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Biomedical subjects

S Linder

Publications and source records attributed to S Linder.

155 records · Page 9Linked to original sources
PubMedDate not supplied

Chronic daily headache in children and adolescents: current status and recommendations for the future. Pediatric Committee of the American Association for the Study of Headache.

The Pediatric Committee of the American Association for the Study of Headache was created in 1994 to develop a plan for comprehensively addressing global issues of headache in childhood. It was the impression of clinicians and researchers with an interest in childhood headaches that a clearer focus was needed to facilitate progress in the study and management of pediatric headache. It was further felt that approaches to treatment and outcomes, as well as assessment and classification schema for pediatric patients needed to be examined separately. The goal of the committee is to integrate anecdotal, clinical, and research expertise into a plan for addressing headaches in the pediatric population in the future. During the last 5 years, substantial attention has been devoted to chronic daily headache, primarily in adult populations. It is the purpose of this paper to review the literature of chronic daily headache in children, and propose areas for further exploration, given the recent emergence of interest in this diagnostic entity.

Adolescent↗
PubMedDate not supplied

Angiostatin fragments in urine from patients with malignant disease.

Angiostatin, a family of fragments originating from the NH2-terminal portion of plasminogen, has been described as a potent inhibitor of angiogenesis. In order to examine to what extent angiostatin can be detected in cancer patients, urine was collected from 117 patients with different types of malignancies and subjected to Western blot analysis, utilizing antibodies raised against "kringles" 1-3 in plasminogen. A heterogeneous mixture of fragments was observed, with patterns that also varied between patients. Angiostatin fragments were quantified by densitometric scanning. The concentrations were 27 +/- 75 (SD) micrograms L-1 (range, 1-565 micrograms L-1) in urine from cancer patients, as compared to 3 +/- 2 (SD) micrograms L-1 (range, 1-10 micrograms L-1) in urine from healthy individuals. Thirty-three patients (28%) had elevated levels using a cut off level at 15 micrograms L-1 (clearly above the highest level obtained among control subjects). NH2-terminal amino acid sequence analysis of purified angiostatin fragments from one patient showed a heterogeneous pattern, but were consistent with the region between the preactivation peptide in plasminogen and "kringle" 1, as expected. Several of the patients with urinary angiostatin showed signs of poor kidney function. We conclude that angiostatin can be detected in urine from cancer patients, but at present, the clinical significance of this finding is unclear.

Albuminuria↗
PubMedDate not supplied

Laminin-5 as a predictor of invasiveness in cancer in situ lesions of the larynx.

Squamous epithelial cancer in situ (CIS) of the upper aerodigestive tract is a histopathologically well-defined condition. There is yet no reliable way to predict whether a CIS lesion will progress to invasive cancer, remain stable or regress. In the search for markers able to foretell clinical outcome, we performed immunohistochemical staining with a polyclonal antibody against recombinant gamma 2 chain of laminin-5 in 33 laryngeal CIS lesions. All six CIS lesions which progressed to invasive cancer, within a follow-up time of 5 years, were laminin-5 positive (100%), whereas only 10 out of 27 lesions which did not progress were positive (37%) (p < 0.01). Our data showed that a positive laminin-5 laryngeal CIS lesion indicates a high risk for progression to invasive cancer.

Adult↗
PubMedDate not supplied

Endoscopic therapy in primary sclerosing cholangitis: outcome of treatment and risk of cancer.

BACKGROUND/AIMS: Primary sclerosing cholangitis is a cholestatic liver disease characterized by multifocal strictures in the intra- and extrahepatic biliary tree. Dominant strictures may arise in the extrahepatic bile ducts, and in these circumstances, endoscopic therapy has been introduced to relieve cholestasis and perhaps also delay the development of liver cirrhosis. The experience of endoscopic treatment at this point in time is limited and the long-term benefit is not clear. Neoplastic transformation in primary sclerosing cholangitis is unpredictable, which is illustrated in the present study along with an evaluation of the efficacy of endoscopic treatment. METHODOLOGY: Endoscopic retrograde cholangiopancreatography was performed in 25 patients with primary sclerosing cholangitis. In 15 there were dominant strictures in the hilum of the liver and/or the distal bile duct and these patients were treated by dilation and/or endoprostheses. Four patients in the treatment group had just cholestatic biochemical test results and 11 were symptomatic. RESULTS: Endoscopic therapy was technically successful in all 15 patients. In 43 sessions, 5 patients were treated by dilation, 2 with endoprostheses, and 8 by both methods. Improvement was achieved radiologically in 12 patients, clinically in 8, and according to liver function tests in 7. Therapy was complicated by cholangitis in 5 patients. Complications were mild and there was no mortality related to the procedure. However, 6 patients in the treatment group died, 5 of cholangiocarcinoma and 1 of colon cancer. CONCLUSIONS: Endoscopic therapy in primary sclerosing cholangitis is indicated in selected patients. The cancer incidence is high, not least in patients with deteriorating disease. It is important to find techniques for identifying patients at risk in order to perform liver transplantation before malignant transformation.

Adult↗
PubMedDate not supplied

Immunohistochemical expression of extracellular matrix proteins and adhesion molecules in pancreatic carcinoma.

BACKGROUND/AIMS: Carcinoma invasion and metastasis in general involve multiple steps including dynamic changes in the composition and structure of extracellular matrix proteins and cell surface receptors. In the present study, the usually highly invasive carcinoma of the pancreas was investigated regarding the expression of various extracellular matrix proteins and their corresponding integrin receptors, as well as E-cadherin. METHODOLOGY: Phenotypic expression of various markers was investigated immunohistochemically in frozen sections of 16 pancreatic carcinomas and normal pancreatic tissue. RESULTS: An irregular and discontinuous deposition of type IV collagen and laminin in the basement membrane was found in cancer tissue and a pronounced desmoplastic reaction with deposition of type I, type III, and type IV collagen in the tumor stroma. In contrast, the noninvolved pancreas showed an intact basement membrane and a sparse stroma. The collagen type IV and laminin receptors alpha 2, alpha 3, and beta 1 integrin subunits were expressed on pancreatic cancer cells but not the alpha 6 integrin subunit normally present on epithelial cells, suggesting anchorage independence of the carcinoma cells. An increased capacity for cancer cell motility was suggested by the abundant expression of the "antiadhesive" extracellular matrix proteins, tenascin and vitronectin close to the cancer cells, and the expression of cell surface receptors such as alpha v (vitronectin-binding). Expression of the alpha 4 integrin subunit was also increased on cancer cells. CONCLUSIONS: The distribution of extracellular matrix proteins and the cell surface immune phenotype differed in pancreatic carcinoma as compared to normal pancreatic tissue. The present findings substantiate the notion that disseminated growth of highly malignant carcinomas of the pancreas reflects an invasive interaction of the tumor cells with extracellular matrix proteins of a well-established stroma. Similar findings were observed regardless of tumor histology and patient survival time.

Adenocarcinoma↗
PubMedDate not supplied

Prognostic importance of the uPa/PAI-1 complex in breast cancer.

The complex between urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 (plasminogen activator inhibitor 1) has been prognostically evaluated in patients with breast cancer. The concentrations of uPA antigen, PAI-1 antigen and the uPA/PAI-1 complex were analysed in extracts from breast cancer tumours from 233 patients (median follow-up of patients: 71months). The uPA/PAI-1 complex typically constituted about 5% of the uPA antigen (total uPA). The concentration of complex was found to correlate more strongly to the concentration of PAI-1 (r = 0.72; p < 0.0001) than to the concentration of uPA (r = 0.55: p < 0.0001). Interestingly, in this material the uPA/PAI-1 complex (using an optimised cutoff level of 0.22 ng microg(-1) DNA) had a stronger prognostic value than optimised cut-off valuesfor uPA or PAI-1. The data suggest that activation of prourokinase within the tumour, which is a prerequisite for the formation of the uPA/PAI-1 complex, is of better prognostic value than the production of prourokinase or PAI-1 in the breast cancer tumour.

Adult↗
PubMedDate not supplied

[Measuring precision in determining the length of restriction fragments within the scope of DNA analysis].

Because of the measurement error that is known from the length determination of restriction fragments during DNA analysis, it is necessary to determine the precision by which identical DNA can be evaluated. Besides the collection of frequency data from a certain population this is one of the basic prerequisites to calculate the likelihood ratio of an established polymorphism. By multiple measurement of restriction fragments from different persons indicated by the probes MS1, MS31, MS43A, g3 and YNH24 on different blots the within-laboratory variation was determined in the complete separation area from 1 to 19 kb. The values were compared to procedures used by other laboratories.

Blood Group Antigens↗
PubMedDate not supplied

Expression of CDK inhibitor genes in immortalized and carcinoma derived breast cell lines.

The expression of the CDK inhibitor (CDI) genes p15(INK4B), p16(INK4A), p18 and p21Cip1 was examined in immortalized, non-tumorigenic cell lines derived from human breast epithelium, and in breast carcinoma derived lines. An increase in p16 expression, suggesting loss of pRb function, was recorded in two immortalized lines, and complete absence of p16 mRNA was observed in the third. In contrast, high levels of p21Cip1 mRNA were found in two immortalized lines. In addition to differences in p16 and p21Cipl, variations in the expression of p15 and p18 mRNA were observed between different cell lines. Immortalized A1N4 and HBL100 cells, as well as ER+, MCF-7 carcinoma cells, expressed high levels of p15 mRNA. A1N4, HBL100 cells and highly malignant ER MDA-MB-231 cells expressed high levels of p18 mRNA. Inhibition by genistein indicated that p18 mRNA expression was dependent on cellular tyrosine kinases in these cells. We conclude that the pattern of p15 and p18 mRNA expression was distinct from that of p16 and p21Cip1, suggesting different modes of regulation.

Benzo(a)pyrene↗
PubMedDate not supplied

The Ras farnesylation inhibitor BZA-5B increases the resistance to cisplatin in a human melanoma cell line.

Ras proteins have been implicated in transducing cellular responses to DNA damaging agents. We used BZA-5B, an inhibitor of Ras-farnesylation, to examine the role of Ras in cellular sensitivity to cisplatin. A human melanoma cell line (224) with a Gln61Arg mutation in N-ras was used for these studies. We report that BZA-5B treated cells show an increased resistance to cisplatin. BZA-5B treatment decreased the number of cells showing in situ DNA fragmentation and increased cell viability and clonogenic survival after cisplatin treatment. Further experiments showed that cisplatin induction of the immediate early genes c-jun and p21cip1 was not affected by BZA-5B. Finally, we show that cisplatin causes only weak activation of Jun N-terminal kinase (JNK) in a human melanoma cell line. We conclude that inhibition of Ras function decreases the sensitivity of human melanoma cells to cisplatin-induced cell death.

Alkyl and Aryl Transferases↗
PubMedDate not supplied

Independent expression of serum vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients with carcinoma and sarcoma.

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were quantified in the sera of 100 patients with sarcoma, head and neck carcinoma, oesophageal carcinoma, mesothelioma and lung carcinoma. VEGF and bFGF levels were generally higher in the sera of the tumor patients compared to the sera of healthy control subjects. Interestingly, VEGF and bFGF levels were generally not elevated in the same sera (p < 0.01), and covariation of the VEGF and the bFGF levels was only rarely observed during progressive disease, arguing for actual independence of factors. Very high levels of VEGF (668 pg/ml, n = 12) were observed in patients with mesothelioma, whereas bFGF levels were not increased in these patients. Our data suggest that VEGF levels increase with tumor progression and may be a useful marker for clinical monitoring of sarcoma and carcinoma patients.

Adult↗