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*

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

To explore the hematopoiesis inhibition mechanisms of interferon-gamma (IFN-gamma), the effects of IFN-gamma on the expression of the cyclin D in the umbilical cord blood hematopoietic stem/progenitor cells were observed. In the experiments the CD34(+) cells were isolated from the cord blood with MIDI-MACS system; semi-solid methylcellulose culture technique was used to measure the formation of CFU-GM; the expression levels of cyclin D isoforms were assayed by semi-quantitative RT-PCR, after the hematopoietic stem/progenitor cells were incubated with IFN-gamma. The results indicated that IFN-gamma could inhibit the formation of CFU-GM and down-regulate the expression of cyclin D2 and cyclin D3 at the mRNA level. It is concluded that the IFN-gamma could inhibit the proliferation of hematopoietic stem cells and down-regulate the expression of cyclin D, that may be one mechanism underlying the hematopoietic inhibition of IFN-gamma.
Cyclin D ; Cyclins ; genetics ; Fetal Blood ; cytology ; G1 Phase ; Hematopoietic Stem Cells ; drug effects ; metabolism ; Humans ; Interferon-gamma ; pharmacology ; Protein Isoforms ; RNA, Messenger ; analysis

OBJECTIVETo investigate subtype and genetic analysis of human immunodeficiency virus type-1 (HIV-1).

METHODSDNA sequences were amplified by nested-PCR from uncultured peripheral blood mononuclear cells (PBMC) obtained from 100 HIV-1 patients from Guangdong Province. The C2 to V3 region of the envelope glycoprotein gp120 of HIV-1 was sequenced directly. The analysis of the gene-based phylogenetic tree and variation of amino acid were carried out by using Wisconsin software package or genetics computer group (GCG).

RESULTSDNA fragments were amplified from 75 PBMC samples by using nested polymerase chain reaction (PCR). Sequence analysis showed that there were 3 HIV-1 subtypes or circulating recombinant forms (CRF): CRF01-AE (n = 44), CRF-BC (n = 27) and B' (n = 4).

CONCLUSIONSThree HIV-1 subtypes or circulating recombinant forms: CRF01-AE, CRF-BC and B' might be circulating in Guangdong Province. Findings from this study suggested that several subtypes might exist in Guangdong Province and the epidemic situation of AIDS be serious. It should be a challenge for Guangdong Province in treating patients, preventing and controlling AIDS in the future.

Acquired Immunodeficiency Syndrome ; blood ; epidemiology ; virology ; Adolescent ; Adult ; Base Sequence ; Child ; China ; epidemiology ; DNA, Viral ; Female ; HIV-1 ; classification ; genetics ; Humans ; Male ; Middle Aged ; Protein Isoforms

BACKGROUNDHemangiomas are the most common tumors in children. Some hemangiomas may require intervention because of their location, size, behavior, or potential for important complications. Pharmacological therapy with glucocorticoids is the mainstay treatment, but there is no consensus on therapeutic regimens or candidate selection, therapeutic efficacy varies, and the mechanism mediating the beneficial effects of glucocorticoids remains unclear. This study was performed to investigate the expression patterns of the glucocorticoid receptor (GR) and its alpha isoform (GRalpha) in cutaneous hemangiomas and vascular malformations.

METHODSSP immunohistochemical technique was used to examine the expression of GR(e-20) (GR) and GR(p-20) (GRalpha) on vascular endothelial cells in 80 specimens that included 33 proliferating hemangiomas, 32 involuting hemangiomas, 7 vascular malformations as well as 8 normal skin tissues, all obtained from infants and children. GR and GRalpha expression in prepared tissue slides were examined using automated computer-assisted microscopic analysis. Mean gray scale values were compared among the various tumor types.

RESULTSThe mean gray scale values of GR were 127.0 +/- 6.4 and 121.4 +/- 6.6 in hemangiomas and vascular malformations respectively, but this difference was not statistically significant (P = 0.104). However, these values were all markedly higher than that of normal skin, which was only 108.6 +/- 6.8 (P = 0.001 and P = 0.000 for comparison with hemangiomas and vascular malformations respectively). The gray scale of GR in proliferation and involuting hemangiomas were 127.9 +/- 4.8 and 126.0 +/- 5.8 respectively, but this difference was not significant (P = 0.146). However, GRalpha expression in hemangiomas, vascular malformations and normal skin declined gradually in stepwise fashion (127.3 +/- 5.4, 120.4 +/- 6.1 and 109.9 +/- 5.3 respectively; P < 0.001). GRalpha expression was higher in proliferating hemangiomas than in involuting hemangiomas (127.2 +/- 6.3 and 122.5 +/- 6.3; P = 0.004).

CONCLUSIONSGR and GRalpha are strongly expressed in hemangiomas and vascular malformations. The expression of GRalpha is closely related to the phase of the hemangioma. Determination of GR and GRalpha may be a positive significance to understand the information of hemangiomas and vascular malformations and may further help determining proper strategies of steroid therapy for hemangiomas and vascular malformations.

Blood Vessels ; abnormalities ; Child ; Child, Preschool ; Female ; Hemangioma ; chemistry ; pathology ; Humans ; Immunohistochemistry ; Infant ; Male ; Protein Isoforms ; Receptors, Glucocorticoid ; analysis ; Skin Neoplasms ; chemistry ; pathology