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J Leinonen

Publications and source records attributed to J Leinonen.

At least 19 recordsLinked to original sources
PubMed2005

1H MRS studies in the Finnish boron neutron capture therapy project: detection of 10B-carrier, L-p-boronophenylalanine-fructose.

This article summarizes the current status of 1H MRS in detecting and quantifying a boron neutron capture therapy (BNCT) boron carrier, L-p-boronophenylalanine-fructose (BPA-F) in vivo in the Finnish BNCT project. The applicability of 1H MRS to detect BPA-F is evaluated and discussed in a typical situation with a blood containing resection cavity within the gross tumour volume (GTV). 1H MRS is not an ideal method to study BPA concentration in GTV with blood in recent resection cavity. For an optimal identification of BPA signals in the in vivo 1H MR spectrum, both pre- and post-infusion 1H MRS should be performed. The post-infusion spectroscopy studies should be scheduled either prior to or, less optimally, immediately after the BNCT. The pre-BNCT MRS is necessary in order to utilise the MRS results in the actual dose planning.

Adult↗
PubMed2001

The identification of secreted carbonic anhydrase VI as a constitutive glycoprotein of human and rat milk.

In addition to essential nutrients, human milk contains several classes of bioactive factors such as enzymes, hormones, and growth factors, many of which are implicated in infantile growth and development. Secretory carbonic anhydrase isoenzyme VI (CA VI) has been identified earlier as an essential component of mammalian saliva, and we demonstrate here by using biochemical and immunohistochemical techniques that it is also an elementary component of milk. The 42-kDa glycopolypeptide purified from human milk in CA inhibitor affinity chromatography shared 100% homology with salivary CA VI in the protein sequence analysis (40% coverage), and its digestion with PNGase F resulted in a polypeptide backbone similar in size to salivary CA VI. Quantification of CA VI in milk by using a time-resolved immunofluorometric assay revealed an approximately eight-times-higher concentration in human colostrum than in mature milk, the latter corresponding to the levels previously detected in human saliva. The high concentration in the colostrum, in particular its functional and structural stability in an acidic milieu, and its growth-supporting role in the taste buds suggest that milk CA VI is an essential factor in normal growth and development of the infant alimentary tract.

Animals↗
PubMed2001

Validity of the prostate specific antigen test for prostate cancer screening: followup study with a bank of 21,000 sera in Finland.

PURPOSE: We investigate the validity of prostate specific antigen (PSA) as a screening test for prostate cancer. MATERIALS AND METHODS: A registry of serum samples drawn from 1968 to 1976 from 21,387 men was linked to the Finnish Cancer Registry. During followup from 1968 to 1991, 104 prostate cancers were identified. A matched case control design with incidence density sampling and nested in the serum sample bank was applied, and PSA was assessed. RESULTS: The estimated sensitivity of the test was 44% and specificity 94% at a cutoff of 4.0 microg./l. in the total material. The sensitivity had improved to 86% in patients diagnosed in 5 years after the sample drawing. The test had a better sensitivity (93%) and specificity (96%) in men younger than 65 years at the time of the sample drawing compared to those older. The sensitivity further improved to 100% with a cutoff of 2.5 microg./l. CONCLUSIONS: PSA is a valid screening test for prostate cancer, which compares favorably with mammography for breast cancer. However, until an effect on mortality has been shown, routine screening cannot be recommended.

Adolescent↗
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

Secretion of carbonic anhydrase isoenzyme VI (CA VI) from human and rat lingual serous von Ebner's glands.

Salivary carbonic anhydrase VI (CA VI) appears to contribute to taste function by protecting taste receptor cells (TRCs) from apoptosis. The serous von Ebner's glands locating in the posterior tongue deliver their saliva into the bottom of the trenches surrounding the TRC-rich circumvallate and foliate papillae. Because these glands deliver their saliva directly into the immediate vicinity of TRCs, we investigated whether CA VI is secreted by the von Ebner's glands, using immunochemical techniques. The immunohistochemical results showed that CA VI is present in the serous acinar cells, ductal cells, and ductal content of von Ebner's glands and in the demilune and ductal cells plus ductal content of rat lingual mucous glands. More importantly, CA VI was also detected in taste buds and in the taste pores. Western blotting of saliva collected from the orifices of human von Ebner's glands and CAs purified from rat von Ebner's glands confirmed that CA VI is expressed in these glands and secreted to the bottom of the trenches surrounding the circumvallate and foliate papillae. These findings are consistent with the hypothesis that locally secreted CA VI is implicated in the paracrine modulation of taste function and TRC apoptosis. (J Histochem Cytochem 49:657-662, 2001)

Animals↗
PubMed2000

Determination of prostate-specific antigen complexed to alpha(2)-macroglobulin in serum increases the specificity of free to total PSA for prostate cancer.

OBJECTIVES: To determine whether prostate-specific antigen (PSA) complexed to alpha(2)-macroglobulin (A2M) increases the specificity of free PSA (fPSA) and total PSA (tPSA) for the diagnosis of prostate cancer (PCa). METHODS: In a series of 73 patients with PCa and 58 with benign prostatic hyperplasia (BPH), fPSA, tPSA, and PSA complexed with A2M (PSA-A2M) in serum were determined by specific immunoassays. The assay for PSA-A2M was based on the immunoadsorption of immunoreactive PSA in serum and the measurement of the PSA immunoreactivity released by denaturation of PSA-A2M at pH 11.4. RESULTS: The median proportion of PSA-A2M [ %PSA-A2M=PSA-A2M/(tPSA+PSA-A2M)] and that of fPSA ( %fPSA=fPSA/tPSA) were significantly lower in patients with PCa (8.2% and 12.4%, respectively) than in patients with BPH (11.6% and 22.5%, P = 0.0014 and P <0.0001, respectively). The median sum of %PSA-A2M and %fPSA was 22.4% in PCa and 38.2% in BPH (P <0.0001). When the sum of %PSA-A2M and %fPSA was used as a diagnostic test for PCa, 57% of patients with "falsely" elevated PSA concentrations (4 to 10 ng/mL) caused by BPH could be correctly identified without missing patients with PCa compared with 18% of the patients with BPH but not PCa using %fPSA alone. CONCLUSIONS: Measurement of the sum of %PSA-A2M and %fPSA in serum significantly improves the cancer specificity of the PSA test compared with the use of tPSA and %fPSA.

Aged↗
PubMed2000

Identification of novel prostate-specific antigen-binding peptides modulating its enzyme activity.

Prostate-specific antigen (PSA) is a serine protease with highly prostate-specific expression. Measurement of PSA in serum is widely used for diagnosis and monitoring of prostate cancer. PSA dissolves the seminal gel forming after ejaculation. It has been suggested to mediate invasion and metastasis of prostate cancer but also to exert antiangiogenic activity. We have identified peptides specific for PSA by screening cyclic phage display peptide libraries. PSA-binding peptides were isolated from four different libraries and produced as a fusion protein with glutathione S-transferase (GST). The phage and fusion proteins were shown to bind to PSA specifically as indicated by lack of binding to other serine proteinases. A peptide with four cysteines showed the highest affinity for PSA. Zn2+, an inhibitor of PSA activity, increased the affinity of the peptides to PSA. The binding specificity was characterized by cross-inhibition using monoclonal anti-PSA antibodies of known epitope specificities. The peptides bound to the same region as mAbs specific for free PSA indicating that they bind close to the active site of the enzyme. The peptides enhanced the enzyme activity of PSA against a chromogenic substrate. These results show that peptides binding to PSA and modulating its enzyme activity can be developed by phage display technique. The peptides have the potential to be used for identification of PSA variants and for imaging and targeting of prostatic tumors.

Amino Acid Sequence↗
PubMed2000

Use of the complex between prostate specific antigen and alpha 1-protease inhibitor for screening prostate cancer.

PURPOSE: We assess whether the complex between prostate specific antigen (PSA) and alpha1-protease inhibitor in serum can be used to reduce further the number of false-positive PSA screen results independent of total and free PSA. MATERIALS AND METHODS: Sera from 304 consecutive screen positive subjects, including 78 with and 226 without prostate cancer, and serum PSA of 4 to 10 microg./l. or higher in the Finnish, randomized, population based prostate cancer screening trial were analyzed for PSA-alpha-protease inhibitor, and total and free PSA. Main outcome measures were specificity, sensitivity and area under receiver operating characteristics curve for proportions of free PSA and PSA-alpha 1-protease inhibitor, and for a combination of these among screen positive cases. RESULTS: The proportion of serum PSA-alpha 1-protease inhibitor of total PSA was lower in cancer cases than in controls (0.9% versus 1.6%, p <0.001). Logistic regression analysis of total PSA, free PSA and PSA-alpha 1-protease inhibitor showed that PSA-alpha 1-protease inhibitor in serum was an independent variable for discrimination between subjects with and without prostate cancer (p = 0.006) in the PSA range of 4 to 10 microg./l. The proportion of PSA-alpha 1-protease inhibitor alone improved specificity less than the proportion of free PSA but when these were combined by logistic regression they performed better than the proportion of free PSA alone at sensitivities of 85% to 95% (p <0.001). CONCLUSIONS: Serum PSA-alpha 1-protease inhibitor improves the specificity of total and free PSA in a screening population with total PSA 4 to 10 microg./l.

Aged↗
PubMed2000

Characterization and determination of the complex between prostate-specific antigen and alpha 1-protease inhibitor in benign and malignant prostatic diseases.

Prostate-specific antigen (PSA) is a tissue-specific serine protease which forms complexes with protease inhibitors such as alpha 1-antichymotrypsin and alpha 2-macroglobulin. We have studied the interaction between PSA and alpha 1-protease inhibitor (API) in vitro and found that 15% of the added PSA binds to API while the majority of API is cleaved between Met358 and Ser359 when PSA is incubated with a 5-fold excess of API at 37 degrees C for 7 days. The complex between PSA and API (PSA-API) formed in vitro displays the same chromatographic behavior, molecular size and immunoreactivity as endogenous PSA-API occurring in serum, indicating that they are identical. PSA-API can be detected in serum by a time-resolved immunofluorometric assay (IFMA), in which a monoclonal antibody to PSA is used as a catcher and a polyclonal antibody to API labeled with a Eu-chelate is used as a tracer. Purified PSA-API formed in vitro is used as a calibrator. PSA-API in serum represents 1.0-7.9% (median 2.4%) of total PSA (tPSA) in prostate cancer (PCa, n = 82) and 1.3-12.2% (median 3.6%, p < 0.01) in patients with benign prostatic hyperplasia (BPH, n = 66). The IFMA for PSA-API in serum is hampered by a variable background, which is caused by non-specific adsorption of the huge excess of API in serum to the solid phase. The background can be determined by an assay using the same tracer as in the IFMA for PSA-API but PSA-unrelated antibody on the solid phase. The background signal is subtracted from the PSA-API signal. The clinical utility of PSA-API in serum has been evaluated in PSA-positive subjects from the Finnish PCa screening trial. After subtraction of the background, the proportion of PSA-API in relation to tPSA is lower in PCa than in controls, 0.9% vs. 1.6%, respectively (p < 0.001). Logistic regression analysis showed that the concentration of PSA-API was independent of the proportion of free PSA as a diagnostic variable among subjects with a tPSA of 4-10 micrograms/l (p = 0.009). The probability of PCa calculated by logistic regression using the concentration of PSA-API and the proportion of free PSA in serum significantly improved cancer specificity at high sensitivity levels (85-95%) as compared to the proportion of free PSA alone.

Humans↗
PubMed2000

Development of novel peptide ligands modulating the enzyme activity of prostate-specific antigen.

Prostate-specific antigen (PSA) is a serine proteinase produced mainly by epithelial cells of the prostate. Measurement of PSA in serum is widely used for diagnosis and monitoring of prostate cancer. The major problem of the PSA determination in early diagnosis is the high false positive rate due to benign prostatic hyperplasia, but the clinical accuracy can be improved by determining the proportions of various molecular forms of PSA. The main biological function of PSA is liquefaction of the seminal gel formed after ejaculation, but PSA has also been suggested to regulate invasiveness and metastatic potential of prostatic tumors. Thus, agents binding to and affecting the function of PSA have the potential to be used for diagnosis and therapy of prostate cancer. We have developed peptides specific for PSA by using cyclic phage display peptide libraries. After deducing the amino acid sequence of the peptides by sequencing the relevant part of phage genome, the peptides were expressed as glutathione-S-transferase (GST) fusion proteins or produced by chemical synthesis. The peptides were shown to bind to PSA specifically as indicated by lack of binding to other related serine proteinases. The binding of the peptides with PSA was strongly inhibited by monoclonal antibodies specific for free PSA and they did not bind to PSA-inhibitor complexes indicating that they bind close to the active site of the enzyme. Most of the peptides enhanced the enzyme activity of PSA against a chromogenic substrate. The affinity of the peptides could be increased by including Zn2+ in the reaction mixture. These results show that peptides that bind to PSA and modulate its enzyme activity can be developed by phage display techniques. These peptides have the potential to be used for targeting of prostatic tumors and diagnostics of prostate cancer.

Humans↗
PubMed1999

Salivary carbonic anhydrase isoenzyme VI.

The carbonic anhydrases (CAs) participate in the maintenance of pH homeostasis in various tissues and biological fluids of the human body by catalysing the reversible reaction CO2 + H2O HCO3- + H+ (Davenport & Fisher, 1938; Davenport, 1939; Maren, 1967). Carbonic anhydrase isoenzyme VI (CA VI) is the only secretory isoenzyme of the mammalian CA gene family. It is exclusively expressed in the serous acinar cells of the parotid and submandibular glands, from where it is secreted into the saliva. In this review, we will discuss recent advances in research focused on the physiological role of salivary CA VI in the oral cavity and upper alimentary canal.

Carbonic Anhydrases↗
PubMed1999

Prostate-specific antigen.

Prostate specific antigen (PSA) is serine protease produced at high concentrations by normal and malignant prostatic epithelium. It is mainly secreted into seminal fluid, where it digests the gel forming after ejaculation. Only minor amounts of PSA leak out into circulation from the normal prostate, but the release of PSA is increased in prostatic disease. Thus PSA is a sensitive serum marker for prostate cancer but its specificity is limited by a high frequency of falsely elevated values in men with benign prostatic hyperplasia (BPH). Approximately two-thirds of all elevated values (>4 microg/l) in men over 50 years of age are due to BPH. In serum, most of the PSA immunoreactivity consists of a complex between PSA and alpha1-antichymotrypsin (PSA-ACT) whereas approximately 5-40% are free. The proportion of PSA-ACT is larger and the free fraction is smaller in prostate cancer than in benign prostatic hyperplasia (BPH). Determination of the proportion of free PSA has become widely used to improve the cancer specificity of PSA especially in men with PSA values in the 'grey zone' (4-10 microg/l). PSA also occurs in complexes with other protease inhibitors and determination of these and other markers may further improve the diagnostic accuracy for prostate cancer. Interpretation of the results for many different markers is complicated, but this can be simplified by using statistical methods. The diagnostic accuracy can be further improved by using logistic regression or neural networks to estimate the combined impact of marker results and other findings like digital rectal examination (DRE), transrectal ultrasound (TRUS) and heredity.

Humans↗
PubMed1999

The decrease of visual acuity in cataract patients waiting for surgery.

PURPOSE: To investigate the rapidity of vision loss in eyes waiting for cataract surgery and to estimate what proportion of life expectancy the extended wait for surgery comprised. METHODS: The visual acuities at the time of referral and on the day before surgery were compared in 124 patients operated on for cataract in the Vaasa Central Hospital, Finland. The expected survival of the patients after surgery was calculated individually using the Finnish life statistics. RESULTS: During the waiting time of 13 months on the average, the visual acuity in the study eye decreased from 0.68 logMAR (0.2 in decimal values) to 0.96 logMAR (0.1). The average decrease in vision was 0.27 logMAR per year varying from none to 2.07 logMAR units. 30% of the eyes experienced worsening of vision by 60% or more while 48% had no or minimal worsening (<0.2 logMAR). The rapidity of change in visual acuity was somewhat less in older patients (75 years or older), but the difference was not statistically significant. The percentage of persons with visual acuity of 0.5 or better in the better eye decreased from 66% to 41% and those with low vision (<0.3 in the better eye) increased from 8% to 21%. The mean waiting time in relation to the expected survival for all patients was 13% varying from less than 5% in 10 patients to more than 25% in 8 patients. CONCLUSION: Progression of vision loss in eyes waiting for cataract surgery varies significantly. For many patients the extended delay caused remarkable disability for a considerable part of their remaining lifetime.

Aged↗
PubMed1999

Summary report of the TD-3 workshop: characterization of 83 antibodies against prostate-specific antigen.

Twelve research groups participated in the ISOBM TD-3 Workshop in which the reactivity and specificity of 83 antibodies against prostate-specific antigen (PSA) were investigated. Using a variety of techniques including cross-inhibition assays, Western blotting, BIAcore, immunoradiometric assays and immunohistochemistry, the antibodies were categorized into six major groups which formed the basis for mapping onto two- and three-dimensional (2-D and 3-D) models of PSA. The overall findings of the TD-3 Workshop are summarized in this report. In agreement with all participating groups, three main antigenic domains were identified: free PSA-specific epitopes located in or close to amino acids 86-91; discontinuous epitopes specific for PSA without human kallikrein (hK2) cross-reactivity located at or close to amino acids 158-163; and continuous or linear epitopes shared between PSA and hK2 located close to amino acids 3-11. In addition, several minor and partly overlapping domains were also identified. Clearly, the characterization of antibodies from this workshop and the location of their epitopes on the 3-D model of PSA illustrate the importance of selecting appropriate antibody pairs for use in immunoassays. It is hoped that these findings and the epitope nomenclature described in this TD-3 Workshop are used as a standard for future evaluation of anti-PSA antibodies.

Antibodies, Monoclonal↗
PubMed1999

Reactivity of 77 antibodies to prostate-specific antigen with isoenzymes and complexes of prostate-specific antigen.

Seventy-seven antibodies submitted to the ISOBM TD-3 PSA Workshop (TD-3.1 and TD-3.2) were characterized by measuring their reactivity with isoenzymes of free prostate-specific antigen (PSA), PSA complexed to alpha1-antichymotrypsin (PSA-ACT) and alpha1-proteinase inhibitor (PSA-API). Antibodies were classified into 15 distinct groups according to their reaction profiles with the various isoenzymes. Some antibodies recognizing both free and complexed PSA were inaccurate in measuring total PSA. Eight of the 9 free PSA-specific antibodies cross-reacted more with PSA-API than with PSA-ACT, while 1 antibody reacted less with PSA-API than PSA-ACT. From the panel of antibodies 39 reacted with both free and complexed PSA and were classified as total PSA antibodies.

Antibodies, Monoclonal↗
PubMed1999

Reactivity of anti-PSA monoclonal antibodies with recombinant human kallikrein-2.

Seventy-nine monoclonal antibodies submitted to the ISOBM TD-3 PSA Workshop were tested for their reactivity with recombinant human kallikrein-2 (rhK2). A sandwich immunofluorometric assay using polyclonal anti-prostate-specific antigen (PSA) antiserum-coated plates was used to capture rhK2 and subsequently the test antibody. The response of each test antibody was compared with 3 reference antibodies (H50, H117 and 5E4) known to react with hK2. Nine antibodies from the workshop panel failed to react with purified PSA and rhK2 in this assay and were subsequently excluded. From the remaining panel of antibodies, 11/70 showed strong reactivity with rhK2, 9/70 showed weak reactivity with rhK2, while 50/70 antibodies did not react with rhK2 in this assay format. All antibodies binding to rhK2 recognized both free and complexed PSA.

Antibodies, Monoclonal↗