Biomedical subjects

C K Høgdall

Publications and source records attributed to C K Høgdall.

At least 19 recordsLinked to original sources

PubMed2006

Tetranectin in cerebrospinal fluid of patients with multiple sclerosis.

OBJECTIVE: Tetranectin (TN) is a glycoprotein and C-type lectin thought to play a prominent role in tissue remodelling. The aim of this study was to determine the TN serum and cerebrospinal fluid (CSF) concentration in patients with multiple sclerosis (MS) and controls. MATERIAL AND METHODS: Two-hundred-and-four patients, divided into four diagnostic groups, i.e. definite MS (n = 76), possible onset symptoms of MS (n = 48), other non-inflammatory neurological diseases (n = 61) and other inflammatory neurological diseases (n = 19) and 47 controls with no history of neurological disease were analysed for TN in serum and CSF using a polyclonal sandwich ELISA. RESULTS: All tested groups, e.g. definite MS, possible onset symptoms of MS, other neurological disease, both inflammatory and non-inflammatory, had decreased concentrations of TN in the CSF compared to the concentrations in controls. The quotient of TN in CSF divided by the concentration in serum (QTN) correlated significantly with the same quotient of albumin (QALB), was significantly correlated with the same quotient of albumin QALB. To account for differences in blood brain barrier permeability, we calculated a TN-index defined as: TN-index = QTN/QALB. QTN was significantly decreased in all groups compared to that in controls. However, in definite MS and patients with first attack of MS, the TN-index was not significantly different from that of controls. In contrast, other neurological diseases, both inflammatory and non-inflammatory, were associated with a decreased TN-index. CONCLUSION: These results indicate that TN may play a role in neurological diseases and may serve as a diagnostic aid in MS.

Adult↗

PubMed2006

Do risk factors for epithelial ovarian cancer have an impact on prognosis? Focus on previous pelvic surgery and reproductive variables.

OBJECTIVES: The prognostic impact of risk factors for ovarian cancer development is sparsely explored, but previous sterilisation has been shown to have a negative impact on survival. METHODS: Ovarian cancer cases were from the Danish MALOVA study. Information on previous pelvic surgery as well as reproductive variables was obtained from a personal interview conducted closely after primary surgery. Cox regression models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for ovarian cancer specific death in relation to previous pelvic surgery and reproductive variables including lifetime number of ovulation years. RESULTS: A total of 295 women with Stage III ovarian carcinomas were identified and followed to death or for a median of 7.3 years (range 5.4-9.5 years). Previously sterilised or hysterectomised women seemed to have a slightly decreased risk of ovarian cancer death (HR = 0.62; 95% CI: 0.36-1.08 and HR = 0.82; 95% CI: 0.55-1.21), although none of these associations reached statistical significance. The prognostic impacts of the individual reproductive variables followed the same pattern as the impact of the variables on ovarian cancer development, although significance was only reached for age at menarche (HR = 0.91 per year; 95% CI: 0.84-0.99). By accumulation of the possible minor effects of the reproductive variables in calculation of the total lifetime number of ovulation years, we found that survival decreased significantly with increasing number of ovulations (HR = 1.53 per 10 years; 95% CI: 1.09-2.14). CONCLUSION: Increasing lifetime number of ovulations was a negative prognostic factor for ovarian cancer specific survival. Previous sterilisation or hysterectomy seemed to be associated with improved survival.

Adenocarcinoma↗

PubMed2005

Increased risk of ovarian cancer in integrin beta3 Leu33Pro homozygotes.

We previously demonstrated that integrin beta(3) Leu33Pro homozygotes have an increased risk of cancer, possibly most pronounced for ovarian cancer. We now test the latter hypothesis in case-control and prospective studies. We genotyped 463 Danish women with ovarian cancer, and 4291 women from the Danish general population. Calculation of odds ratios by conditional logistic regression was performed in the case-control study (n = 463 + 3543), and of ovarian cancer incidence, log-rank statistics and hazard ratios by Cox regression in the prospective study (n = 4291) with 9.5-year follow-up. In the case-control study matched for age and marital status, the odds ratio for ovarian cancer in homozygotes versus non-carriers was 1.6 (95% confidence interval: 1.0-2.6). In the prospective study with 28 incident ovarian cancers, non-carriers and homozygotes had incidences of 7 (4-11) and 30 (10-92) per 10 000 person-years (log-rank P = 0.02). The age-adjusted hazard ratio for ovarian cancer in homozygotes versus non-carriers was 3.9 (1.1-13). Risk of ovarian cancer did not differ between heterozygotes and non-carriers in either study. Integrin beta(3) Leu33Pro homozygotes have an increased risk of ovarian cancer.

Adult↗

PubMed2001

Alpha-fetoprotein in plasma and serum of healthy adults: preanalytical, analytical and biological sources of variation and construction of age-dependent reference intervals.

Alpha-fetoprotein (AFP) is a tumor marker for hepatomas and germ cell tumors, and the serum concentration has prognostic significance in other diseases. We examined the normal serum concentration of AFP in adults and sources of variation in the immunochemical variation of AFP. The serum concentration of the tumor marker alpha-fetoprotein (S-AFP) was log-normally distributed in 284 adult blood donors. S-AFP increased with age (p < 10(-7)), whereas no gender-related difference was found. Reference intervals (95-interpercentile) were constructed for persons < or =40 years (0.60-9.30 kIU/L) and >40 years (1.40 12.60 kIU/L). The concentration of AFP was significantly, albeit slightly, higher in serum than in plasma, whereas hemolysis, pretreatment with KCl and food intake did not influence S-AFP. S-AFP only changed 6% when measured twice 2 months apart (p=0.04). Three enzyme immunoassays, using three different anti-AFP monoclonal antibodies for detection, were compared and two assays gave S-AFP values significantly higher, 2.8% (p=0.03) and 19.0% (p<10(-4)), than the other assay. Thus, the choice of antibody may influence the result of immunochemical concentration determination. This can be explained by the existence of conformational variants of AFP with different antibody reactivities, and calls for careful standardization of monoclonal antibodies used in assays for AFP. With broad population reference ranges and slight intra-personal variation, the most effective reference range for S-AFP is previous values obtained in the same person.

Adult↗

PubMed2000

Predictive values of serum tumour markers tetranectin, OVX1, CASA and CA125 in patients with a pelvic mass.

Our objective was to compare the predictive value of the well-established tumour marker CA125 with the newer tumour markers tetranectin (TN), OVX1 and CASA in distinguishing benign and malignant pelvic masses in women. Participants included 185 women, 19 years or older, with a pelvic mass planned for surgical exploration. Significantly different CA125 levels were found between benign tumours and localised ovarian cancer (OC), advanced OC and other non-OCs. Significantly different TN levels were found between benign tumours and advanced OC (stage III/IV), between benign tumours and other cancers and between all OCs and other cancers. For CASA, significant differences were found between benign tumours and all OCs as well as advanced OC. No significant differences could be demonstrated for OVX1. Significant correlations for the 44 OC patients were found between CA125, TN and CASA. No significant correlations were found for OVX1, possibly because of the method used for collection and handling of serum samples. None of the new markers had any additional predictive value compared to CA125. TN and CASA levels correlated with FIGO stage and could be used to discriminate between benign and advanced OC. However, in comparison to the performance of CA125, the additional discriminative value of TN and CASA was minor.

Adult↗

PubMed2000

Alpha-fetoprotein in human fetal cerebrospinal fluid.

Alpha-fetoprotein (AFP) is a fetal glycoprotein. It has been ascribed a regulatory function of growth factor responses and immune functions. The concentrations of AFP and albumin (ALB) are highly variable in fetal serum and CSF and change with gestational age. The AFP index=[AFP(CSF)/AFP(SERUM)]/[ALB(CSF)/ALB(SERUM)] was determined in six normal fetuses at gestational age 17-23 weeks and found to be independent of gestational age and close to unity, mean 0.90+/-0.11 (S.D.). The ratio of CSF-serum concentrations of AFP and ALB both decreased significantly (p<0.05) with gestational age. The mean fraction of AFP being non-reactive with concanavalin A was 1.7% in serum and 1.9% in CSF, suggesting a common hepatic origin of AFP in both compartments. In conclusion, the concentration of AFP in CSF seems to be determined largely by the serum-CSF concentration gradient in normal fetuses. This finding, combined with the remarkable constancy of the AFP index compared to the highly variable absolute concentrations of AFP in both serum and CSF should make the AFP index the marker of choice when analyzing for intrathecal AFP synthesis during development and in pathological conditions.

Concanavalin A↗

PubMed2000

The prognostic value of pretherapeutic tetranectin and CA-125 in patients with relapse of ovarian cancer.

OBJECTIVE: The aim of the study was to examine the prognostic values of, respectively, tetranectin (TN) and CA-125 measured in serum from patients presenting with relapse of ovarian cancer (OC). METHODS: TN and CA-125 were measured in serum samples from 75 patients with relapse of OC before the start of second-line chemotherapy. The endpoint used was death of OC. The variables were analyzed by univariate life table analysis and multivariate Cox analysis. RESULTS: A significantly shortened survival was found for patients with low serum TN values compared to patients with serum TN levels above one of the cutoff levels. The survivals are illustrated by life tables. No prognostic function was found for CA-125. TN and relapse </=12 months after primary treatment were the only significant independent prognostic variables among the following variables tested in the Cox analyses: primary and second-line treatment, CA-125, age, histology, performance score, tumor localization, and size. CONCLUSION: Serum TN determination may be valuable in the selection of patients with relapse of OC for new treatment strategies in future studies.

Biomarkers, Tumor↗

PubMed2000

Stability of YKL-40 concentration in blood samples.

The stability of YKL-40, a mammalian member of the family of 18 glycosylhydrolases, in blood samples handled under different temperatures and different time intervals before centrifugation was studied in paired serum and plasma samples from 25 healthy premenopausal Danish women. Significant elevations of YKL-40 were found in 8 paired serum samples left on the clot for more than 3 h at room temperature compared to paired serum samples left on the clot for 3 h or less. Significant elevations of YKL-40 were found in 8 paired plasma (EDTA) samples left on the blood cells for more than 8 h at room temperature compared to paired plasma (EDTA) samples left on the blood cells for 8 h or less. No elevations were found in YKL-40 levels in serum samples left on the clot at 4 degrees C for 24 h or in plasma (EDTA) samples left on the blood cells for 72 h before centrifugation. Significantly lower concentrations of YKL-40 were measured in plasma (EDTA) compared with paired serum samples with a serum/plasma ratio of 1.4 in samples left on the clot or on blood cells at 4 degrees C for up to 24 h. Repetitive freezing and thawing had no significant effect on the measured YKL-40 concentrations. In conclusion, we have shown that YKL-40 is very dependent on the handling procedures. All the blood samples must be processed into plasma (EDTA) within 8 h at room temperature or into serum in less than 3 h at room temperature. If this is not possible, the blood samples must be stored at 4 degrees C until processed.

Adipokines↗

PubMed1998

Determination of serum tetranectin: technical and clinical evaluation of three sandwich immunoassays.

The performance of two sandwich-type immunoassays for the determination of the tumour marker tetranectin using monoclonal antibodies Hyb 130-13 and 130-14 as catching layer was compared with the performance of a polyclonal assay. Sensitivities were 0.4-0.6 microg/l, and intra- and inter-assay coefficients of variation were < 10% in all assays. One-hundred-and-ten blood donors were examined, and women had higher concentrations of tetranectin in serum than men when measured with monoclonal assays (P < 0.05). In preoperative serum samples from 43 patients with ovarian cancer, tetranectin concentrations were reduced (P < 0.001), and the mean tetranectin concentration decreased with increasing FIGO stage of the patients (P < 0.05). In sera from patients with ovarian cancer, tetranectin concentrations were lower in the polyclonal assay than in the monoclonal assays. This could, hypothetically, be explained by ligand-binding or other conformational changes in tetranectin, influencing the antigenicity of the molecule.

Adult↗

PubMed1998

Human tetranectin: methodological and clinical studies.

From its discovery in 1986 tetranectin (TN) has been suggested to participate in proteolytic processes through its binding to plasminogen, which enhances the activation of plasminogen to plasmin. Because extracellular proteolysis is an important factor in the ability of malignant cells to infiltrate normal tissues and metastasize, TN was considered to be a potential marker for this proteolysis. We have studied the variations in blood and tissue levels of TN in clinical conditions such as cancer and infection, where increased proteolysis can be expected. Five monoclonal antibodies (MAbs) were produced against human TN, and our study is the first report of stable hybridomas producing MAbs against human TN. All the MAbs reacted with epitopes located within aa-residues 50-181 of the primary sequence. In relative epitope mapping with enzyme immuno assay and isotachophoresis the five MAbs defined two independent epitope groups. Different combinations of MAbs were suitable for enzyme immuno assays and two MAbs could be used for immunohistochemical detection of TN in both fresh frozen and paraffin embedded tissues. The MAbs will facilitate future studies on structure, function, clinical significance and immunolocalization of TN. In primary ovarian cancer neither s/p-TN nor CA 125 were found valuable for diagnosis of localized cancer versus benign tumors. However, s/p-TN combined with CA 125, increased both sensitivity and specificity. S/p-TN should therefore be considered one of the screening markers in conjunction with CA 125, or other comparable markers, in future ovarian cancer screening research studies. Preoperative s-TN was significantly correlated to residual tumor and survival in ovarian cancer patients undergoing second or third look surgery. In conjunction with CA 125 and CASA the predictive value of TN for residual tumor was greatly improved, as the markers were found to supplement each other. If the second look operation had been restricted to patients who had a marker negative test, up to 37% would have avoided surgery. We therefore recommend that these tests are included as potential selection parameters in other studies evaluating second-look surgery. Low p-TN concentration and heavy extracellular staining of TN in the tumors was significantly correlated with a poor prognosis for patients with localized stage I or II or advanced primary ovarian cancer. The prognostic information can be especially valuable for patients with a localized ovarian cancer stage I or II, because about 20% of these patients, believed to be radically operated later present with relapse. We found the p-TN level to be especially useful for patients with localized cancer, indicating that adjuvant chemotherapy may be considered if the p-TN level is low. For patients with advanced primary ovarian cancer and low p-TN the survival was significantly reduced compared to patients with a higher p-TN. The p-TN level was significantly negatively correlated to the extracellular (stromal) staining of TN in the tumors. A heavy stromal TN staining was correlated with a shortened survival and was an independent prognostic factor in the Cox analyses. Patients with advanced primary cancer and a low p-TN, possibly in combination with a heavy stromal staining of TN in the tumors, should tentatively be offered palliative treatment or experimental chemotherapy. Furthermore, patients receiving chemotherapy may be monitored by s/p-TN measurements, as a decrease in TN concentration indicated recurrence 3.6 months prior to clinical diagnosis. A decrease in TN concentration during chemotherapy may therefore indicate change of treatment. Serum TN was a very strong independent prognostic factor of poor treatment response and a shortened survival in patients with metastatic breast cancer. A low pre-chemotherapy s-TN value together with clinical signs of poor treatment response may be an ominous combination, which may suggest change of treatment. For patients with Dukes' stage

Biomarkers, Tumor↗

PubMed1997

Monoclonal antibodies against human tetranectin, epitope characterization and use in immunohistochemistry.

Two IgG2a/kappa- and three IgG1/kappa monoclonal antibodies (MAbs) were produced against human tetranectin (TN): this is the first report of stable hybridomas producing MAbs against TN. All the MAbs reacted with non-conformational epitopes located within amino acid residues 50-181 of the primary sequence. In relative epitope mapping with enzyme immunoassay and isotachophoresis the five MAbs defined two independent epitope groups. One of them is suggested to be immunodominant in rabbits, since MAbs inhibited binding of a polyclonal rabbit antibody. Several combinations of MAbs were suitable for TN-ELISA and two MAbs could be used for immunohistochemical detection of TN in both fresh frozen and paraffin-embedded tissues. The MAbs will facilitate future studies on structure, function, clinical significance and immunolocalization of TN.

Animals↗

PubMed1996

Immunoreactive inhibin concentration in blood tested under variable sampling conditions.

The stability of immunoreactive (i.r.) inhibin in blood samples drawn and handled under different conditions and at different time intervals were studied. Ten serum and plasma samples drawn in 1994 from healthy volunteers were compared to samples collected in 1986 from 10 healthy women admitted for laparoscopic sterilization and analysed 6 years later. All samples were drawn on the twelfth day of the menstrual cycle and handled under identical clinical conditions (22 degrees C). The concentrations in the 1986 samples were similar to the Se-i.r. inhibin levels from 1994. Different clotting temperatures, repetitive freezing and thawing or hemolysis had no effects on the i.r. inhibin values, whereas non-hemolysed samples left at room temperature (22 degrees C) for 3 days were significantly lower, which might be due to a statistical type 2 error. No differences in concentration between serum and plasma i.r. inhibin were demonstrated. In conclusion, i.r. inhibin is a very stable peptide hormone in both serum and plasma if drawn and handled under normal conditions.

Blood Specimen Collection↗

PubMed1996

Use of tetranectin, CA-125 and CASA to predict residual tumor and survival at second- and third-look operations for ovarian cancer.

Tetranectin (TN), CA-125 and CASA were measured in serum prior to 63 second-look and 5 third-look operations for ovarian cancer. Patients with residual tumor had significantly lower levels of TN and higher levels of CASA and CA-125 compared with tumor-free patients. The predictive values PVPos = 100% and PVNeg = 50.9% were found for TN at 9.3 mg/l. For CASA, a predictive value PVPos = 100% was found at 10 U/ml with a corresponding PVNeg = 52.7%. At the cut-off 35 U/ml for CA-125, the PVPos was 100% and the PVNeg = 53.6%. By combining the markers, PVNeg increased to 61.7% with a PVPos on 100%. Significantly differences in survival were found by lifetable analysis between patients tested as positive and negative respectively for any of the markers. Using multivariate Cox analyses, it was found that every marker had an independent prognostic function for survival.

Adult↗

PubMed1995

Alpha-fetoprotein and the acute phase response. A study using acute pelvic inflammatory disease as a model system.

Alpha-fetoprotein (AFP) is used as a tumor marker for hepatomas and germ cell tumors. In healthy non-pregnant adults the serum concentration (S-AFP) is very low and we examined whether it was affected when the acute phase response was activated, using patients with acute pelvic inflammatory disease (PID) as a model system. In 70 PID patients the median S-AFP was 1.2 kIU/l (range: 0.5-5.9 kIU/l), within the normal range. S-AFP did not correlate with the clinical grade of disease nor with the serum concentrations of acute phase reactants and albumin. Thus, S-AFP is not significantly affected by activation of the acute phase response and presence of infection should not per se interfere with the use of S-AFP as a tumor marker. However, a negative correlation was found with the serum concentration of alpha-2-macroglobulin (P = 0.05), but whether this has any biological significance remains to be clarified.

Acute-Phase Proteins↗

PubMed1995

The role of serum tetranectin, CA 125, and a combined index as tumor markers in women with pelvic tumors.

Serum tetranectin (Se-TN) and CA-125 were measured in 315 patients with a pelvic tumor and 458 healthy females. At a false-positive rate of 0.7% the sensitivity for ovarian cancer stage 1 and 2 was 33% for Se-TN and 76% for both CA 125 and an index based on Se-TN and CA 125 (Index 1). At a false-positive rate of 0.4% the sensitivity was 29% for Se-TN, 62% for CA 125 (35 U/ml), and 76% for Index 1. A negative correlation was found between the Se-TN level and the stage of cancer. The sensitivity for benign tumors was 6% for Se-TN, 17% for CA 125, and 21% for Index 1 at a false-positive rate of 0.4%. In the present study the sensitivity and specificity levels of Se-TN were not sufficiently high to warrant the use of Se-TN as an individual marker for ovarian cancer. The sensitivity rose with the index-based Se-TN and CA 125 without causing a concomitant increase in the rate of false-positive results. None of the markers rose to levels that would allow their use in clinical diagnosis to discriminate between localized cancer and benign tumors.

Adolescent↗

PubMed1995

Ovarian carcinoma serum markers and ovarian steroid activity--is there a link in ovarian cancer? A correlation of inhibin, tetranectin and CA-125 to ovarian activity and the gonadotropin levels.

In a previous study, we have demonstrated that inhibin-production may be associated with improved survival and, also, that tetranectin (TN) is a valuable prognostic marker in ovarian epithelial cancer. We investigated the possible correlation between inhibin, tetranectin, CA-125, ovarian steroid activity and the gonadotropin levels. Preoperative serum levels of the tumor markers inhibin, tetranectin (TN) and CA-125 were measured and related to ovarian steroid function and the pituitary-gonadal axis (gonadotropin levels) in 28 postmenopausal ovarian cancer patients. The following median levels and 95% confidence limits were demonstrated for the tumor markers: Inhibin 0.4 U/l (0.2-0.9), TN 8.9 mg/l (6.8-9.2), CA-125 160 kU/l (75-687). A significant inverse correlation was demonstrated between inhibin and the gonadotropins. The Spearman correlation coefficients showed a highly significant correlation of inhibin with the examined ovarian steroid hormones except DHEAS which also has a suprarenal component. This indicates a synthesis of inhibin and the steroid hormones from the same cell compartment as known from the normal ovary and an apparently intact negative feed back mechanism. Inhibin may be produced in the normal ovary as a defense mechanism against an elevated gonadotropin level and inhibin acts by lowering the gonadotropins or by altering their biological activity. Elevated values of the tumor markers TN and CA-125 due to gonadotropin stimulation could not be demonstrated but a significant inverse correlation between TN and CA-125 was confirmed.

Adenocarcinoma↗

PubMed1995

Plasma tetranectin and colorectal cancer.

The prognostic significance of plasma tetranectin (PL-TN) in colorectal cancer was retrospectively examined in 504 patients (80 Dukes' A, 174 Dukes' B, 98 Dukes' C and 152 Dukes' D). Follow-up time was 7-12 years. No significant prognostic variable was found for Dukes' A patients by Cox multivariate analysis. In stage B, PL-TN was the second strongest prognostic variable [relative hazard (RH) = 3.3 for patients with PL-TN < or = 7.5 mg/l]. The other prognostic variables were perineural invasion (RH = 3.7), tumour distance < or = 10 cm from the anal verge (RH = 3.0), postoperative radiotherapy (RH = 2.9) and a high carcinoembryonic antigen (CEA) score (RH = 1.8). In Dukes' C, only CEA score and gender were of prognostic significance. For Dukes' D, PL-TN was the only prognostic variable (RH = 1.7). Testing all patients in one multivariate analysis, Dukes' staging was the strongest and PL-TN the second strongest prognostic variable. The shortened survival for patients with low PL-TN levels is illustrated with lifetables.

Aged↗

PubMed1995

Serum tetranectin in patients with acute pelvic inflammatory disease (PID). Correlation to clinical and laboratory findings.

AIM OF STUDY: To clarify the impact of the presence of pelvic inflammatory disease (PID) and activation of the acute phase response on the serum level of tetranectin (Se-TN), a potential new tumor marker for ovarian cancer. MATERIALS AND METHODS: The study group consisted of 70 patients with a laparoscopically verified PID and 47 healthy female controls. RESULTS: Lower Se-TN levels were found for the PID group compared to the control group (p < 0.0001). It was not possible to relate the decreases in Se-TN levels to any distinct bacterial strain. Neither was it possible to find any correlation between Se-TN and severity of PID (p = 0.5). A significant positive correlation was found between Se-TN and ALB (p < 0.001). A just significant negative correlation was found between Se-TN and C-reactive protein (CRP) (p = 0.04), while no correlation was found with any of the other acute phase reactants. Highly significant correlations were found between all the acute phase reactants and grade of PID. CONCLUSIONS: A slight, but significant reduction in Se-TN was found in PID patients. The decrease was minor compared to the reported findings of very low Se-TN levels for ovarian cancer patients. However, the finding is important in the assessment of TN used as a potential screening marker for ovarian cancer, or as a diagnostic tool for pelvic tumors. Furthermore, Se-TN does not seem to behave as a negative acute phase reactant.

Acute-Phase Proteins↗