Serum prostate-specific antigen (PSA) is composed of the PSA precursor protein (proPSA) in the absence of the leader peptide induced by human kallikrein 2 (hK2). There are many forms of PSA in the blood, including free PSA and bound PSA. Serum proPSA, as a free PSA, has many isoforms, among which, [-2]proPSA (p2PSA) cannot be activated by hK2 and therefore exists stably in the blood. Serum p2PSA is a homologous isomer of PSA. Serum prostate health index and % p2PSA, as the derivative indexes of p2PSA and molecular markers associated with the development and progression of prostate cancer, can reduce serum PSA test-induced excessive diagnosis and treatment of the malignancy and improve the accuracy of its prediction. This review summarizes recent progress in the studies of serum p2PSA and its derivative indexes in prostate cancer.
Humans ; Male ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; blood ; immunology ; Protein Isoforms ; blood

Adiponectin ; blood ; metabolism ; Cytokines ; blood ; Female ; Humans ; Male ; Oxidation-Reduction ; Protein Isoforms ; blood ; metabolism ; Pulmonary Disease, Chronic Obstructive ; blood

Prostate-specific antigen (PSA) is recognized as an organ-specific marker with low specificity and sensitivity in discriminating prostate cancer (PCa) from other benign conditions, such as prostatic hyperplasia or chronic prostatitis. Thus, in the case of clinical suspicion, a PCa diagnosis cannot be made without a prostate biopsy. [-2]proPSA (p2PSA), a precursor of PSA, has been investigated as a new marker to accurately detect PCa. The aim of this systematic review was to discuss the available literature regarding the clinical validity and utility of p2PSA and its derivatives, p2PSA/fPSA (%p2PSA) and the Prostate Health Index (PHI). A systematic search of the PubMed and Scopus electronic databases was performed in accordance with the PRISMA statement (http://www.prisma-statement.org), considering the time period from January 1990 to January 2014 and using the following search terms: proprostate specific antigen, proenzyme PSA, proPSA, [-2]proPSA, p2PSA, Prostate Health Index, and PHI. To date, 115 studies have been published, but only 35 were considered for the qualitative analysis. These studies suggested that p2PSA is the most cancer-specific form of PSA, being preferentially expressed in PCa tissue and being significantly elevated in the serum of men with PCa. It is now evident that p2PSA, %p2PSA, and PHI measurements improve the specificity of the available tests (PSA and derivatives) in detecting PCa. Moreover, increasing PHI values seem to correlate with more aggressive disease. Some studies have compared p2PSA and its derivatives with other new biomarkers and found p2PSA to be significantly more accurate. Indeed, the implementation of these tests in clinical practice has the potential to significantly increase the physician's ability to detect PCa and avoid unnecessary biopsies, while also having an effective impact on costs. Further studies in large, multicenter, prospective trials are required to confirm these encouraging results on the clinical utility of these new biomarkers.
Humans ; Male ; Prostate-Specific Antigen/*blood ; Prostatectomy ; Prostatic Neoplasms/*diagnosis/pathology/surgery ; Protein Isoforms/blood ; Protein Precursors/*blood ; Sensitivity and Specificity ; Severity of Illness Index ; Tumor Markers, Biological/blood

The pathogenesis of aplastic anemia (AA) was explored and the effects of AA serum on the expression of crucial cyclin D isoform (cyclin D3) in umbilical cord blood hematopoietic stem/progenitor cells were observed. The CD34+ cells were isolated from the cord blood with MIDI-MACS Semi-solid methylcellulose culture technique was used to measure the formation of CFU-GM; The expression level of cyclin D3 was assayed by semi-quantitative RT-PCR and Western-blot after the hematopoietic stem/progenitor cells were incubated in AA serum. The results showed that the AA serum could inhibit the formation of CFU-GM and down regulate the expression level of the cyclin D3 at the mRNA and protein level respectively. In conclusion, the AA serum could inhibit the proliferation of hematopoietic stem cells and down regulate level of cyclin D3, which might be one mechanism of hematopoiesis inhibition in AA.
Anemia, Aplastic/*blood ; Antigens, CD34/*metabolism ; Cells, Cultured ; Colony-Forming Units Assay ; Cyclins/*biosynthesis ; Cyclins/genetics ; Fetal Blood/cytology ; Hematopoietic Stem Cells/*cytology ; Protein Isoforms/biosynthesis ; Protein Isoforms/genetics ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Serum

Nitric oxide (NO) signaling has been one of the most rapidly growing areas of study in biology. We know today that NO acts as a signal molecule in the nervous system, a weapon against infection, a regulator of blood pressure, and a gatekeeper of blood flow to different organs. However, much remains to be determined about the physiological and pathophysiological role of NO in the airways. NO appears to be co-localized to cholinergic innervation and involved in vasomotor and secretomotor control of the nasal mucosa. NO is present in exhaled air and appears to originate mainly from paranasal sinus epithelium. Moreover, immunohistochemical and in situ hybridization studies identify all three known isoforms of NO synthase in nasal mucosa. Inhaled endogenous NO in the airways is suggested as playing a role in host defense, and involved in the regulation of pulmonary function as an 'aerocrine.' However, the role of NO in airway inflammation is complicated and clearly has to be determined. The physiological role of NO in the nasal mucosa and its possible pathophysiological role in rhinitis are to be discussed.
Biology ; Blood Pressure ; Epithelium ; In Situ Hybridization ; Inflammation ; Nasal Mucosa* ; Nervous System ; Nitric Oxide Synthase ; Nitric Oxide* ; Protein Isoforms ; Rhinitis*

PURPOSE: Nitric oxide (NO) is known as the free radical which acts on the relaxation of the vascular smooth muscle. We performed the artificial renal infarction on the ipsilateral renal artery, and investigated the change of expressions of nitric oxide synthase (NOS) isoforms on the contralateral kindey of the rats. MATERIALS AND METHODS: Spraque-Dawley rats (300-350gm) were divided into 2 groups as control group (n=10) and operation group (n=30). Control group was performed sham operation and operation group was ligated the left renal artery with 5-0 silk. At the 1 week after operation, right kidney was obtained and determined expression of nNOS, eNOS and iNOS using immunohistochemical staining and the intensities of expression of NOS isoforms were analyzed with image analyzer. We also checked the blood pressure by tail-cuff method before and 1 week after operation. RESULTS: Average systolic BP was elevated on the operation group significantly. While in the control group, which was 128.7 +/- 1.5mmHg initially, to 127.2 +/- 3.3mmHg 1 week later, in the operation group 123.8 +/- 3.2mmHg to 152.5 +/- 4.3mmHg. The intensities of NOS isoform, only the nNOS in the glomerular area was increased with significance statistically, but eNOS and iNOS were not increased. In tubular area, there were no evidences of increment of the intensities. CONCLUSIONS: These results suggested that when the renal infarction was developed, nNOS which located in the renal glomerular area may has relations with influence on the renal blood flow and renin-angiotensin aldosterone on contralateral kidney. We were convinced that nNOS play a important role of the integral modulator of renovascular message system which result in the renovascular hypertension after all.
Aldosterone ; Animals ; Blood Pressure ; Hypertension, Renovascular ; Infarction* ; Kidney* ; Muscle, Smooth, Vascular ; Nitric Oxide Synthase* ; Nitric Oxide* ; Protein Isoforms* ; Rats* ; Relaxation ; Renal Artery ; Renal Circulation ; Silk

OBJECTIVETo investigate the clinical characteristics and the pattern of precore and core promoter mutations of hepatitis B virus (HBV) subgenotypes Ba, C1 and C2.

METHODSA cohort of 151 patients with chronic HBV infection in Guangdong province of China was enrolled in this study. HBV subgenotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Precore and core promoter mutations were analysed using nucleotide sequencing.

RESULTSOf the 151 patients, 80, 51 and 20 were infected with subgenotypes Ba, C1 and C2 respectively. No significant differences were found in HBeAg positivity and liver functional indexes among these three subgenotypes when age and sex were matched. Virologically, HBV/Ba showed the highest frequency of A1896 mutation but the lowest frequency of T1762/A1764 mutation. HBV/C1 was associated with the highest tendency to develop T1762/A1764 mutation, but the lowest prevalence of A1896 mutation. HBV/C2 was associated with an intermediate tendency to develop A1896 and T1762/A1764 mutations.

CONCLUSIONDifferent mutation patterns in precore and core promoter regions are responsible for HBeAg-negative HBV infections among different subgenotypes.

Adolescent ; Adult ; Aged ; DNA, Viral ; blood ; Female ; Genotype ; Hepatitis B ; classification ; virology ; Hepatitis B virus ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; Protein Isoforms ; Young Adult

BACKGROUND: Increased prevalence of diabetes in recent years is linked with increased cardiovascular morbidity and mortality. Apolipoprotein E (apo E) polymorphism is well known to be related to hyperlipidemia and coronary heart disease, but only a few studies investigated the association between apo E polymorphism and diabetes or insulin resistance. In Korea, two studies with relatively small subjects reported controversial results. Therefore, we investigated the association between apo E polymorphism and diabetes in elderly community population. METHODS: 982 elderly people aged 65 or over in Seongnam city were enrolled. We measured anthropometric variables and blood pressure and performed biochemical tests including fasting glucose, fasting insulin, HbA1c, and lipid profiles. Apo E polymorphism was determined by PCR-RFLP method. RESULTS: Frequencies of apo E isoforms and alleles were similar to those of other reports. Subjects with e4 allele had significantly higher total and LDL-cholesterol levels. However, there were no differences in cholesterol levels between normal subjects and diabetes. Diabetes was not related to apo E polymorphism. CONCLUSION: In Korean aged 65 or over, subjects with diabetes didn't have increased total or LDL-cholesterol, triglyceride, and decreased HDL-cholesterol levels. Diabetes and apo E polymorphism were not related.
Aged ; Alleles ; Apolipoproteins ; Apolipoproteins E ; Blood Pressure ; Cholesterol ; Coronary Disease ; Fasting ; Glucose ; Humans ; Hyperlipidemias ; Insulin ; Insulin Resistance ; Korea ; Prevalence ; Protein Isoforms

Adult ; Asian Continental Ancestry Group ; DNA, Viral ; blood ; Female ; Genes, Viral ; genetics ; Hepatitis B virus ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; Protein Isoforms ; genetics ; Viral Core Proteins ; genetics

Cancer cells are known to show increased rates of glycolysis metabolism. Based on this, PET studies using F-18-fluorodeoxyglucose have been used for the detection of primary and metastatic tumors. To account for this increased glucose uptake, a variety of mechanisms has been proposed. Glucose influx across the cell membrane is mediated by a family of structurally related proteins known as glucose transporters (Gluts). Among 6 isoforms of Gluts, Glut-1 and/or Glut-3 have been reported to show increased expression in various tumors. Increased level of Glut mRNA transcription is supposed to be the basic mechanism of Glut overexpression at the protein level. Some oncogens such as src or ras intensely stimulate Glut-1 by means of increased Glut-1 mRNA levels. Hexokinase activity is another important factor in glucose uptake in cancer cells. Especially hexokinase type II is considered to be involved in glycolysis of cancer cells. Much of the hexokinase of tumor cells is bound to outer membrane of mitochondria by the porin, a hexokinase receptor. Through this interaction, hexokinase may gain preferred access to ATP synthesized via oxidative phosphorylation in the inner mitochondria compartment. Other biologic factors such as tumor blood flow, blood volume, hypoxia, and infiltrating cells in tumor tissue are involved. Relative hypoxia may activate the anaerobic glycolytic pathway. Surrounding macrophages and newly formed granulation tisssue in tumor showed greater glucose uptake than did viable cancer cells. To expand the application of FDG PET in oncology, it is important for nuclear medicine physicians to understand the related mechanisms of glucose uptake in cancer tissue.
Adenosine Triphosphate ; Anoxia ; Biological Factors ; Blood Volume ; Carcinogens ; Cell Membrane ; Glucose* ; Glycolysis ; Hexokinase ; Humans ; Macrophages ; Membranes ; Metabolism ; Mitochondria ; Nuclear Medicine ; Oxidative Phosphorylation ; Protein Isoforms ; RNA, Messenger