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Biomedical subjects

S Nordling

Publications and source records attributed to S Nordling.

At least 37 records · Page 2Linked to original sources
PubMed2001

Trypsinogen-1, -2 and tumour-associated trypsin-inhibitor in bile and biliary tract tissues from patients with biliary tract diseases and pancreatic carcinomas.

The bile concentrations of trypsinogen-1, -2 and tumour-associated trypsin-inhibitor (TATI) were determined in 23 patients with benign biliary tract disease, two with biliary tract cancer, and in 15 with pancreatic cancer. We also examined the trypsinogen and TATI expression by immunohistochemistry in tissue specimens from biliary tract cancer and non-neoplastic extrahepatic biliary tract. High levels of trypsinogen-1, trypsinogen-2, and TATI occur in bile of most patients. In contrast to the trypsinogens, the levels of TATI were significantly higher in patients with malignant disease than in those with benign diseases (p=0.04). There was no significant correlation between trypsinogen-2 and amylase (r=0.13, p=0.40), indicating that the occurrence of trypsinogen in bile is not a result of reflux of pancreatic fluid into the bile duct. Immunohistochemically, trypsinogen-2 was detected in five and TATI in 12 out of 15 non-neoplastic biliary tract specimens, and in four and seven out of 11 cholangiocarcinomas, respectively. High concentrations of trypsinogen-1, trypsinogen-2 and TATI occur in the bile of patients with non-neoplastic and malignant biliary tract disease and in patients with pancreatic cancer. At least part of the trypsinogen-2 and TATI found in bile appears to be derived from the biliary epithelium itself.

Bile↗
PubMed2001

STn and prognosis in breast cancer.

Sialyl-Tn (STn) is a carbohydrate antigen formed by the premature 2-6 sialylation of N-acetylgalactosamine. It belongs to a family of antigens widely expressed in carcinomas but only to a limited degree in normal tissue. The expression of STn has been associated with prognosis in different tumors. In this immunohistochemical study of 218 patients with invasive stage I-III breast cancer, STn was expressed in 39% of the tumors. High expression of STn correlated with estrogen and progesterone hormone receptor negativity (p = 0.0002 and p = 0.0003, respectively), and marginally with large tumor size (p = 0.04), high S-phase fraction (p = 0.04) and aneuploidy (p = 0.04), but not significantly with node status, grade or age. The patients had a median follow-up of 17 years. The breast-cancer-specific survival rate of patients with STn-negative cancers was higher than that of patients with cancers that expressed STn during the first 5 years of the follow-up (p = 0.013), but the difference between the groups decreased during the long-term follow-up. STn expression seems to be a marker for short-term, but not for long-term breast cancer outcome prediction.

Aneuploidy↗
PubMed2000

[Treatment of depression and cost efficiency. The cost of a tablet is a poor indicator seen from a socioeconomic perspective].

Direct costs for treating depression, i.e. the cost of out-patient and in-patient care together with drug costs, have increased by 55 per cent during the period 1987-1997 in Sweden. Drugs incurred the greatest increase, whereas the cost of in-patient care has decreased. Indirect costs, i.e. sick leave, morbidity and premature mortality due to depression, have also increased during this period. Cost-effectiveness calculations comparing mirtazapine with amitriptyline show that it is less expensive to initiate treatment with mirtazapine, both when direct costs are compared and when indirect costs are included. In a comparison between mirtazapine and fluoxetine, initial treatment with fluoxetine is less expensive with respect to direct cost, but these two alternatives are equivalent when indirect costs are taken into consideration. The price of drug is a poor criterion of resource expenditures and of rational pharmacological therapy in the treatment of depression.

Adrenergic alpha-Agonists↗
PubMed2000

Testicular diffuse large cell lymphoma with tubule preservation--molecular genetic evidence of transformation from previous follicular lymphoma.

Testicular lymphomas usually occur in older men and are mostly diffuse large B-cell lymphomas (DLBL). They may be primary manifestation of lymphoma or represent a relapse of a previous non-Hodgkin's lymphoma. This report details a testicular large cell lymphoma, which was proven to be large cell transformation of a low-grade follicular lymphoma biopsied 8 years earlier. Initially, a 38-year old man was diagnosed with cervical lymphadenopathy, and biopsy was interpreted as reactive follicular hyperplasia; no treatment was given, and the lymphadenopathy resolved spontaneously. Eight years later, the patient underwent surgery for a left testicular mass and gastroscopy for gastric symptoms. The patient died 7 months later with evidence for intra-abdominal and central nervous system lymphoma after a brief but temporary response to M-BACOD chemotherapy. Orchiectomy specimen and gastroscopic biopsy showed diffuse large B-cell lymphoma (CD20+), which infiltrated between well-preserved tubules in the testis. Histological comparison with 20 testicular lymphomas without previous lymphoma showed tubule infiltration in all cases, suggesting that the tubule-preserving infiltration pattern could be a histological marker for secondary lymphoma involvement in testis. On re-examination, the lymph node 8 years prior was verified as follicular, predominantly small, cleaved cell lymphoma with bcl2-positive follicles. The earlier follicular lymphoma and the subsequent diffuse large cell lymphoma were analyzed using polymerase chain reaction and showed identical sequences of the t(14;18) translocation and immunoglobulin heavy chain gene rearrangement. Analysis of the VH-gene sequences from the follicular lymphoma revealed sequence heterogeneity consistent with ongoing mutation. However, the transformed diffuse large cell lymphoma had no intraclonal variation, with the sequence matching with one of the subclones from the low-grade follicular lymphoma. These results confirm that the large cell transformation of follicular lymphoma occurs in a single follicular lymphoma cell. This case also indicates that the selection of the transformed clone can be part of the natural history of disease and can occur without exposure to chemotherapy.

Base Sequence↗
PubMed2000

Expression and characterization of trypsinogen produced in the human male genital tract.

Trypsinogen is a serine proteinase produced mainly by the pancreas, but it has recently been found to be expressed also in several cancers such as ovarian and colon cancer and in vascular endothelial cells. In this study, we found that trypsinogen-1 and -2 are present at high concentrations (median levels, 0.4 and 0.5 mg/L, respectively) in human seminal fluid and purified them to homogeneity by immunoaffinity and anion exchange chromatography. Purified trypsinogen isoenzymes displayed a M(r) of 25 to 28 kd in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. Most of the trypsinogen-1 purified from seminal fluid was enzymatically active whereas trypsinogen-2 occurred as the proform, which could be activated by enteropeptidase in vitro. Immunohistochemically, trypsinogen protein was detected in the human prostate, urethra, utriculus, ejaculatory duct, seminal vesicles, deferent duct, epididymal glands, and testis. Expression of trypsinogen mRNA in the same organs was demonstrated by in situ hybridization. Trypsinogen mRNA was also detected in the prostate and seminal vesicles by reverse transcriptase-polymerase chain reaction and Northern blotting. Isolated trypsin was shown to activate the proenzyme form of prostate-specific antigen. These results suggest that trypsinogen isoenzymes found in seminal fluid are produced locally in the male genital tract and that they may play a physiological role in the semen.

Blotting, Northern↗
PubMed2000

Effects of supplemental alpha-tocopherol and beta-carotene on urinary tract cancer: incidence and mortality in a controlled trial (Finland).

OBJECTIVES: Epidemiological studies have suggested a protective effect of vegetables and fruits on urinary tract cancer but the possible protective nutrients are unknown. We studied the effect of alpha-tocopherol (a form of vitamin E) and beta-carotene supplementation on urinary tract cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. METHODS: A total of 29,133 male smokers aged 50-69 years from southwestern Finland were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or a placebo daily for 5-8 years (median 6.1 years). Incident urothelial cancers (bladder, ureter, and renal pelvis; n = 169) and renal cell cancers (n = 102) were identified through the nationwide cancer registry. The diagnoses were centrally confirmed by review of medical records and pathology specimens. The supplementation effects were estimated using a proportional hazards model. RESULTS: Neither alpha-tocopherol nor beta-carotene affected the incidence of urothelial cancer, relative risk 1.1 (95% confidence interval (CI) 0.8-1.5) and 1.0 (95% CI 0.7-1.3), respectively, or the incidence of renal cell cancer, relative risk 1.1 (95% CI 0.7-1.6) and 0.8 (95% CI 0.6-1.3), respectively. CONCLUSION: Long-term supplementation with alpha-tocopherol and beta-carotene has no preventive effect on urinary tract cancers in middle-aged male smokers.

Aged↗
PubMed1999

Concomitant gastrin and ERBB2 gene amplifications at 17q12-q21 in the intestinal type of gastric cancer.

Our recent studies using comparative genomic hybridization showed that gain or amplification at the 17q12-q21 region is very common in the intestinal type of gastric cancer. Here, we describe a fluorescence in situ hybridization study with gastrin (GAS)-specific and ERBB2-specific probes on ten specimens of gastric carcinoma that, by using comparative genomic hybridization, showed 1) DNA copy number gain or amplification at 17q12-q21, a region known to harbor the GAS and ERBB2 genes (four cases); 2) gain of the entire chromosome 17 (three cases); or 3) normal copy number of chromosome 17 (three cases). GAS and ERBB2 protein expression was studied by Western immunoblotting from gastric cancer cell lines with or without gain at 17q12-q21 as well as a breast cancer cell line with ERBB2 amplification. Our results showed that simultaneous amplification of both GAS and ERBB2 was four- to ninefold in the tumors with the 17q12-q21 amplification. Both genes were amplified in the same nuclei, and the hybridization signals were localized to the same region of the nucleus. Overexpression of GAS and ERBB2 was observed by Western immunoblotting only in the gastric cancer cell line with gain at 17q12-q21. The ERBB2 amplification is also a recurrent change in breast cancer. To investigate whether the GAS amplification is unique in gastric cancer, fluorescence in situ hybridization analysis was performed on 40 breast cancer cell lines. The ERBB2 amplification was observed in 11 cell lines, but none of the lines showed the GAS amplification. This indicates that the formation of an amplicon, in which both the GAS and the ERBB2 genes are amplified, might be unique in gastric cancer, especially in its intestinal type, and that simultaneous amplification of both genes is important to the tumorigenesis of intestinal gastric cancer. We demonstrate here for the first time that a gene of a physiological hormone is amplified in tumors that originate from cells that normally secrete the hormone.

Breast Neoplasms↗
PubMed1999

Deletions at 14q in malignant mesothelioma detected by microsatellite marker analysis.

Previous molecular cytogenetic studies by comparative genomic hybridization (CGH) on primary tumours of human malignant mesothelioma have revealed that loss of genetic material at chromosome 14q is one of the most frequently occurring aberrations. Here we further verify the frequency and pattern of deletions at 14q in mesothelioma. A high-resolution deletion mapping analysis of 23 microsatellite markers was performed on 18 primary mesothelioma tumours. Eight of these had previously been analysed by CGH. Loss of heterozygosity or allelic imbalance with at least one marker was detected in ten of 18 tumours (56%). Partial deletions of varying lengths were more common than loss of all informative markers, which occurred in only one tumour. The highest number of tumours with deletions at a specific marker was detected at 14q11.1-q12 with markers D14S283 (five tumours), D14S972 (seven tumours) and D14S64 (five tumours) and at 14q23-q24 with markers D14S258 (five tumours), D14S77 (five tumours) and D14S284 (six tumours). We conclude from these data that genomic deletions at 14q are more common than previously reported in mesothelioma. Furthermore, confirmation of previous CGH results was obtained in all tumours but one. This tumour showed deletions by allelotyping, but did not show any DNA copy number change at 14q by CGH. Although the number of tumours allelotyped was small and the deletion pattern was complex, 14q11.1-q12 and 14q23-q24 were found to be the most involved regions in deletions. These regions provide a good basis for further molecular analyses and may highlight chromosomal locations of tumour suppressor genes that could be important in the tumorigenesis of malignant mesothelioma.

Adult↗
PubMed1999

Sialyl Tn is a frequently expressed antigen in colorectal cancer: No correlation with patient prognosis.

Immunohistochemical expression of sialyl Tn antigen (STn), previously claimed to be a prognostic factor in colorectal cancer, was evaluated in 239 patients with colorectal adenocarcinoma. Formalin-fixed, paraffin-embedded specimens were stained with the monoclonal antibody C1282. STn immunoreactivity was seen in 189 of 239 tumors (79%). There was no significant correlation between STn immunoreactivity and Dukes stage, tumor location, histological type or gender. However, STn was significantly more often expressed in younger patients. There was so significant difference in survival between STn-negative patients (median survival 68 months) and STn-positive patients (median survival 79 months). In a Cox multivariate analysis, Dukes stage was the strongest predictor of outcome, followed by the age of the patient, whereas STn did not provide any prognostic information.

Adenocarcinoma↗
PubMed1999

Among numerous DNA copy number changes, losses of chromosome 13 are highly recurrent in plasmacytoma.

Chromosomal imbalances were studied by comparative genomic hybridization (CGH) on 27 specimens from 24 patients with plasmacytoma. All the specimens exhibited DNA copy number changes (mean, 7.7 aberrations/tumor; range, 2-15). The most recurrent change involved losses at 13q, found in 19 out of 24 patients. Other frequent losses were at 1p (42%), 14q (33%), X (33%), 8p (25%), and 6q (25%). Gains were frequent at 19p (58%), 9q (58%), 1q (58%), 7p (42%), 11q (38%), 15 (33%), 6p (25%), 8q (25%), and 5p (21%). High-level copy number increases were found at 1q, 5, 7, 8q, 9q, 11q, 15, and 19. The findings of highly recurrent chromosomal imbalances in plasmacytomas confirm the analytical power of CGH to detect chromosomal abnormalities in malignancies characterized by low mitotic activity. Our most striking finding, the losses in chromosome 13, provides a basis to investigate the role of the 13q loss in the tumorigenesis and progression of plasmacytoma and to evaluate the prognostic significance of this loss.

Adult↗
PubMed1999

Measurement of the complex between prostate-specific antigen and alpha1-protease inhibitor in serum.

BACKGROUND: Prostate-specific antigen (PSA) occurs in serum both free and in complex with protease inhibitors. The complex with alpha1-antichymotrypsin (ACT) is the major form in serum, and the proportion of PSA-ACT is higher in prostate cancer (PCa) than in benign prostatic hyperplasia (BPH). PSA also forms a complex with alpha1-protease inhibitor (API) in vitro, and the PSA-ACT complex has been detected in serum from patients with prostate cancer. The aim of the present study was to develop a quantitative method for the determination of PSA-API and to determine the serum concentrations in patients with PCa and BPH. METHODS: The assay for PSA-API utilizes a monoclonal antibody to PSA as capture and a polyclonal antibody to API labeled with a Eu-chelate as a tracer. For calibrators, PSA-API formed in vitro was used. Serum samples were obtained before treatment from 82 patients with PCa, from 66 patients with BPH, and from 22 healthy females. RESULTS: The concentrations of PSA-API are proportional to the concentrations of total PSA. PSA-API comprises 1.0-7.9% (median, 2.4%) of total immunoreactive PSA in PCa and 1.3-12.2% (median, 3.6%) in BPH patients with serum PSA concentrations >4 microgram/L. In patients with 4-20 microgram/L total PSA, the proportion of PSA-API serum is significantly higher in BPH (median, 4.1%) than in PCa (median, 3. 2%; P = 0.02). CONCLUSIONS: The proportion of PSA-API in serum is lower in patients with PCa than in those with BPH. These results suggest that PSA-API is a potential adjunct to total and free PSA in the diagnosis of prostate cancer.

Electrophoresis, Polyacrylamide Gel↗
PubMed1998

Clinical relevance of p53 index and expression of proliferating cell nuclear antigen and Ki-67 in gastric cancer.

The prognostic value of the immunohistochemical expression of p53 protein, proliferating-cell nuclear antigen (PCNA) and Ki-67 antigen was evaluated in a series of 116 stage I-II gastric cancer patients. The staining for p53 protein (staining frequency and intensity) in malignant cells was expressed as a p53 index. Similarly, the staining frequency and intensity for PCNA and Ki-67 were evaluated. The p53 index was independent of the stage and differentiation grade, but significantly related to DNA ploidy, S-phase fraction and mitotic activity. A high p53 index was a sign of inferior survival, compared to a low or intermediate index. p53-negative tumours were also associated with poor survival. In a multivariate analysis, only the depth of tumour infiltration and the presence of nodal metastases were independent prognostic factors in stage I-II gastric cancer. PCNA expression and Ki-67 antigen expression were not related to the stage, ploidy, proliferative activity or p53 expression, and they had no impact on survival. The results indicate that p53 protein expression may be of prognostic significance in gastric cancer, while PCNA and Ki-67 antigen expression have no predictive value.

Adult↗
PubMed1998

Molecular pathological analysis of testicular diffuse large cell lymphomas.

The molecular pathology of 20 lymphomas, which presented as testicular masses in patients with no evidence of previous lymphoma, was analyzed. These lymphomas occurred in men with a median age of 69 years (range, 37 to 87 years). Nine of the 14 patients with follow-up died of lymphoma (median survival, 12 months). All cases were diffuse large B-cell lymphomas that were positive for CD20 and commonly showed plasmacytoid differentiation (10 of 20 cases). Three cases were Burkitt's-like large cell lymphomas. Infiltration by lymphoma in the seminiferous tubules was seen in most cases. All lymphomas were negative for human herpesvirus 8 and Epstein-Barr virus by 35 cycles of polymerase chain reaction (PCR), suggesting that these viruses are not involved in the pathogenesis of primary testicular diffuse large B-cell lymphomas (DLBCL). PCR-based studies for t(14;18) and t(11;14) translocations, commonly seen in follicular and mantle-cell lymphomas, were negative in all cases. Nucleotide sequences of the V-D- and J segments of the immunoglobulin heavy chain gene (IgH) rearrangements obtained in 12 cases after PCR amplification were analyzed and compared with known germlines. The frequency of VH-family use in testicular DLBCL was similar to that reported for normal peripheral blood lymphocytes and follicular lymphomas. This contrasts with the previously published findings of preferential use of the VH3- or VH4-family by nodal DLBCL. Comparison with the published germlines showed a low similarity index in most of the cases, suggesting the presence of extensive somatic mutations. Ongoing mutation, as indicated by intraclonal variation in IgH sequence, was observed in all sequenced cases, suggesting direct antigen stimulation, which represents another difference between primary testicular and nodal DLBCL. Our results suggest that testicular lymphomas represent a subset of DLBCL that differs from their nodal counterparts in several respects. Their histological and molecular features show some similarities to those seen in marginal zone (MALT) lymphomas.

Adult↗
PubMed1998

Presence of high-level DNA copy number gains in gastric carcinoma and severely dysplastic adenomas but not in moderately dysplastic adenomas.

Our aim was to investigate the presence of DNA copy number changes in gastric adenomas and to identify the changes that may play a role in gastric carcinogenesis. DNA copy number changes in 16 patients with gastric adenoma and in 22 tumors from patients with intestinal type gastric carcinomas were studied by using comparative genomic hybridization. DNA copy number changes were found in 44% of the adenoma cases and in 86% of the intestinal type gastric carcinomas. On average, gains were more common than losses (0.9 vs. 0.5 in adenomas and 4.1 vs. 1.8 in carcinomas). In adenomas, the most common gains involved chromosome 8 in 3 cases, and gain of chromosome 7 and 20q was detected in 2 cases. The most frequent losses were observed at 5q (three times). Only adenomas with severe dysplasia showed high-level amplifications that were detected at chromosome 13, 17cen-q22, and 20q12-ter. In gastric cancer, the most common gains were detected at 20q (55%), 17q12-q21 (41%), and 8q (41%), and the most common losses were detected at 18q (41%) and 4q (32%). High-level amplifications were observed at 20q (3 tumors), 17cen-q21 (3 tumors), 2p (1 tumor), and 18q (1 tumor). These findings suggest that the progression of dysplasia is associated with higher levels of DNA copy number increase (e.g., the gains at 17q and 20q), which were typically observed in the intestinal type gastric cancer. Furthermore, the results support the hypothesis that adenoma precedes cancer.

Adenocarcinoma↗
PubMed1998

Expression of tenascin-C in intraductal carcinoma of human breast: relationship to invasion.

Tenascin-C (Tn-C) is an extracellular matrix glycoprotein that appears in areas of epithelial-mesenchymal interaction during fetal development and in neoplasia. The immunohistochemical expression of Tn-C and its relationship to histology, nuclear grade, microinvasion, oestrogen (ER) and progesterone receptors (PR), and to cell proliferation measured by Ki-67 expression were studied in 89 intraductal breast carcinomas (DCIS). Periductal Tn-C was noted in 87% and stromal Tn-C in 25% of the tumours. Stromal expression was associated with moderate to strong periductal expression and microinvasion. Periductal expression was associated with comedo-type, nuclear grade, microinvasion, Ki-67 expression, and lack of PR. The distribution of Tn-C was compared in DCIS and in the intraductal component from another series of small axillary node-negative invasive breast carcinomas (n = 44). Tn-C was present in the stroma of pure DCIS in 25% and in the intraductal component of the other series in 82%. Thus, stromal or moderate to strong periductal Tn-C expression in DCIS may relate to early invasion. DCIS with weak periductal or missing Tn-C expression may be a subgroup with benign behaviour.

Adult↗
PubMed1998

Mitotic rate and S-phase fraction as prognostic factors in stage I cutaneous malignant melanoma.

Clinical data from 369 patients with clinical stage I cutaneous malignant melanoma treated in Kuopio University Hospital district between 1974 and 1989 with a mean follow-up of 6.4 years were analysed. Clinical parameters, histology, DNA index, S-phase fraction (SPF) and mitotic indices [mitotic activity index (MAI) and volume-corrected mitotic index (M/V index)] were correlated with the outcome of the disease to establish their value as predictors of stage I cutaneous malignant melanoma. In univariate survival analyses, bleeding, gender, tumour thickness, level of invasion according to Clark, TNM category, MAI, M/V index and SPF were the most significant predictors of recurrence-free (RFS) and overall survival. In Cox's multivariate analysis, tumour thickness (P = 0.0021), bleeding (P = 0.0106) and M/V index (P = 0.0058) predicted poor RFS in the 259 patients available for the analysis. Poor overall survival was predicted by MAI (P = 0.0002), bleeding (P = 0.004), SPF (P = 0.009) and male gender (P = 0.034). The present results indicate that mitotic activity index (MAI), volume-corrected mitotic index (M/V index) and S-phase fraction (SPF) are important prognostic factors in addition to the well-established Breslow thickness in stage I cutaneous malignant melanoma.

Adult↗
PubMed1998

Comparison of DNA copy number changes in malignant mesothelioma, adenocarcinoma and large-cell anaplastic carcinoma of the lung.

The differential diagnosis of mesothelioma, primary adenocarcinomas and pleural metastases frequently causes problems. We have used the comparative genomic hybridization (CGH) technique on 34 malignant mesotheliomas and 30 primary lung carcinomas (adenocarcinoma, including bronchoalveolar carcinoma and large-cell anaplastic carcinoma) to compare their copy number changes and to evaluate the use of CGH to distinguish between these two types of tumour. In mesothelioma, gains of genetic material occurred as frequently as losses, whereas gains predominated over losses in carcinoma. In mesothelioma, the most frequent changes were losses in 4q, 6q and 14q and gains in 15q and 7p, whereas gains in 8q, 1q, 7p, 5p and 6p were the most common changes in carcinoma. Amplification of KRAS2 was detected in two adenocarcinomas by Southern blot analysis. CGH showed gains in 12p in the same tumours. Statistically significant differences between the two types of tumour were detected in chromosomes X, 1, 2p, 4, 8q, 10q, 12p, 14q, 15q and 18q. When comparing the frequency of gains and losses between mesothelioma and lung carcinoma using discriminant analysis, the sensitivity of CGH to differentiate mesotheliomas from lung carcinomas was 81% and the specificity 77%. The differences in DNA copy number changes between the two types of tumour suggest that they are genetically different tumour entities. Although CGH cannot be used as a definitive discriminatory method, we were able to distinguish between mesothelioma and lung carcinoma in a large proportion of the abnormal cases.

Adenocarcinoma↗