It is known that in animals with increased intracranial pressure the cerebral perfusion is curtailed, but whether it is caused by deranged responsiveness of the cerebral vessel is not known. Thus, it was attempted in this study to find out the changes of cerebrovascular response to Kallikrein in the rabbits with increased ICP(20mmHg) under urethane-anesthesia. 1) intracarotid arterial kallikrein elicited increases in cerebral blood flow and decreases in blood pressure and arterial resistance. 2) Cerebral blood flow was significantly decreased in rabbits with increased ICP in comparison with the control rabbits. 3) Intraarterial kallikrein caused dose-depent increases of cerebral blood flow in both groups, but responses were significantly reduced in ICP-elevated group. 4) Kallikrein produced dose-dependent hypotensive effect in both groups with no significant difference between both groups. 5) Cerebrovascular resistance was greater in rabbits with elevated ICP(20 mmHg), but kallikrein induced decreases of cerebrovascular resistance in both groups to the same degree, 6) Above results suggested that increased ICP reduces the cerebral blood flow by increasing cerebrovascular resistance, but it does not modify the reponsiveness of cerebral vessel to kallikrein.
Animals ; Blood Pressure ; Intracranial Pressure ; Kallikreins* ; Perfusion ; Rabbits*

Kallikrein preparation have already been accepted as therapeutic for male infertility. Especially oral Kallikrein therapy exerted a favorable effect on sperm motility in oligozoospermia and asthenozoospermia. We have carried out a Similar clinical examination of the effect of kallikrein taken orally 60 KU per day for 3-9 months, on the qualitative increase of motile spermatozoa in normogonadotropic infertile males with l0 idiopathic oligozoospermia (less than 20 x 10(6)/ml), 10 idiopathic asthenozoospermia (less then 20% of sperm motility) and 8 idiopathic asthenozoospermia entered the study as control placebo treatment group. Number of spermatozoa increased more than 30% of basic levels (over 30 x 10(6)/ml) in the 2 patient(20 %) and pregnancy occurred in the l patient (10%) out of the 10 patients with idiopathic oligozoospermia after the kallikrein therapy. In these 2 patients responded, the sperm concentration changed from 15.4 x 10(6)ml to 43.0 x 10(6)/ml. Sperm motility improved more than 20% in the 3 patients (30%) and pregnancy occurred in the 2 patients (20%) out of the 10 idiopathic asthenozoospermia after the therapy. In these 3 patients improved, the sperm motility changed from l3.2% to 43.5%. Sperm motility was increased only 1 patient (12.5%) out of the 8 placebo treatment control group and no pregnancy occurred to a side effect of kallikrein.
Asthenozoospermia* ; Humans ; Infertility ; Infertility, Male ; Kallikreins* ; Male ; Oligospermia ; Pregnancy ; Sperm Motility* ; Spermatozoa*

Some investigators suggest that the pancreatic proteinase kallikrein plays an important role in the regulation of spermatozoal motility. Particularly, oral kallikrein therapy exerted a favorable effect on Sperm motility in oligozoospermia and asthenozoospermia. We have carried out a similar clinical investigation of the efficacy of kallikrein, taken orally 60 kU per day for 3-9 months, on the quantitative and qualitative motility of spermatozoa in normogonadotropic infertile men. with 15 idiopathic oligozoospermia and 18 idiopathic asthenozoospermia. Number of spermatozoa increased more than double number of basic levels (over 40 x 10(6)/ml) in the 5 patients (33%) and pregnancy occurred in the 3 patients (20%) out of the 15 patients with idiopathic oligozoospermia (less than 20 x 10(6)/ml) after the kallikrein therapy. In these responded 5 patients, the sperm concentration changed from 13.6 x 10(6)/ml to 54.0 x 10(6)/ml, Motility and viability of spermatozoa improved more than 30% in the 5 patients (28%) and pregnancy occurred in the 2patients (11%) out of the 18 patients with idiopathic asthenozoospermia (less than 20% of sperm motility) after the therapy. In these. improved 5 patients, the sperm motility changed from 9.0% to 45.0%. No remarkable side effect was detected.
Asthenozoospermia ; Humans ; Infertility, Male* ; Kallikreins ; Male ; Male* ; Oligospermia ; Pregnancy ; Research Personnel ; Semen* ; Sperm Motility ; Spermatozoa

Some investigators suggest that the pancreatic proteinase kallikrein plays an important role in the regulation of spermatozoal motility. Particularly, oral kallikrein therapy exerted a favorable effect on Sperm motility in oligozoospermia and asthenozoospermia. We have carried out a similar clinical investigation of the efficacy of kallikrein, taken orally 60 kU per day for 3-9 months, on the quantitative and qualitative motility of spermatozoa in normogonadotropic infertile men. with 15 idiopathic oligozoospermia and 18 idiopathic asthenozoospermia. Number of spermatozoa increased more than double number of basic levels (over 40 x 10(6)/ml) in the 5 patients (33%) and pregnancy occurred in the 3 patients (20%) out of the 15 patients with idiopathic oligozoospermia (less than 20 x 10(6)/ml) after the kallikrein therapy. In these responded 5 patients, the sperm concentration changed from 13.6 x 10(6)/ml to 54.0 x 10(6)/ml, Motility and viability of spermatozoa improved more than 30% in the 5 patients (28%) and pregnancy occurred in the 2patients (11%) out of the 18 patients with idiopathic asthenozoospermia (less than 20% of sperm motility) after the therapy. In these. improved 5 patients, the sperm motility changed from 9.0% to 45.0%. No remarkable side effect was detected.
Asthenozoospermia ; Humans ; Infertility, Male* ; Kallikreins ; Male ; Male* ; Oligospermia ; Pregnancy ; Research Personnel ; Semen* ; Sperm Motility ; Spermatozoa

Aged ; Humans ; Kallikreins ; analysis ; Male ; Middle Aged ; Prognosis ; Prostate-Specific Antigen ; analysis ; Prostatic Neoplasms ; diagnosis

OBJECTIVETo investigate the influence of stromal cells on the Kallikrein 7 (KLK7) expression of epithelial cells in benign prostate hyperplasia (BPH).

METHODSWe constructed a stromal-epithelial co-culture model after separating the two types of cells from BPH tissues and identifying them by cell morphology and chemiluminescent microparticle immunoassay (CMIA). The expression of KLK7 mRNA was detected by RT-PCR in the epithelial cells with or without the stromal cells, and that of the KLK7 protein (hK7) determined by Western blot.

RESULTSStromal and epithelial cells were successfully separated and identified, and a stromal-epithelial co-culture model successfully established. RT-PCR showed that the mRNA expression of the KLK7 gene was higher in the epithelial cells co-cultured with stromal cells than in the epithelial cells alone, and the gray value of KLK7 to GAPDH was 1.41 +/- 0.041 in the former and 1.78 +/- 0.10 in the latter (P < 0.01). The results of Western blot were consistent with those of RT-PCR.

CONCLUSIONStromal cells can suppress the expression of the KLK7 gene in the epithelial cells in BPH. KLK7 may be involved in the change of epithelial cells stimulated by stromal cells.

Cells, Cultured ; Humans ; Kallikreins ; metabolism ; Male ; Prostate ; metabolism ; Prostatic Hyperplasia ; metabolism ; pathology ; Stromal Cells ; metabolism

OBJECTIVETo investigate the potential correlation between the single nucleotide polymorphisms (SNPs) in the KLKB1 region and pulmonary thromboembolism(PTE) in a Chinese Han population.

METHODSIn this case-control study, 95 patients with confirmed PTE were enrolled as the PTE group and 90 healthy subjects as the control group. The genotypes, alleles, and haplotypes of the SNPs were analyzed with PLINK 1.07 and Haploview 4.2 software using chi-square test and Logistic regression analysis. SNPs were further analyzed under three genetic models (additive, dominant, and recessive).

RESULTSThe distribution of rs3733402 in KLKB1 gene showed significant difference between PTE group and control group (P=0.041). The distributions of GTG haplotypes consisted of rs2292423, rs4253325,and rs3733402 in KLKB1 gene were also significantly different between PTE group and control group(P=0.040).

CONCLUSIONThe rs3733402 locus variation in KLKB1 gene is associated with PTE in Chinese Han people.

Alleles ; Case-Control Studies ; Chi-Square Distribution ; Genotype ; Haplotypes ; Humans ; Kallikreins ; Polymorphism, Single Nucleotide ; Pulmonary Embolism

The involvement of plasma kallikrein-kinin system in some pathological states such as bronchial asthma and coughing induced by captopril has been suggested, LTC, and LTD, have been well reported to have a potent activity of bronchoconstriction and mucous secretion. The author tried to confirm whether leukotrienes increase glandular kallikrein activity in bronchial wash or not, and if it is true, to investigate the possible mechanism of leukotrienes-induced increase of glandular kallikrein activity. Bronchial wash was collected from excised lungs of guinea pig, and incubated with synthetic substrate (Pro-Phe-Arg-MCA), and released amount of AMC was measured by fluorescence spectrophotometer as the amidase activity (glandular kallikrein activity). In order to confirm that glandular kallikrein can release kinin, bronchial wash was also incubated with purified LMW- kininogen in the presence of kininase inhibitor (o-phenanthroline), and the amount of kinin was measured by enzyme immunoassay as the kinin releasing activity of glandular kallikrein. The results were as follows: 1) The glandular kallikrein activity (control: 2.98 x 10(-11) mole/min/ml wash) was increased by pilocarpine (12-120 umole/kg, i.v.), and the increased glandular kallikrein activity by pilocarpine (41 nmole/kg, i.v.) was inhibited by atropine (4-43 nmole/kg, i.v.). 2) LTC(4) (1-10 nmole/kg, i.v.) or LTD(4) (1-10 nmole/kg, i.v.) increased the glandular kallikrein activity, but the potency of LTD, was about 1/3 of that of LTC,. The increased glandular kallikrein activity by LTC, (3 nmole/kg, i.v.) was inhibited by ONO-1078 (20-203 nmole/kg, i.p.). 3) The increased glandular kallikrein activity by LTC, (3nmole/kg, i.v.) was inhibited by in- domethacin (8-83 nmole/kg, i.p.), OKY-046 (11-113 nmole/kg, i.v.), atropine (4-43 nmole/kg, i.v.), scopolamine (9-88 umole/kg, i.v.) and Thi-D-Phe-BK (100-1000 nmole/kg, i.v.). 4) STA, (6-60pmole/kg, i.v.) increased the glandular kallikrein activity, and the increased glandular kallikrein activity by STA, (20 pmole/kg, i.v.) was inhibited by atropine (14 umole/kg, i.v.) (p < 0. 001). 5) The increased glandular kallikrein activity by pilocarpine (41 urnole/kg, i.v.) was not inhibited by indomethacin (83 umole/kg, i.p.), but it was inhibited by Thi-D-Phe-BK (300 nmole/kg, i.v.) (p< 0. 001). 6) Bradykinin (3-30 nmole/kg, i.v.) increased the glandular kallikrein activity, and the increased glandular kallikrein activity by bradykinin (30 nmole/kg, i.v.) was inhibited by indomethacin (83 umole/kg, i.p.) or atropine (14 umole/kg, i.v.) (p<0.001). 7) The kinin releasing activity by glandular kallikrein in bronchial wash was 24 x 10 " mole/min/ ml wash in control group, and it was markedly increased in pilocarpine-pretreated group (124 x 10 mole/min/ml wash) (p<0.05), and in LTC4-pretreated group (164x10 mole/min/ml wash) (p<0. 01). The increased kinin releasing activity by LTC, (3 nmole/kg, i.v.) was completely inhibited by aprotinin (5000IU/ml, i.v.). I could conclude that i ) LTC, and LTD, increased glandular kallikrein activity in bronchial wash of guinea pig, ii) the most possible mechanism of LTC,-induced increase of glandular kallikrein activity in bronchial wash may be as follows; LTC,TXA,aeetyleholineinerease of glandular kallikrein acitivity, and iii) kinin released by glandular kallikrein may enhance the action of TXA, or acetylcholine to increase the glandular kallikrein activity.
Acetylcholine ; Animals ; Aprotinin ; Asthma ; Atropine ; Bradykinin ; Bronchoconstriction ; Captopril ; Cough ; Fluorescence ; Guinea Pigs* ; Guinea* ; Immunoenzyme Techniques ; Indomethacin ; Kallikrein-Kinin System ; Kallikreins ; Kininogens ; Leukotriene C4* ; Leukotrienes ; Lung ; Pilocarpine ; Plasma ; Scopolamine Hydrobromide ; Tissue Kallikreins*

OBJECTIVETo study the effect of kallikrein-related peptidase 10 (KLK10) on the proliferation and invasiveness of human tongue cancer cell line Tca8113.

METHODSThe eukaryotic expression vector harboring KLK10 gene (pIRES2-EGFP-KLK10) was transfected in Tca8113 cells and the stable cell lines were selected by G418 screening. The mRNA and protein expression of KLK10 in transfected Tca8113 cells were assayed by RT-PCR and Western blotting, respectively, and the proliferation and invasiveness of the cells were evaluated by MTS cell growth assay and Transwell chamber invasion experiments.

RESULTSA stable Tca8113 cell line with high KLK10 expression was obtained, which showed significantly increased mRNA and protein expression levels of KLK10 and obviously attenuated proliferation and invasiveness compared with control and empty vector-transfected cells (P<0.05).

CONCLUSIONEnhancing KLK10 gene expression can decrease the proliferation and invasiveness of human tongue cancer cells in vitro.

Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Genetic Vectors ; Humans ; Kallikreins ; genetics ; Tongue Neoplasms ; genetics ; pathology

PURPOSE: Involvement of human kallikreins (hKs) in human cancers has been reported and several hKs are promising biomarkers of various cancers. The aim of this study was to evaluate the prognostic significance of hK11 expression in patients with non-metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The study included 44 patients with NSCLC. hK11 expression was determined by immunohistochemical staining. RESULTS: The estimation of disease-free and overall survival by Kaplan-Meier was 11 months and 17 months, respectively. The estimation of overall survival by Kaplan-Meier was significantly higher in patients with hK11 strongly positive (2+) than in those with hK11 weakly positive (1+) (20 months vs. 11 months, p=0.032). Although not statistically different, the estimation of disease-free survival by Kaplan-Meier was higher in patients with hK11 strongly positive (2+) than in those with hK11 weakly positive (1+) (12 months vs. 9 months, p=0.113). Multivariate Cox regression analysis showed that the overall survival rates were significantly associated with response to chemoradiotherapy and the degree of staining with hK11. CONCLUSION: The stronger hK11 expression in NSCLC appears to be associated with better survival rates. hK11 may be a prognostic biomarker of NSCLC.
Biological Markers ; Carcinoma, Non-Small-Cell Lung* ; Chemoradiotherapy* ; Disease-Free Survival ; Humans* ; Kallikreins* ; Lung Neoplasms ; Survival Rate