS: Earlier studies have indicated an elevated risk for gallstone disease in patients with cirrhosis. This study aimed to evaluate the prevalence of gallstones in patients with chronic liver disease (CLD) with respect to sex, etiology, and severity of liver disease. METHODOLOGY: Four hundred and thirteen adults (176 women), mean age 51.2+/-14 years, with CLD, who had undergone liver biopsy during 1978-1993, and from whom sera were available, were investigated retrospectively. The results were compared with a population-based ultrasonography study of 556 healthy men and women, in their 40s and 60s. RESULTS: The prevalence of gallstones in patients with CLD did not differ from that in the control population. An increased frequency was observed in patients with CLD initially classified as cryptogenic, of whom the majority (60%) later were reclassified as chronic hepatitis C. The frequency of gallstones was also high in PiZ-heterozygotes for alpha1-antitrypsin deficiency (5/21, 24%) compared to non-PiZ-carriers (17/389, 4.8%), (p<0.001). In 67 patients with histologic evidence of cirrhosis, 30% (20/67) had gallstones (vs. 15% in the general population, p<0.01). The prevalence of gallstones increased significantly from Child's class A (16%) to C (56.2%). The difference was significant in males (18.2% vs. 62.5%, p=0.033), but not in females. Fifty percent of the patients with gallstones were symptomatic. CONCLUSIONS: Progressive liver dysfunction is a risk factor for gallstones particularly in males. HCV infection and PiZ carriership may further increase biliary lithogenesis.

Adult↗
PubMedDate not supplied

Human milk fat globule antigen 1 (HMFG1) expression in prostatic carcinoma and immunotargeting with a radiolabelled monoclonal anti-HMFG1 antibody.

BACKGROUND: Prostatic cancer is the leading cause of death in Swedish men. Approximately 50% have disseminated disease at diagnosis. Radiolabelled antibodies could possibly be a treatment modality for disseminated prostatic cancer, so that in this study the expression of the human milk fat globulin 1 (HMFG1) antigen in prostate cancer was examined. MATERIALS AND METHODS: An immunohistochemistry technique with a murine monoclonal antibody was used, as well as the human prostate cancer cell line DU-145, which expresses this cell surface antigen. TUR specimens from patients with prostate cancer were also examined. RESULTS: Eighteen out of 22 (82%) patients exhibited an HMFG1-positive tumour. An inhomogenity in the immunostaining could occasionally be seen, with smaller apparently negative areas. The immunolocalisation properties of the antibody were investigated using a radiolabelled antibody injection into nude mice bearing heterotransplants of the DU-145 cell line. The highest accumulation of the antibody was seen in the tumour tissue and the liver. CONCLUSION: The results obtained form a basis for further investigations with the goal of using the antibodies for staging and therapy for prostate cancer.

Animals↗
PubMedDate not supplied

Postoperative radiotherapy after prostatectomy can be associated with severe side effects.

This retrospective study was initiated to evaluate the efficacy and side effects of post-prostatectomy external beam radiation therapy (XRT) with a short time interval between surgery and irradiation in patients with prostate adenocarcinoma. Sixteen patients were investigated. The overall results in this study were 3 deaths due to recurring disease and two relapses after an average follow-up of 60 months. Severe side effects were observed. Two patients required surgical intervention due to severe post-radiotherapy side effects. The reason for this could be the high dose delivered to peripheral organs and/or a too short time interval between surgery and postoperative XRT. The results of this study confirmed that postoperative XRT can improve local control frequency in prostate carcinomas. It is recommended that the time interval between surgery and postoperative radiotherapy should to be 3-6 month.

Adenocarcinoma↗
PubMedDate not supplied

Diagnostic methods in planning palliation of spinal metastases.

In a prospective study of 30 patients with newly diagnosed spinal metastases the benefit of different imaging techniques in planning palliation was studied. Magnetic resonance imaging (MRI) was compared to scintigraphy, conventional radiography and computerized tomography (CT), prior to radiotherapy or surgery. In the first comparison, a total of 159 pathologic lesions could be evaluated. MRI was superior in the detection of suspect metastases compared to conventional radiography and scintigraphy (P less than 0.0001 and p less than 0.01, respectively). MRI also gave useful information about adjacent soft tissue components, vessels, nerves and spinal cord compression, i.e. useful information when planning stabilizing surgery. Both MRI and CT were sensitive and specific methods but when comparing 120 pathologic lesions the detection rate of MRI was significantly higher than that of CT (p less than 0.01). In conclusion, scintigraphy and conventional radiography are adequate enough if palliative radiotherapy is planned. When considering surgery MRI is advocated preoperatively for defining operability.

Female↗
PubMedDate not supplied

Expression and partial characterization of estramustine-binding protein (EMBP) in human breast cancer and malignant melanoma.

The expression of the estramustine/estromustine-binding protein (EMBP) in human mammary cancer and malignant melanoma was examined by immunochemical methods and compared with that in endometrial and ovarian cancers. By RIA measurements, EMBP was detected in 6/17 mammary cancers (range 11.3-2,660 ng/g tissue) and 2/3 malignant melanomas (618 and 1,240 ng/g), whereas endometrial (n = 6) and ovarian (n = 3) cancers exhibited non-detectable levels. In breast cancer, EMBP-expressing tumours were all estrogen receptor-negative, suggesting an inverse correlation between EMBP and hormone responsiveness of the tumour. Biochemical characterization revealed properties of EMBP in mammary tumours and melanomas almost identical to those for EMBP purified from rat ventral prostate: i.e. surface-charge distribution by Mono Q/FPLC ion-exchange chromatography, a molecular weight of 50,000 by gel filtration, and a subunit composition by Western blot analysis under denaturing conditions. Finally, the EMBP immunoreactivity was confined to the cytoplasm of malignant cells in breast cancer and melanoma sections by immunohistochemical examination. This is the first study that demonstrates EMBP in mammary cancer and malignant melanoma. Our findings suggest that a mechanism for selective uptake of cytotoxic estramustine and estromustine is prevailing in these malignancies and that monitoring of EMBP in biopsy samples will be of value in defining patients who may benefit from Estracyt treatment.

Breast Neoplasms↗
PubMedDate not supplied

In vivo imaging and treatment of human brain tumours utilizing the radiolabelled monoclonal antibody MUC 2-63.

The monoclonal antibody MUC 2-63 identifies a glycoprotein antigen with a molecular weight of 32,000 Dalton present on human malignant gliomas but not detected on normal nerve and brain tissues. This was the prerequisite for these clinical studies with 111In-MUC 2-63 for imaging and 90Y-MC 2-63 for treatment. Seven patients with malignant gliomas, 6 with astrocytomas grade III-IV and 1 with a relapsing astrocytoma grade I-11 received the 111In labelled monoclonal antibody MUC 2-63 for in vivo diagnosis. Six patients had an uptake in the tumour of 0.01 to 0.05% of the MUC 2-63- 111In monoclonal antibody. The patient with the relapsing astrocytoma grade I-II had a negative scan due to a radical operation before the diagnostic dose. All patients received treatment with 90Y-MUC 2-63 intravenously in doses ranging from 146 to 830 MBq. Two patients with relapsing grade III-IV astrocytomas demonstrated clinical improvements and CT changes interpreted as necroses. No serious side-effects were observed in the 5 patients who only received one dose. The two patients who received up to 4 doses experienced grade 3 to 4 leukocyte and thrombocyte toxicity, most likely related to the bone-marrow toxicity by 90Yttrium. These data indicate the potential usefulness of the MUC 2-63 monoclonal antibody for in vivo image on humans with brain tumours and for adjunct treatment after operation and external radiotherapy.

Adult↗
PubMedDate not supplied

Autoradiographic quantitation and anatomical mapping of 125I-galanin binding sites in the rat central nervous system.

The distribution of 125I-galanin binding sites in the rat central nervous system was studied by the use of autoradiography, and the amount of peptide bound was determined by the use of microdensitometry. The amount of 125I-galanin bound in various CNS regions ranged from non detectable to 0.40 pmol per gramme tissue at a concentration of 1.5 nM 125I-galanin. The anatomical mapping revealed high density of binding sites in the telencephalon, where labelling was seen in the entorhinal, perirhinal and piriform cortices, in most septal nuclei, in the amygdala and in the hippocampal formation. In the diencephalon binding sites were densely accumulated in the hypothalamus, including the median eminence and periventricular nucleus as well as in the dorsal and medial thalamic nuclei. In the mesencephalon binding sites were seen in many nuclei including the dorsal raphe nucleus, the periaqueductal central grey and pars compacta of the substantia nigra. The pons/medulla revealed high density of binding sites in the locus coeruleus, parabrachial nuclei and in the dorsal vagal complex, while binding in the spinal cord was seen in laminae I, II and X as well as in the intermediolateral horn. The distribution of 125I-galanin binding sites corresponded well to the localization of the peptide as revealed in several earlier immunohistochemical and radioimmunoassay studies, as well as to several previously reported effects of galanin on central autonomic functions.

Animals↗
PubMedDate not supplied

Quantitation of atherosclerosis in femoral arteriography with ECG gated exposures.

Using a densitometric method introduced in 1977 by Crawford et coll. the volumes of segments of the femoral artery were calculated from two angiographic series in each of 13 patients. ECG gated exposures were used to minimise the error of the method. The reproducibility of the method was found to be better than in a previous study in which ECG gating was not used. The method may therefore be of use in long term angiographic follow-up studies of atherosclerotic lesions, although the impact of different investigation parameters on methodologic precision is still not fully known.

Arteriosclerosis↗
PubMedDate not supplied

Growth of prostatic cancer cells, DU 145, as multicellular spheroids and effects of estramustine.

The human prostatic carcinoma cell line DU 145 was grown as multicellular spheroids in vitro. The volume doubling time during the early exponential growth phase was about 5 days. The saturation volume, in the plateau phase of the growth curve, was in the order of 1.4 mm3. The spheroids developed a central degenerative region surrounded by a 0.1-0.3 mm layer of viable cells. The DU 145 spheroid system is planned to be used as a model in studies on chemotherapy and targeted radiotherapy of micrometastases of prostatic cancer. Some effects of the drug estramustine, EM, a conjugate of estradiol and nornitrogen mustard, were analysed in this introductory study. Tritium-labelled estramustine, 3H-EM, bound both in the viable cell layers and in the degenerative region of the spheroid already after 1 hour of incubation which indicated good penetration. The viable cells bound only low levels of 3H-EM while the degenerative region bound 3H-EM to a higher extent. The amount of bound 3H-EM increased after incubation for 24 hours. The binding was nonspecific since it could not be inhibited by pretreatment with an excess of non-radioactive EM. Furthermore, 3H-EM bound to a similar extent in glioma and colon carcinoma spheroids used for comparison. Incubation of DU 145 spheroids for 24 hours with EM (20 mg/ml) induced a growth delay of 6-7 days and a transient increase in the volume of the extracellular spaces for a few days following the treatment. The results showed that the binding of EM to prostate DU 145 cells growing as spheroids was not specific and that the toxic action was limited. An interesting result was that EM works as an extracellular space expander. This might be exploited in combination treatments with other agents.

Autoradiography↗
PubMedDate not supplied

Estramustine-binding protein (EMBP) content in four different cell lines and its correlation to estramustine induced metaphase arrest.

It is known that estramustine (EM) accumulates in cells at the G2/M-phase and causes metaphase arrest of various cell types. The inhibitory effect is mediated by interaction with microtubule-associated proteins (MAPs) and/or tubulin. Estramustine-binding protein (EMBP) is a secretory protein which has been found in a number of different tumor cells and has been shown to faciliate the uptake of EM into cells. In this study the efficacy of EM in arresting cells at metaphase was studied, using four different human cell lines; the prostatic cancer cell line DU 145, the breast cancer cell line MDA 231, the colon cancer cell line Colon 320, and the urinary bladder cancer cell line RT4. The cells were incubated with EM at a concentration of 10 micrograms/ml for 24 hours. The data reveal an increase in metaphase arrests in the DU 145 and in Colon 320 cell lines. Both of these cell lines were found to contain high amounts of EMBP using a dot-blot assay. The other two cell lines, MDA 231 and RT4 had undetectable intracellular amounts of the protein and exhibited a low increase in metaphase arrests. The cell lines were analysed regarding S-phase fraction with flow-cytometry (FCM) to exclude the growth rate of the cells as a limiting factor. The results from the FCM confirmed the cytogenic analysis, that is a higher percentage of cells were in the G2/M phase in both the DU 145 and Colon 320 cell line compared to MDA 231 and RT4. EM causes mitotic arrest in those cell lines that contain detectable amounts of EMBP.

Antineoplastic Agents, Hormonal↗
PubMedDate not supplied

Neuroendocrine markers; chromogranin, pancreastatin and serotonin in the management of patients with advanced renal cell carcinoma.

A fraction of patients with renal cell carcinoma (RCC) exhibit elevated plasma levels of neuroendocrine (NE) markers, including chromogranin (Cg) A and B, pancreastatin and serotonin. This may suggest neuroendocrine involvement in human RCC. Twenty eight patients (24 men and 4 women) with advanced RCC were included in this study. The ongoing therapy was either tamoxifen, or interleukin-2 (IL-2); alpha interferon and tamoxifen. Plasma analyses of NE markers revealed elevated levels of CgA and serotonin in 28/28 (100%) patients. CgB was elevated in 5/16 (31%) patients, whereas no elevation of pancreastatin was observed in these 16/28 patients. Although the plasma levels of NE markers did not statistically or significantly influence the prognosis of the disease it was observed that patients with elevated NE markers had a less aggressive disease and lived longer than patients with normal or only slightly elevated NE markers. Immunohistochemical analyses of tumour specimens from 10 patients were chromogranin, serotonin and synaptophysin negative, but all were neurone-specific enolase (NSE) positive. The results obtained are of interest. However, extended studies are needed to define the role of these NE markers in the clinical management of patients with RCC.

Adult↗
PubMedDate not supplied

Biological characteristics of adrenocortical carcinoma: a study of p53, IGF, EGF-r, Ki-67 and PCNA in 17 adrenocortical carcinomas.

Adrenocortical carcinoma (ACC) is a rare neoplasm with a poor prognosis. Prognostic factors are needed to identify patients who should be treated aggressively and those for which a less aggressive approach is warranted. As a result of advances within the field of immunohistochemistry, investigations of Ki-67, PCNA, IGF, EGF-r and p53 were performed in 17 ACC. The aim of this study was to clarify the role of Ki-67, PCNA, EGF-r, IGF and p53 in correlation to tumour behaviour and outcome. This retrospective study includes 16 patients, 10 women and 6 men, with a median age of 46 years. Nine tumours were hormonally functioning and 7 were non-functioning. The results obtained revealed that all tumours expressed PCNA and Ki-67 with median values of 59% and 14%, respectively, while p53 was negative in 88%, IGF negative in 82% and EGF-r positive in 94% of the tumours. No correlation was found between p53, IGF, EGF-r and survival rate. There was no interdependence between PCNA and Ki-67, or between PCNA, Ki-67 and the survival rate.

Adrenal Cortex Neoplasms↗