Search PubMed⌕ Search

Biomedical subjects

X Luo

Publications and source records attributed to X Luo.

At least 235 records · Page 13Linked to original sources

Increased expression of type 1 angiotensin II receptors in the hypothalamic paraventricular nucleus following stress and glucocorticoid administration.

Double staining in situ hybridization studies have shown that angiotensin II (AII) type 1 receptors (AT1) in the hypothalamic paraventricular nucleus (PVN) are located primarily in corticotropin releasing hormone (CRH) neurons of the parvicellular subdivision. The purpose of these studies was to investigate the role of AII regulating the hypothalamic-pituitary adrenal (HPA) axis, by correlating AT1 receptor expression levels in the PVN with the known changes in activity of the HPA axis under different stress paradigms, and manipulation of circulating glucocorticoids. AT1 receptor mRNA was measured by in situ hybridization using 35S-labelled cRNA probes and AII binding by autoradiography using 125I[Sar1,Ile8]AII in slide mounted hypothalamic sections. AT1 receptor mRNA levels and AII binding in the PVN were reduced by about 20% 18 h after adrenalectomy remaining at these levels up to 6 days after. This effect was prevented by corticosterone administration in the drinking water, or dexamethasone injection (100 mg, s.c., daily). Conversely, dexamethasone injection in intact rats caused a 20% increase in AT1 receptor mRNA in the PVN. AT1 receptor mRNA and binding in the PVN increased 4 h after exposure to stress paradigms associated with activation of the HPA axis (immobilization for 1 h, or i.p. injection of 1.5 M NaCl), and remained elevated after repeated daily stress for 14 days. Unexpectedly, two osmotic stress models associated with inhibition of the HPA axis (60 h water deprivation or 12 days of 2% saline intake) also resulted in increased AT1 receptor mRNA levels and AII binding in the parvicellular PVN. In intact rats, the stimulatory effect of acute stress on AT1 receptor mRNA in the PVN was significantly enhanced by dexamethasone administration (100 micrograms, s.c., 14 h and 1 h prior to stress), while in adrenalectomized rats, with or without glucocorticoid replacement, stress reduced rather than increased, AT1 receptor mRNA. Dexamethasone, 100 micrograms, injected sc within 1 min the beginning of immobilization in adrenalectomized rats, increased AT1 receptor mRNA in the PVN to levels significantly higher than those after dexamethasone alone, indicating that the stress induced glucocorticoid surge is required for the stimulatory effect of stress on AT1 receptor mRNA. The data suggest that AT1 receptor expression in the PVN is under dual control during stress: stress-activated inhibitory pathways and the stimulatory effect of glucocorticoids. The lack of specificity of the changes in AT1 receptor expression in the PVN following stressors with opposite effects on ACTH secretion (osmotic and physical-psychological stress) does not support a role for AII as a major determinant of the response of the HPA axis during stress.

Adrenalectomy↗

Subsequent malignancies in children and adolescents after treatment for Hodgkin's disease.

PURPOSE: We assessed the cumulative risk of malignancies following treatment for Hodgkin's disease in childhood and adolescence and investigated related patient and treatment characteristics. PATIENTS AND METHODS: Medical records of 499 Hodgkin's disease patients treated between 1962 and 1993 were reviewed. There were 385 adolescents (> or = 10 years of age at diagnosis) and 114 preadolescents (< 10 years). Most patients (n = 346) were treated with radiation plus multiagent chemotherapy, while 30 received only chemotherapy and 123 only radiation therapy. Radiation doses ranged from 20 to 42 Gy. RESULTS: At a median follow-up duration of 9 years (range, 0.1 to 27.4), 25 patients have had second malignancies: 19 solid tumors, four acute nonlymphoblastic leukemias (ANLLs), 1 non-Hodgkin's lymphoma (NHL), and one chronic myeloid leukemia (CML). Three patients have had a third malignancy. The estimated cumulative risk of second malignancies increased from 1.5% at 5 years to 7.7% at 15 years. All but two of the patients with second malignancies were > or = 10 years of age at initial diagnosis, which reflects the higher risk among patients treated for Hodgkin's disease as adolescents (P = .01). Second malignancies were more common among female patients (P = .0002), even when those breast cancer were excluded (P = .007), and in those treated for recurrent Hodgkin's disease (P = .02). Patients with ANLL/NHL were older at diagnosis of Hodgkin's disease than those with solid tumors, (median age, 18.3 v 13.8 years; P = .04). There was no difference between groups treated with radiation therapy alone, chemotherapy alone, or radiation plus multiagent chemotherapy. CONCLUSION: Adolescents treated for Hodgkin's disease are at greater at risk of second malignancies than younger patients. Overall, adolescent females treated for recurrent Hodgkin's disease appear to be at greatest risk, while preadolescents appear to be protected from this late complication.

Adolescent↗

Regulation of hypothalamic and pituitary corticotropin-releasing hormone receptor messenger ribonucleic acid by adrenalectomy and glucocorticoids.

The effects of adrenalectomy and glucocorticoids on the regulation of corticotropin-releasing hormone (CRH) receptor expression in the hypothalamic paraventricular nucleus (PVN) and pituitary were studied by in situ hybridization in the rat using a complementary RNA probe directed toward the coding region of the type 1 CRH receptor. Eighteen hours after adrenalectomy, CRH receptor messenger RNA (mRNA) expression in the PVN was significantly increased, whereas longer term adrenalectomy (4 and 6 days) had no effect. This transient effect of adrenalectomy was prevented by glucocorticoid replacement. In intact rats, 4 h after immobilization for 1 h or a single ip hypertonic saline injection, CRH receptor mRNA in the PVN markedly increased (P < 0.01), an effect that was unchanged by adrenalectomy (4 or 6 days) or dexamethasone injection (100 micrograms at -14 and 50 micrograms at -1 h) before stress. In the pituitary, CRH receptor mRNA levels decreased transiently after adrenalectomy (-62% after 18 h), returning to basal levels 4 or 6 days after adrenalectomy. The early decrease was prevented by glucocorticoid replacement. In intact rats, dexamethasone (100 micrograms, sc) caused a significant decrease in pituitary CRH receptor mRNA levels 2-10 h after injection, returning to basal levels after 15 h. On the other hand, dexamethasone (5-300 micrograms, sc) had no effect on pituitary CRH receptor mRNA levels 18 h after injection. The data show that although stress stimulation of CRH mRNA in the PVN is glucocorticoid independent, basal levels are likely to be under dual, transcriptional and posttranscriptional, control by glucocorticoids. In the pituitary, changes in hypothalamic CRFs probably play a major role in the control of CRH receptor mRNA levels during manipulations of circulating glucocorticoids levels. In addition, the inability of long term adrenalectomy and glucocorticoid administration to modify pituitary CRH receptor mRNA levels suggests that CRH receptor down-regulation observed under these experimental conditions depends mainly on translational and post-translational events rather than receptor mRNA levels.

Adrenalectomy↗

The nuclear receptor steroidogenic factor 1 is essential for the formation of the ventromedial hypothalamic nucleus.

The nuclear receptor steroidogenic factor 1 (SF-1) regulates the biosynthesis of the two essential mediators of male sexual differentiation, androgens and Müllerian-inhibiting substance, and is required for adrenal and gonadal development and gonadotropin expression. SF-1 is also expressed in the embryonic ventral diencephalon, subsequently localizing to the ventromedial hypothalamic nucleus, a region important for reproductive behavior. Mice lacking SF-1 secondary to targeted disruption of the Ftz-F1 gene had normal numbers and location of GnRH neurons but exhibited grossly impaired ventromedial hypothalamic nucleus structure. Despite their apparently normal GnRH neurons, treatment of Ftz-F1-disrupted mice with GnRH restored pituitary gonadotropin expression. These studies define SF-1's essential role within a discrete hypothalamic nucleus previously linked to reproduction.

Animals↗

Steroidogenic factor 1 is the essential transcript of the mouse Ftz-F1 gene.

Targeted disruption of the mouse Ftz-F1 gene, which encodes the orphan nuclear receptors steroidogenic factor 1 (SF-1) and embryonal long terminal repeat-binding protein (ELP), established that this gene is essential for development of the primary steroidogenic tissues and for male sexual differentiation. Associated with these dramatic developmental abnormalities, all Ftz-F1-disrupted mice died in the immediate postnatal period and had very low glucocorticoid levels. In this report, we show that treatment with corticosteroids markedly prolonged survival of the Ftz-F1-disrupted mice, proving that steroid hormone deficiency causes their death. We also generated SF-1-specific knockout mice with a targeting construct that specifically disrupted the SF-1 coding sequence without impairing the ELP protein. The phenotype of the SF-1-specific knockout mice was indistinguishable from that observed in Ftz-F1-disrupted mice that lack both SF-1 and ELP. Taken together, these results indicate that SF-1 is the Ftz-F1-encoded protein that is required for multiple aspects of endocrine development and for postnatal survival.

Adrenal Cortex Hormones↗

[Preconcentration of trace chromium in natural water with activated carbon and its determination by colorimetry].

The adsorption and desorption behavior of chromium was studied. Trace chromium in water could be adsorbed on activated carbon at pH 9-10, then eluted with 0.5% sulfuric acid and determined by colorimetry. The content of chromium could be concentrated by 100 times. For sample, the coefficient of variation of 8 parallel determinations was 7.7%. The proposed method has been applied to the determination of trace chromium in natural waters with the recovery of 71.4%-90.0%, and with the detection limit of 0.04 microgram/L.

Carbon↗

[Expression of desmoplakin II in tumors].

Desmoplakin II (DPII) is a new marker for identification of epithelium and epithelial tumors. Expression of DPII in 217 tumors cases was studied immunohistochemically by ABC method using an anti-DPII monoclonal antibody which reacts with tissue on formalin-fixed, paraffin-embedded sections. A monoclonal antibody against cytokeratin (CK) was employed to compare with the antibody. Immunohistochemical staining showed that 147 of the 163 epithelial tumors and bi-directional differentiation tumors expressed DPII (90.7%); 92 of the 163 tumors expressed CK (56.4%); 54 tumors lacking desmosome expressed neither DPII nor CK. All CK positive staining was located in cytoplasm while most DPII positive dotty staining was located at the cell-cell borders, some DPII staining was present in cytoplasm. These results demonstrate that the anti-DPII monoclonal antibody is a useful immunohistochemical probe for identification of desmosome-containing tumors. Antibodies against other epithelial markers such as keratin should be employed together with anti-DPII monoclonal antibody when differentiation is made between epithelial and non-epithelial tumors.

Adenocarcinoma↗

[The effect of qing guang kang on the metabolism of retinal ganglionic cells in rats after artificial acute high intraocular pressure].

A modified cytochrome oxidase (CO) histochemical and computer image techniques were used to examine the effect of Qing Guang Kang (QGK) injection on the metabolism of rat retinas after artificial acute high intraocular pressure. The results show that 75% of the average arterial blood pressure as the perfusing pressure of the anterior chamber of rats can lead to the decrease of numbers of CO active retinal ganglionic cells and their grey values. QGK possess the protective and/or improving effects on the CO active retinal ganglionic cells of rat under artificial acute high intraocular pressure. In the study, the data of density and the grey value of CO active ganglionic cells in the experimental models with QGK injection are significantly different from those of the control group (P < 0.05).

Animals↗

Quantitative analysis of (l)-ephedrine and (d)-pseudoephedrine in plasma by high-performance liquid chromatography with fluorescence detection.

Quantitative analysis of (l)-ephedrine (l-Ep) and (d)-pseudoephedrine (d-Ps) in plasma by high-performance liquid chromatography (HPLC) is described. The newly developed method is based on a precolumn derivatization with 5-dimethyl-aminonaphthalene-1-sulfonyl chloride (DNSC1) in acetonitrile. The diastereomers formed were separated on a reversed phase column by HPLC with fluorescence detection employing 0.6% phosphate buffer (pH 6.5)-methanol (3:8, v/v) as mobile phase. The detection limit of each Ephedra alkaloid stereoisomer was 0.5 ng at a signal-to-noise ratio of 3:1, the linear response to each stereoisomer being 1-800 ng.ml-1. The plasma level profile of l-Ep and d-Ps in guinea pig was investigated by this method. The determination of l-Ep and d-Ps in plasma of a volunteer after oral administration of Xiao Qinglong Heji was also performed.

Animals↗

[HPLC method for determination of lorcainide hydrochloride in human serum].

An analytical method was established for determination of lorcainide hydrochloride concentration in serum using high performance liquid chromatography (HPLC). The stainless steel column was 200 mm x 5.0 mm ID, packed with YWG C18H37, 5 microns. The mobile phase consisted of methanol-water-0.625 mol.L-1 ammonium acetate. (86:13:1 v/v), adjusted to the pH 8.0 with ammonium hydroxide. The flow rate was 1 ml.min-1, using diltiazem as internal standard. Chromatography was performed with ultraviolet detector at 226 nm. The recoveries of lorcainide hydrochloride at 40, 200 and 400 micrograms.L-1 were 95.85%, 100.63% and 100.09%, respectively. The within-day and day-to-day RSD of the determinations at concentrations of 100, 200, 400 and 800 micrograms.L-1 were less than 7%. Linear calibration curve for lorcainide hydrochloride was measured within the range of 20 to 800 micrograms.L-1 with correlation coefficient of 0.9996. The detection limit was 5 micrograms.L-1 in serum. The HPLC method described is suitable for clinical monitoring and pharmacokinetic study of lorcainide hydrochloride.

Adult↗

[Clinical research of muscular relaxation induced by alcuronium and pancuronium].

The clinical experiment was designed for observing effect of muscular relaxation induced by alcuronium and pancuronium. 40 patients were randomly divided into alcuronium group (A) and Pancuronium group (P). A group and P group were redivided into A1,A2 groups and P1,P2 groups according to differences of the initial doses of muscle relaxants. The results of neuromuscular monitoring indicate that onset time and main-tenance time of 0.3 mg/kg alcuronium were respectively 2.4 min and 63 min; 0.1 mg/kg pancuronium were 2.7 min and 70 min. The initial doses mentioned above are suitable to intubation of anesthesia and meet surgical need for muscular relaxation. The changes of MAP,HR,blood kalium and natrium were not evident in statistical significance before and after administration of relaxants.

Alcuronium↗

[Comparative study on hepatic and intestinal pathological changes in different animals with schistosomiasis japonica].

The pathological changes of livers and intestines were compared among cats, dogs and rabbits infected with Schistosoma japonicum cercariae for three months. The resuults showed that the most serious lesions were seen in rabbits while the slightest were in cats. The granulomatous response was more distinct in livers than in intestines in all the three animals. The increment ratio of egg granuloma in livers was 3.52, 2.64 and 1.81 in rabbits, dogs and cats, respectively. The eggs were deposited singly or in strings, few granuloma formation was observed in the intestines. In addition to inflammatory infiltration, swelling and/or dropping of mucosa the gland destruction and ulcer were also observed in the mucosa. The investigation demonstrated that pathological lesions varied in different animal species.

Animals↗

TGF beta and bFGF synthesis and localization in Dupuytren's disease (nodular palmar fibromatosis) relative to cellular activity, myofibroblast phenotype and oncofetal variants of fibronectin.

Nodular palmar fibromatosis is a self-limited proliferation of fibro-/myofibroblasts associated with growth factor synthesis and abundant fibronectin extracellular matrix deposition. bFGF and TGF beta are potent modulators of fibro-/myofibroblast proliferation and differentiation. Moreover, in vitro investigations evidenced a TGF beta 1-dependent regulation of alternative splicing of fibronectin mRNA. To investigate a possible implication of these growth factors in the tissue formation process of palmar fibromatosis, TGF beta 1/2 and bFGF synthesis, as well as TGF beta 1/3 and bFGF tissue distribution, is demonstrated by RNA in situ hybridization and/or immunohistochemistry in relation to myofibroblast phenotype development (alpha-smooth muscle actin, desmin immunohistochemistry), expression of different fibronectin isoforms (ED-A+, ED-B+ and oncofetal glycosylated fibronectin immunohistochemistry, fibronectin RNA in situ hybridization) and cellular activity (cyclin RNA in situ hybridization, Ki-67 immunolabelling). The myofibroblast phenotype (alpha-smooth muscle actin, desmin), the growth factor synthesis (TGF beta 1 and 2, bFGF), fibronectin matrix synthesis (RNA in situ hybridization with cDNA) and ED-A+, ED-B+ and oncofetal glycosylated fibronectin immunostaining are exclusively localized in the active proliferative nodules (Ki-67 immunolabelling and cyclin mRNA demonstration). Whereas the growth factor synthesis is restricted to the proliferative areas of the fibromatosis only, TGF beta 1, TGF beta 3 and bFGF proteins can also be detected immunohistochemically with a lower intensity in the surrounding aponeurotic tissue. The spatial correlation of myofibroblast phenotype, TGF beta and bFGF synthesis and the occurrence of the oncofetal molecular fibronectin variants (ED-B+ and oncofetal glycosylated fibronectin) in the active proliferative fibromatosis nodules suggests a pathogentic role of these growth factors and matrix components in the tumorous tissue formation process. The presence of the bFGF and TGF beta 1/3 proteins in fibroblasts neighbouring the proliferative nodules may point to a recruitment of quiescent aponeurotic fibroblasts in the fibromatous tissue formation process.

DNA, Complementary↗

The nuclear receptor steroidogenic factor 1 acts at multiple levels of the reproductive axis.

Steroidogenic factor 1 (SF-1), an orphan nuclear receptor, regulates the enzymes that produce sex steroids, and disruption of the Ftz-F1 gene encoding SF-1 precludes adrenal and gonadal development. We now study the role of SF-1 at other levels of the hypothalamic/pituitary/gonadal axis. In Ftz-F1-disrupted mice, immunohistochemical analyses with antibodies against pituitary trophic hormones showed a selective loss of gonadotrope-specific markers, supporting the role of SF-1 in gonadotrope function. In situ hybridization analyses confirmed these results; pituitaries from Ftz-F1-disrupted mice lacked transcripts for three gonadotrope-specific markers (LH beta, FSH beta, and the receptor for gonadotropin-releasing hormone), whereas they exhibited decreased but detectable expression of the alpha-subunit of glycoprotein hormones. SF-1 transcripts in the developing mouse pituitary, which first became detectable at embryonic day 13.5-14.5, preceded the appearance of FSH beta and LH beta transcripts. In adult rat pituitary cells, SF-1 transcripts colocalized with immunoreactivity for the gonadotrope-specific LH. Finally, SF-1 interacted with a previously defined promoter element in the glycoprotein hormone alpha-subunit gene, providing a possible mechanism for the impaired gonadotropin expression in Ftz-F1-disrupted mice. These studies establish novel roles of this orphan nuclear receptor in reproductive function.

Animals↗

Archaic structure of the gene encoding transcription factor USF.

The upstream stimulatory factor (USF) is a helix-loop-helix transcription factor that interacts with specific sites on the DNA that are also recognized by the MYC oncoproteins. We isolated genomic clones to the murine 44-kDa form of USF (USF2 gene). This unique gene spans 13 kilobases of DNA and is composed of 10 exons. The gene seems to have maintained its archaic structure, since many of the exons encode discrete functional domains of the transcription factor originally identified by protein sequence comparisons. A particularly striking HpaII tiny fragment island, extending over nearly 2,000 base pairs, surrounds the USF2 translation initiation site. This region, which includes the USF2 promoter and the first four exons, is characterized by an overall GC content greater than 74%. Analysis by S1 mapping and transient transfection assays revealed that the USF2 transcripts originate from an initiator element located within a highly GC-rich region that is surrounded by two long polyadenylate stretches and functions as a bidirectional promoter. Different forms of USF2 messages result from the presence or absence of the fourth exon in the processed USF2 mRNA. Alternative splicing correlates with the lack of a consensus lariat branch point in the third intron. Transient cotransfection assays revealed that the presence or absence of the amino acid sequences encoded by exon 4 affects considerably the transcription activation properties of the USF2 protein.

Alternative Splicing↗

Complete hematologic remissions induced by 2-chlorodeoxyadenosine in children with newly diagnosed acute myeloid leukemia.

The majority of children with acute myeloid leukemia (AML) who are treated exclusively with chemotherapy die of progressive disease. Improvement in outcome will likely require new active drugs capable of eradicating resistant blast cells early in the clinical course. We therefore assessed the cytoreductive potential of 2-chlorodeoxyadenosine (2-CdA), a halogenated purine analogue, in 22 consecutive children with newly diagnosed AML. The drug was administered as a single 120-hour continuous infusion (8.9 mg/m2 of body surface area per day) before the introduction of standard remission induction therapy. Six patients (27%) had complete hematologic remissions by a median of 21 days after treatment with the nucleoside (range, 14 to 33 days). Seven others had partial responses, yielding a total response rate of 59%. The drug also eliminated leukemic cells from cerebrospinal fluid in 4 of the 6 patients tested. Concentrations of 2-CdA in cerebrospinal fluid on day 5 after the initiation of treatment ranged from 12.4% to 38.0% (mean, 22.7%) of the steady-state plasma concentrations. Severe but reversible myelosuppression and thrombocytopenia developed in all patients. Analysis of factors that may have influenced the complete remission rate suggested a better outcome in patients with myeloblastic leukemia (M0-M2 subtypes in the revised French-American-British classification system). These results demonstrate clinically significant activity by 2-CdA against previously untreated AML in children, including leukemic blast cells in the central nervous system. Its use in combination chemotherapy may improve the outlook for patients with this often fatal hematologic cancer.

Adolescent↗

A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation.

Studies in adrenocortical cells have implicated the orphan nuclear receptor SF-1 in the gene regulation of the steroid hydroxylases. We used targeted disruption of the Ftz-F1 gene, which encodes SF-1, to examine its role in intact mice. Despite normal survival in utero, all Ftz-F1 null animals died by postnatal day 8; these animals lacked adrenal glands and gonads and were severely deficient in corticosterone, supporting adrenocortical insufficiency as the probable cause of death. Male and female Ftz-F1 null mice had female internal genitalia, despite complete gonadal agenesis. These studies establish that the Ftz-F1 gene is essential for sexual differentiation and formation of the primary steroidogenic tissues.

Adrenal Glands↗