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Biomedical subjects

X Han

Publications and source records attributed to X Han.

At least 199 records · Page 11Linked to original sources
PubMed1996

Gastrin-releasing peptide-like immunoreactivity is present in human maternal and fetal placental membranes.

Extracts of human term amnion, placenta, and chorion/decidual tissue (n = 5) contained gastrin-releasing peptide-like immunoreactivity (GRPLI) in amounts of 4.7 +/- 2.9 (pmol/g wet wt; mean +/- SEM), 3.6 +/- 1.1 and 2.9 +/- 1.5, respectively. Using C-terminally directed antisera and gel filtration chromatography and reverse-phase high-performance liquid chromatography (HPLC), each tissue contained molecular forms consistent with the presence of GRP1-27 and GRP18-27 but also contained larger amounts of two GRPLI peaks, which apparently are novel GRP-like peptides. In contrast, tissue extracts of human fetal lung contained only GRP1-27, GRP14-27, and GRP18-27. Using RT-PCR and specific GRP primers and probes, messenger RNA encoding for GRP was readily demonstrable from 6-weeks gestation throughout pregnancy to term in full-thickness membranes, placental villi, and decidua. Positive immunohistochemical staining for GRP occurred in extravillous trophoblasts in decidual septa and fetal membranes, cytotrophoblasts, syncytiotrophoblast, and certain stromal cells in placental villi and amniotic epithelium. GRPLI and GRP messenger RNA were present from the earliest dates examined (6-9 weeks) throughout pregnancy to term. Given the proven trophic nature of GRP and related peptides, these peptides may play important roles in maternal, placental, and fetal development during human pregnancy.

Amnion↗
PubMed1996

Role of conserved peptide in taurine transporter inactivation modulated by protein kinase C.

Activation of protein kinase C (PKC) by the active phorbol ester 12-myristate 13-acetate (PMA, 100 nM) or phorbol-12, 13-dibutyrate (100 nM) reduced taurine uptake by 80% in oocytes given injections with cRNA from and expressing the Madin-Darby canine kidney cell taurine transporter pNCT. Inhibition of PKC by calphostin C or staurosporine increased taurine uptake by 20% and 400%, respectively. The inhibitory effect of PMA on taurine uptake was blocked by calphostin C, a specific inhibitor of PKC. Modulation by PMA mainly affected the apparent affinity K(m) (from 5.6 microM to 18.1 microM) with minimal effect on the maximal velocity (25% decrease) of the transporter. A polyclonal antibody (AbS4) directed against a conserved intracellular segment (S4) of the Madin-Darby canine kidney cell taurine transporter enhanced taurine uptake by pNCT cRNA-treated oocytes. The effect of AbS4 was blocked by incubation with the corresponding peptide antigen. Preimmune IgG and peptide antigen had no effect on taurine transporter activity expressed in oocytes. Modulation seemed to occur through phosphorylation of a consensus PKC site located on segment S4 of the transporter, because downregulation of the transporter by PMA (100 nM) was abolished by preinjection of AbS4 (12 ng/ oocyte). In contrast, downregulation of the transporter by PMA could not be restored by AbS4 when pNCT-expressing oocytes were pretreated with PMA (50 nM). In conclusion, the peptide segment recognized by this antibody appears to participate directly in taurine transporter inactivation that is modulated by PKC phosphorylation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Relationship between chondroitin sulfate proteoglycan and coronary atherosclerosis in the youth.

OBJECTIVE: To study the relationship between chondroitin sulfate proteoglycan (CSPG) and coronary atherosclerosis in youth. MATERIAL AND METHODS: Immunohistochemistry of chondroitin sulfate proteoglycan and SM-alpha-actin was performed on 39 human coronary arteries, including normal vessels and vessels with fatty streaks, intermediate lesions and plaques. Some of the lesional vessels were taken for beta-lipoprotein immunohistochemical study. CSPG contents were quantitated by image analyzer and the coronary arteries from one heart were processed for immunoelectron microscopy. RESULTS: The range of CSPG distribution was extensive and CSPG area density was increased significantly in the intima with atherosclerotic lesions. The increase of CSPG was parallel to the numbers of smooth muscle cell (SMC) with positive SM-alpha-actin reaction and was likely related to the phenotype transformation of SMC. Similar distribution of beta-lipoprotein and CSPG were found within the lesional regions. CONCLUSIONS: The increase of CSPG in atherosclerotic lesion may be an important factor resulting in the deposition of lipids in the vascular wall so as to promote the formation and development of atherosclerosis.

Adolescent↗
PubMed1996

[Emergency contraception with mifepristone and anordrin].

OBJECTIVE: To study the efficacy of mifepristone or with anordrin for emergency contraception. METHODS: 300 healthy women were recruited within 7.2 hours after unprotected intercourse or contraceptive failure and randomly allocated into 3 groups. Group 1 (n = 100), mifepristone 25 mg twice with 12 hours apart; group 2 (n = 99), single dose of mifepristone 25 mg; and group 3 (n = 101), mifepristone 25 mg and anordrine 7.5 mg given once. RESULTS: No pregnancy occurred in group 1, while 1 pregnancy in each group 2 and 3. The contraceptive effectiveness were 100.0%, 83.8% and 86.1% for the 3 groups respectively. The overall menstruation disturbances and side effects were low. CONCLUSIONS: Both mifepristone 50 or 25 mg were effective for emergency contraception and no synergetic effects of anordrin in combination with mifepristone was shown in this study.

Adult↗
PubMed1996

[Inhibitory effects of gypenoside on rat heart and brain Na+, K+(-)ATPase activity].

The effects of gypenoside (Gyp) on the microsomal Na+, K(+)-ATPase from rat hearts and brains were investigated in comparison with ginsenoside (Gin). The results showed that Gyp could inhibit the enzyme activity rapidly and reversibly in vitro. The inhibition was in a concentration-depend manner. The IC50 of Gyp for the heart and brain was 58.79 +/- 8.05 mg/L and 52.07 +/- 6.25 mg/L, respectively. Kinetic analysis revealed that Gyp was an incompetitive inhibitor of ATP. These results suggest that the positive inotrope effect and the inhibition of CNS by Gyp are related to the in hibitory action of Gyp on the actiyily of Na+, K(+)-ATPase from hearts or brains.

Animals↗
PubMed1995

Pre- and post-translational regulation of lysyl oxidase by transforming growth factor-beta 1 in osteoblastic MC3T3-E1 cells.

The final enzymatic step required for collagen cross-linking is the extracellular oxidative deamination of peptidyl-lysine and -hydroxylysine residues by lysyl oxidase. A cross-linked collagenous extracellular matrix is required for bone formation. The goals of this study were to compare the transforming growth factor (TGF)-beta 1 regulation of lysyl oxidase enzyme activity and steady state mRNA levels to changes in COL1A1 mRNA levels in MC3T3-E1 osteoblastic cells. TGF-beta 1 increased steady state lysyl oxidase and COL1A1 mRNA levels in a dose- and time-dependent manner. The increase in lysyl oxidase mRNA levels was transient, peaking at 12 h and 8.8 times controls in cells treated with 400 pM TGF-beta 1. COL1A1 steady state mRNA levels increased maximally to 3.5-fold of controls. Development of increased lysyl oxidase enzyme activity was delayed and was of slightly lower magnitude than the increase in its mRNA levels. This suggested limiting post-translational processing of lysyl oxidase proenzyme. Pulse-labeling/immunoprecipitation studies demonstrated slow proenzyme secretion and proteolytic processing. Development and application of an independent assay for lysyl oxidase proenzyme proteolytic processing activity verified its proportionately lower stimulation by 400 pM TGF-beta 1. Thus, lysyl oxidase regulation by TGF-beta 1 in osteoblastic cell cultures occurs at both pre- and post-translational levels. This regulation is consistent with increased production of a collagenous extracellular matrix.

3T3 Cells↗
PubMed1995

Ligand-directed retroviral targeting of human breast cancer cells.

We explored the feasibility of designing retroviral vectors that can target human breast cancer cells with characteristic receptors via ligand-receptor interaction. The ecotropic Moloney murine leukemia virus envelope was modified by insertion of sequences encoding human heregulin. Ecotropic virus, which normally does not infect human cells, when pseudotyped with the modified envelope protein now crosses species to infect human breast cancer cell lines that overexpress HER-2 (human epidermal growth factor receptor; also called ERBB2) and HER-4 (also called ERBB4), while human breast cancer cell lines expressing low levels of these receptors remain resistant to infection. Since about 20% of human breast cancers overexpress HER-2 and some of breast cancer cell lines overexpress both HER-2 and HER-4, cell-specific targeting of retroviral vectors may provide a different approach for in vivo gene therapy of this type of breast cancer.

Breast Neoplasms↗
PubMed1995

Nitric oxide-dependent parasympathetic signaling is due to activation of constitutive endothelial (type III) nitric oxide synthase in cardiac myocytes.

Nitric oxide synthase (NOS) isoforms are discovered in an increasing variety of cell types with different roles in signaling. The inducible NOS (i.e. iNOS or NOS II) is expressed in cardiac myocytes in response to specific cytokines. Independent of iNOS induction, however, receptor-dependent signaling is modulated by a constitutive nitric oxide (NO) synthase isoform in these cells (Balligand, J. L., Kelly, R.A., Marsden, P.A., Smith, T. W., and Michel, T. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 347-351). We now show that cardiac myocytes constitutively express the endothelial isoform of NO synthase (ecNOS or NOS III). Transcripts for NOS III were detected by Northern blot in myocyte extracts using as a probe a polymerase chain reaction-generated cDNA amplified with isoform and species-specific primers. In subcellular fractionation experiments, a calcium-sensitive NO synthase activity was present primarily in the particulate fraction, coinciding with the distribution of NOS III analyzed by protein immunoblotting. The localization of NOS III within cardiac myocytes was further demonstrated by immunohistochemistry. The functional role of NOS III was explored by analyzing the effects of NOS inhibitors on single myocyte L-type calcium current and contractility. Inhibition of NOS blocked the attenuation by carbamylcholine of the increases in both parameters induced by beta-adrenergic stimulation. We conclude that NO-dependent parasympathetic signaling is mediated by NOS III in cardiac myocytes.

Amino Acid Oxidoreductases↗
PubMed1995

Collagen synthesis and types I, III, IV, and VI collagens in an animal model of disc degeneration.

STUDY DESIGN: The present study sought to elucidate the changes that occur in collagen chemistry in the early phases of disc degeneration. OBJECTIVE: To monitor the healing process of the injured anulus fibrosus and the secondary degenerative reactions in the nucleus pulposus. SUMMARY OF BACKGROUND DATA: Despite the importance of collagen chemistry under pathologic conditions in the intervertebral disc, knowledge of this aspect is very limited. METHODS: Fourteen pigs were stabbed with a scalpel blade in the anterior part of the anulus fibrosus of a lumbar disc. The animals were killed 2 weeks to 5 months after injury. The activities of prolyl 4-hydroxylase and galactosylhydroxylysyl glucosyltransferase, the total collagen content, and staining patterns for Types I, III, IV, and VI collagens were analyzed from different parts of the disc. RESULTS: The most active phase of the healing process, assessed from the activities of enzymes involved in collagen biosynthesis, took place during the first month postoperatively. The anular lesion was found to cicatrize through formation of disorganized granulation tissue in which Type I, III, and, IV collagens were deposited. In the nucleus pulposus, activities of prolyl 4-hydroxylase and galactosylhydroxylysyl glucosyltransferase and total collagen content increased, and the originally rounded cells became more elongated, resembling fibroblasts. CONCLUSIONS: The results of this study suggest that the altered composition of collagens observed in the degenerate porcine nucleus pulposus results from changes in cell phenotype: Notochondral cells were replaced by fibroblast-like cells. It is likely that trauma to the anulus fibrosus can initiate a progressive degenerative process in the disc tissue.

Animals↗
PubMed1995

Induction of immunocellular resistance to IL-2-activated lymphocytes within ovarian carcinoma cells.

The development of resistance within ovarian carcinoma cells to activated cytotoxic lymphocytes was the objective of this study. Primary ovarian carcinoma cells were obtained from the ascites of a patient. These cells were cocultured with IL-2-activated autologous tumor-associated lymphocytes (TALs) for 1 week. The resulting selected cells underwent a second coculture for 3 days with IL-2-activated autologous TALs or tumor-infiltrating lymphocytes (TILs). Phenotype analysis of the lymphocytes was performed prior to selection and 4-hr chromium release assays were used to detect resistance induction. Resistance to all effector cells could be demonstrated for the selected cells. However, selected cells maintained in culture demonstrated no difference in cytotoxic susceptibility from unselected cells. The following conclusions were made: (i) rapid immunoselection can occur for ovarian carcinoma in vitro; (ii) the resistance induced is not MHC-restricted; (iii) resistance induced by one type of cytotoxic cell results in general resistance to other types of cell from the same patient; and (iv) this resistance is not maintained during in vitro culture. These results may have direct implications on the future immunotherapy for this condition.

Cells, Cultured↗
PubMed1995

Clinical application of modified Anyang type 2 esophageal intubation instrument--a new esophageal intubation method.

The preliminary experience in the clinical use of Anyang Type 2 esophageal intubation instrument, designed by ourselves, in 11 patients with severe esophageal obstruction due to advanced carcinoma of the esophageal was reported. The diagnosis of all 11 cases was confirmed by barium-meal roentgenography. After intubation, all the patients could take liquid or soft diet by mouth. There was no operative mortality and the patients survived 2 to 14 months (mean 5.7 months). All of them could take food by mouth before death. The clinical application proved that the intubation has been a safe and suitable management.

Adult↗
PubMed1995

A cellular mechanism for nitric oxide-mediated cholinergic control of mammalian heart rate.

The biochemical signaling pathways involved in nitric oxide (NO)-mediated cholinergic inhibition of L-type Ca2+ current (ICa[L]) were investigated in isolated primary pacemaker cells from the rabbit sinoatrial node (SAN) using the nystatin-perforated whole-cell voltage clamp technique. Carbamylcholine (CCh; 1 microM), a stable analogue of acetylcholine, significantly inhibited ICa(L) after it had been augmented by isoproterenol (ISO; 1 microM). CCh also activated an outward K+ current, IK(ACh). Both of these effects of CCh were blocked completely by atropine. Preincubation of the SAN cells with L-nitro-arginine methyl ester (L-NAME; 0.2-1 mM), which inhibits NO synthase (NOS), abolished the CCh-induced attenuation of ICa(L) but had no effect on IK(ACh). Coincubation of cells with both L-NAME and the endogenous substrate of NOS, L-arginine (1 nM), restored the CCh-induced attenuation of ICa(L), indicating that L-NAME did not directly interfere with the muscarinic action of CCh on ICa(L). In the presence of ISO the CCh-induced inhibition of ICa(L) could be mimicked by the NO donor 3-morpholino-sydnonimine (SIN-1; 0.1 mM). SIN-1 had no effect on its own or after a maximal effect of CCh had developed, indicating that it does not inhibit ICa(L) directly. SIN-1 failed to activate IK(ACh), demonstrating that it did not activate muscarinic receptors. Both CCh and NO are known to activate guanylyl cyclase and elevate intracellular cGMP. External application of methylene blue (10 microM), which interferes with the ability of NO to activate guanylyl cyclase, blocked the CCh-induced attenuation of ICa(L). However, it also blocked the activation of IK(ACh), suggesting an additional effect on muscarinic receptors or G proteins. To address this, a separate series of experiments was performed using conventional whole-cell recordings with methylene blue in the pipette. Under these conditions, the CCh-induced attenuation of ICa(L) was blocked, but the activation of IK(ACh) was still observed. Methylene blue also blocked the SIN-1-induced decrease in ICa(L). 6-anilino-5,8-quinolinedione (LY83583; 30 microM), an agent known to decrease both basal and CCh-stimulated cGMP levels, prevented the inhibitory effects of both CCh and SIN-1 on ICa(L), but had no effect on the activation of IK(ACh) by CCh. In combination, these results show that CCh- and NO-induced inhibition of ICa(L) is mediated by cGMP.(ABSTRACT TRUNCATED AT 400 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1995

Microsome-mediated 8-hydroxylation of guanine bases of DNA by steroid estrogens: correlation of DNA damage by free radicals with metabolic activation to quinones.

Free radical generation by metabolic redox cycling between catechol estrogens and their quinones and subsequent hydroxyl radical damage to DNA have been proposed to mediate estrogen-induced renal carcinogenesis in the hamster. In this study the content of 8-hydroxy-2'-deoxy-guanosine (8-OHdG), a marker product of hydroxyl radical action, was examined in DNA incubated with a liver microsomal activating system and with catechol estrogens, equilenin-3,4-quinone or with parent estrogens. Equilenin-3,4-quinone increased the formation of 8-OHdG by 50% over control levels. 4-Hydroxyestrone and 4-hydroxy-estradiol raised 8-OHdG contents significantly, to 1.61 +/- 0.79 and 1.27 +/- 0.31 8-OHdG/10(5) deoxyguanosine (dG) respectively over controls (0.68 +/- 0.25 8-OHdG/10(5) dG). The corresponding 2-hydroxylated estrogens and the parent hormones estrone, estradiol and equilenin did not affect 8-hydroxylation of guanine bases of DNA. In incubations of catechol estrogens with microsomes and cumene hydroperoxide the 4-hydroxyestrogens were oxidized to quinones more rapidly than the 2-hydroxyestrogens. Our data support a mechanism of hydroxyl radical generation from estrogens by redox cycling between 4-hydroxylated metabolites and their quinones. The rapid oxidation of 4-hydroxylated estrogens to quinones, their redox cycling and hydroxyl radical damage to DNA is consistent with the previously reported carcinogenic activities of 4-hydroxylated, but not of 2-hydroxylated, catechol estrogens.

Animals↗
PubMed1995

Induction of a DNA adduct detectable by 32P-postlabeling in the dorsolateral prostate of NBL/Cr rats treated with estradiol-17 beta and testosterone.

Treatment with estradiol-17 beta and testosterone induces epithelial dysplasia and, subsequently, adenocarcinoma in the dorsolateral prostate of NBL rats. The purpose of this study was to determine whether this carcinogenic effect is mediated by genotoxicity. Analogous to adducts produced by estrogens in the male hamster kidney, a target of estrogen carcinogenicity, induction of DNA adducts detectable by 32P-postlabeling was investigated in the prostate target tissue. NBL rats were treated with separate Silastic tubing implants containing testosterone and estradiol-17 beta. Control animals received empty implants. Animals were killed at 8, 16 and 24 weeks after initiation of treatment, and accessory sex glands were sampled for adduct analysis. DNA of the dorsolateral and ventral prostate and the coagulating gland (= anterior prostate) was isolated and analyzed by nuclease P1-enhancement of the 32P-post-labeling assay. DNA adducts were quantitated by Cerenkov counting. An adduct occurred selectively in DNA of the dorsolateral prostate of rats treated with estradiol plus testosterone for 16 or 24 weeks with relative adduct level values of approximately 10 x 10(9), but not in DNA of the ventral or anterior prostate. The adduct was not present in DNA of prostate tissue of rats treated for 8 weeks or in DNA of control tissues. This adduct was unique with respect to chromatographic location and has not been observed before in any tissue of control or hormone-treated animals. Neither the structure of the treatment-induced adduct nor the mechanism of its formation is known. However, the selective occurrence of this adduct in the tissue of origin of the carcinomas and its appearance coinciding with putative preneoplastic lesions and preceding carcinoma development suggests a causal relation between adduct formation and prostate cancer development in testosterone plus estradiol-17 beta-treated rats.

Adenocarcinoma↗
PubMed1995

Effects of streptozotocin-induced diabetes, physical training and their combination on collagen biosynthesis in rat skeletal muscle.

The effects of streptozotocin-induced diabetes, physical training and their combination on the activities of prolyl 4-hydroxylase (PH) and galactosylhydroxylysyl glucosyl-transferase (GGT), both marker enzymes of collagen biosynthesis, and on the concentration of hydroxyproline (Hyp) were studied in vastus lateralis, rectus femoris and gastrocnemius muscles in rats. The experimental period was 12-16 weeks. Diabetes had an overall decreasing effect on specific PH activity in all muscles studied, whereas specific GGT activity remained at control level. Total PH and GGT activities decreased in all three muscles in the diabetic animals (P < 0.001). Training caused an increase in PH and GGT activities in gastrocnemius in non-diabetic rats, whereas training in combination with diabetes did not change specific PH or GGT activity. Diabetes increased specific Hyp concentration in vastus lateralis and gastrocnemius in trained diabetic rats (P < 0.05), whereas training decreased Hyp level significantly (P < 0.05) in vastus lateralis in non-diabetic rats, but not in diabetic animals. The results suggest that in streptozotocin-induced diabetes the decrease in collagen synthesis rate exceeds the negative total protein balance in the muscle. Although physical training may have an increasing effect on muscular collagen synthesis in non-diabetic rats, it is unable to prevent the decreasing effect of diabetes on collagen synthesis.

Animals↗
PubMed1995

Immunohistochemical localisation of steroidogenic enzymes and phenylethanolamine-N-methyl-transferase (PNMT) in the adrenal gland of the fetal and newborn foal.

An increase in fetal adrenal cortisol output signals the onset of parturition in many animal species but, in the fetal horse, plasma concentrations of cortisol remain low for much of late pregnancy, with a rise occurring only very close to the time of birth (term 320-360 days). Immunohistochemistry was used to determine the localisation and changes in distribution of key steroidogenic enzymes for cortisol production; P450scc, P450C17 and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) in adrenal tissue from fetal and newborn horses and these findings were correlated with the appearance of immunoreactive (IR)-phenylethanolamine-N-methyl-transferase (PNMT), a cortisol-dependent enzyme. Five micron sections of adrenal tissue from fetuses at Day 100-156 (n = 5), Day 244-295 (n = 8), greater than Day 300 (n = 4) and from newborn foals (n = 6), were stained using specific antibodies and the avidin-biotin-peroxidase technique. All 3 steroidogenic enzymes were present by Day 150, but in less than 20% of the cortical cells. By late gestation the steroidogenic enzymes were present in approximately 30% of the cells, but the distribution varied. P450SCC and P450C17 predominated in cortical cells proximal to the medulla; 3 beta HSD was present throughout the cortex, but more in the zona fasciculata. In foals after birth, IR-3 beta HSD and IR-P450SCC had increased substantially throughout the adrenal cortex, and IR-P450C17 was present in most cells of the presumptive zonae fasciculata and reticularis. IR-PMNT was localised to nuclei of scattered medullary cells at the medullary-cortical interface by Day 150.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

Localisation of 15-hydroxy prostaglandin dehydrogenase (PGDH) and steroidogenic enzymes in the equine placenta.

15-hydroxy prostaglandin dehydrogenase (PGDH) is the critical enzyme that determines metabolism of primary prostaglandins. Its expression is determined in part by steroid hormones, particularly progesterone, formed from delta(5) steroids through 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity. To assess whether the regulation of PGDH might occur in a paracrine, autocrine or intracrine fashion, we used immunohistochemistry (IHC) to determine the localisation of key steroidogenic enzymes in the equine placenta and compared these patterns to the distribution of immunoreactive (IR-) PGDH. Placental tissue was obtained from pony or Thoroughbred mares at about Days 150, 250-280 and >300 of pregnancy (term 320 to 360 days; n=5-8 each group). IR-PGDH, 3beta-HSD, cholesterol side chain cleavage enzyme (P450(scc)) and 17-hydroxylase/lyase (P450(C17)) were localised using specific antibodies and the avidin-biotin peroxidase technique and visualised using diaminobenzidine as substrate. IR-P450(scc) was present in trophoblast cells, but not in maternal tissues of the microcotyledons. In contrast, at Days 150 and 280, IR-PGDH was present in maternal epithelial and interstitial cells in the microcotyledons, but was not detected in trophoblast epithelium, chorioallantois or endometrial glands. After Day 300, IR-PGDH was present in the maternal epithelium and interstitial cells of the placenta and it was also present in trophoblast cells in some specimens.

3-Hydroxysteroid Dehydrogenases↗