Clinical Significance of Measuring Prostate-Specific Antigen

The incidence of prostate-specific antigen (PSA) monitoring has increased in recent years. However, interpretation of the results is often ambiguous and leads to uncertainty for both the patient and the treating physician. Advantages and disadvantages of measuring PSA and possibilities for improved interpretation using the variable PSA quotient are given. After reading this article, readers should be able to better interpret PSA values and assess the risk of prostate carcinoma using PSA quotient. In addition, errors associated with PSA and PSA quotient measurement are compared and discussed. Chemistry exam 20907 questions and corresponding answer form are located after this CE Update on pag…

The enemy in you: the interdependency of the localisation and antigenicity of proteins

The subcellular localisation of protein components should be important for their antigenicity. This assumption is derived from the concept of MHC restriction, where CD4 and CD8 T lymphocytes can only interact with MHC II and MHC I surface receptors, respectively. If this mechanism applies, however, then intracellular components should have immunogenic effects mediated by MHC II and CD4 T lymphocytes as soon as they enter the extracellular space. Conversely, extracellular components should generate an immune response that is mediated by MHC I and CD8 lymphocytes when they breach the intracellular space and when they exceed a critical concentration. In this study, these hypotheses were invest…

High-Sensitivity Procalcitonin (hs-PCT): A Marker for Identification of Arteriosclerosis and Myocardial Infarction?

Background: Procalcitonin (PCT) is a protein hormone induced by bacterial inflammation that serves as a marker of sepsis. C-reactive protein (CRP) is also known to be a marker of inflammation and, in low concentrations, a prognostic marker for latent or early arteriosclerosis. Arteriosclerosis is considered as an inflammatory process that begins in the wall of an artery. In addition to CRP, the concentration of other markers of inflammation increases in the presence of arteriosclerosis. Methods: To determine if PCT is among these markers, the serum concentration of PCT was quantified in blood samples from healthy individuals (n = 410) and at admission in 774 patients, 92 with peripheral art…

Comment on the Letter to the Editor by Professor Reiber

Author’s Response to Professor Reiber’s second letter concerning our article: High sensitivity of free lambda and free kappa light chains for the detection of intrathecal immunoglobulin synthesis in cerebrospinal fluid

Rapid and reliable genotyping procedure for detection of alleles with mutations, deletion, or/and duplication of the CYP2D6 gene

Abstract Background Polymorphisms of cytochrome P450 2D6 (CYP2D6) have a significant effect on the pharmacokinetics of most tricyclic antidepressants. More than 150 alleles lead to four distinct phenotypes of drug metabolism. The phenotypes are described as ultrarapid, extensive, intermediate, and poor metabolizers. Therapeutic plasma levels of CYP2D6 substrates may be difficult to achieve. Here we describe a rapid and reliable procedure for CYP2D6*4, *3, *6, and *9 genotyping. Design and methods Serum concentrations of venlafaxine and its pharmacologically active metabolite, O-desmethylvenlafaxine, were measured in patients treated with the antidepressant venlafaxine, a substrate of CYP2D6…

Experimental confirmation of the 'protein traffic hypothesis' by routine diagnostic tests

The 'protein traffic hypothesis' suggests that the inflammation associated with autoimmune disease, trauma and disturbances of blood circulation is the result of misguided protein trafficking. The hypothesis divides the antigen spectrum into an intracellular component and an extracellular component. While the intracellular component is recognised by MHC class-I molecules and is presented to CD8 T-lymphocytes, the extracellular component is recognised by MHC class-II molecules and is presented to CD4 T-lymphocytes. To test this hypothesis, CD4 and CD8 T-cell counts of 271 HIV-negative patients of the University Hospital, Mainz, Germany were examined retrospectively. The results corroborate t…

Error calculation for the PSA quotient.

Abstract Objective Prostate specific antigen (PSA) assays have significant measurement errors, but the error associated with the PSA quotient (free to total PSA) often remains unknown. Methods We used both Gaussian error calculation and measurement of imprecision to investigate the level of error associated with the PSA quotient. Results Surprisingly, we found that the error of the PSA quotient at low levels is markedly smaller than that of the total PSA value. Conclusions The PSA quotient should be calculated and considered as a clinically relevant value.

High sensitivity of free lambda and free kappa light chains for detection of intrathecal immunoglobulin synthesis in cerebrospinal fluid.

Background –  So far, an inflammation of the central nervous system (CNS) is diagnosed by immunoglobulin measurement in cerebrospinal fluid (CSF) and serum as well as by determination of the oligoclonal bands. With the free kappa and lambda light chains, new markers to diagnose intrathecal synthesis are available. Methods –  In addition to routine diagnostic tests and the assessment of standard parameters, free immunoglobulin light chains were measured in the CSF of patients with neurological disorders. Results –  A significant agreement was found between an increase in free kappa light chain CSF serum quotients and results of the currently widely applied method of oligoclonal band measurem…

Sequence Variability and Sequence Evolution: An Explanation of Molecular Polymorphisms and Why Many Molecular Structures Can Be Preserved Although They Are Not Predominant

The existence of many processes that regulate RNA expression poses a challenge to the idea that the cell is the culmination of a highly efficient interplay of individual proteins, each with specific, highly specialized functions. It will be demonstrated here the extent to which the cell may undergo evolutionary processes that also occur in the macrocosmos, specifically with reference to the rules of mutation and preservation. These molecular evolutionary processes could facilitate a better understanding of the development of molecular structures and the functioning of the cell and could give an explanation of the molecular polymorphisms and also explain why many molecular structures can be …

Sexual selection and intelligence: Does sexual reproduction drive the evolution of intelligence?

Abstract The basal hypothesis discussed here is the idea that brain architecture could be plastic on a very basal, genetic level due to sexual recombination and reassortment of alleles of genes related to brain development, e.g., neuronal cell adhesion molecules (NCAMs) and others. The role of sexual reassortment leads the study of brain development, species behavior and intelligence to a new version of the so-called “Red Queen Hypothesis”: using the mechanism described here, a kind of runaway selection mechanism seems to arise. Even if NCAMs are almost constant within an individual, they seem to act very differently at the population level and so the role of reassorting polymorphic NCAM- (…

Dependence of T-lymphocyte activation on the extent of cellular damage

Mechanically damaged cells release intracellular substances, resulting in the activation of CD4- and CD8-positive T-lymphocytes. The goal of this investigation was to quantify and compare fractions of activated CD4- and CD8-positive T-lymphocytes, based on the quantity of damaged cells in a given blood sample. Blood samples were mechanically stressed by vortexing intensely. Subsequently, different quantities of distressed blood samples were mixed with samples of fresh, whole blood. Afterwards, the extent of CD4- and CD8-positive T-cell activation was examined in the mixture by flow cytometry. Sine-like curves of T-cell activation were observed for both CD4- (T-helper mediated) and CD8- (cyt…

Concentration-dependent T cell activation by different types of proteins

We investigated the concentration-dependent stimulation of T cells by different human proteins. Quantitative changes in the extent of activation, as well as qualitative changes within the type of activation, were measured. At low, physiological concentrations of extracellular human proteins (0.2 µg/ml), CD4 and CD8 T lymphocytes were suppressed. In contrast, at high protein concentrations (2 mg/ml), CD4 T cells were suppressed, but we also observed a concurrent increase in the level of CD8 T cell activation. Our results are consistent with the phenomenon of cross-presentation, whereby the addition of intracellular proteins leads to the activation of both CD4 and CD8 T cells. Further additio…

Measurement of T Cell Activation After 16‐hr In Vitro Stimulation with Concanavalin A

A flow cytometry assay that can be used to directly determine the proportion of activated T lymphocytes in human whole blood samples after stimulation with concanavalin A is presented here. Human whole blood is incubated with fluorescently labeled antibodies (against CD3, CD4, CD8, and CD69), erythrocytes are then lysed, and the samples are analyzed using a flow cytometer. The assay presented is able to differentiate between CD4+ and CD8+ T lymphocytes. Thus, it is possible to quantify both lymphocyte populations in parallel, as well as the respective proportions of activated T lymphocytes, all from one sample. An additional advantage of this assay is that it was developed to assay whole bl…

CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine.

SUMMARY Background: Venlafaxine (V) is a mixed serotoninand noradrenaline reuptake inhibitor used as afirst-line treatment of depressive disorders. It ismetabolized primarily by the highly polymorphiccytochrome P450 (CYP) enzyme CYP2D6 to yielda pharmacologically active metabolite, O-des-methylvenlafaxine (ODV), and to a lesser extentby CYP3A4, to yield N-desmethylvenlafaxine(NDV).Objectives: The aim of this study was to assesswhether the O-demethylation phenotype of V hasan impact on the pharmacokinetics and clinicaloutcome.Method: In 100 patients treated with V, serumconcentrations of V, ODV and NDV and theratios of concentrations ODV/V as a measure ofO-demethylation were determined. Indiv…