Search PubMed⌕ Search

Biomedical subjects

J Xie

Publications and source records attributed to J Xie.

At least 181 records · Page 10Linked to original sources
PubMed1997

High-energy defibrillation increases the severity of postresuscitation myocardial dysfunction.

BACKGROUND: The fatal outcome of victims after initially successful resuscitation from cardiac arrest has been attributed both to global myocardial ischemia during the interval of cardiac arrest and to the adverse effects of reperfusion. The present study was prompted by earlier experimental observation that the magnitude of myocardial dysfunction was in part related to the energy delivered during electrical defibrillation. METHODS AND RESULTS: Ventricular fibrillation (VF) was induced in 15 Sprague-Dawley rats. Precordial compression was begun together with mechanical ventilation after 4 minutes of untreated VF and continued for 6 minutes. Spontaneous circulation was restored in each animal after external defibrillation with a single stored 2-, 10-, or 20-J countershock. Cardiac index and the rate of left ventricular pressure rise at left ventricular pressure of 40 mm Hg (dP/dt40) and fall (negative dP/dt) during the 240-minute interval after successful resuscitation were decreased, and left ventricular diastolic pressure was increased. These decreases in myocardial function were closely related to the energy of electrical defibrillation. After a 20-J shock, animals survived for only 5+/-3 hours; after a 10-J shock, animals survived for 15+/-4 hours; and after a 2-J shock, all animals survived for >24 hours. CONCLUSIONS: The severity of postresuscitation myocardial dysfunction is related, at least in part, to the magnitude of the electrical energy of the delivered shock.

Animals↗
PubMed1997

Mutations of the PATCHED gene in several types of sporadic extracutaneous tumors.

Patients with basal cell nevus syndrome have a high incidence of multiple basal cell carcinomas, medulloblastomas, and meningiomas. Because somatic PATCHED (PTCH) mutations have been found in sporadic basal cell carcinomas, we have screened for PTCH mutations in several types of sporadic extracutaneous tumors. We found that 2 of 14 sporadic medulloblastomas bear somatic nonsense mutations in one copy of the gene and also deletion of the other copy. In addition, we identified missense mutations in PTCH in two of seven breast carcinomas, one of nine meningiomas, and one colon cancer cell line. No PTCH gene mutations were detected in 10 primary colon carcinomas and eighteen bladder carcinomas.

Amino Acid Sequence↗
PubMed1997

MNDA dimerizes through a complex motif involving an N-terminal basic region.

Human myeloid cell nuclear differentiation antigen (MNDA) is a myelomonocytic lineage-specific protein that influences gene expression through interactions with other nuclear proteins and transcription factors. MNDA also self-associates and chemical cross-linking was used to demonstrate that MNDA forms a dimer. C-terminal and internal deletion mutants were used to identify two regions in the N-terminal half of MNDA essential for self-association. One region contains an imperfect leucine zipper and the second is highly enriched in basic residues. The sequences that are essential for dimerization are separated by a highly basic amphipathic alpha-helical region which was not required for dimerization.

Amino Acid Sequence↗
PubMed1997

Buspirone, a 5-hydroxytryptamine1A agonist, is active in cerebellar ataxia. Results of a double-blind drug placebo study in patients with cerebellar cortical atrophy.

OBJECTIVE: To establish the antiataxic effect of buspirone hydrochloride, a serotonergic 5-hydroxytryptamine1A (5-HT1A) agonist, in a homogenous group of patients characterized by the same well-defined single condition, cerebellar cortical atrophy. SETTING: University ataxia research center. METHODS: Double-blind randomized study of buspirone vs placebo during a 4-month period. PATIENTS: Nineteen patients met the inclusion criteria; all completed the study. Of these 19 patients, 9 were treated with placebo and 10 were treated with the drug. MAIN OUTCOME MEASURES: A semiquantitative scale for kinetic and static ("postural") cerebellar functions; quantitative clinical measurements measuring time in standard tests that evaluated stance, speech, writing, and drawing; and posturographic analysis of the sway path and sway area of the center-of-foot pressure. The primary end point was improvement of the posttherapeutic change of one of the semiquantitative ataxic scores. The secondary end points were modification of the changes of quantitative measures--clinical or posturographic. RESULTS: In intention-to-treat analysis, a significant improvement of the primary end point, ie, the posttherapeutic change of the ataxic kinetic score, was shown. Among secondary end points, the maximum time of standing with feet together also was significantly improved. CONCLUSIONS: Buspirone is active in cerebellar ataxia of patients with cerebellar atrophy. These results confirm the data suggested by open-label studies with buspirone. However, the effect is partial and not clinically major. These pharmacological results might be due to serotonergic mechanisms and confirm a possible link between cerebellar ataxia and the metabolism of serotonin.

Adult↗
PubMed1997

Mutation analysis of the gonadotropin-releasing hormone receptor gene in idiopathic hypogonadotropic hypogonadism.

OBJECTIVE: To determine if GnRH receptor mutations occur in patients with idiopathic hypogonadotropic hypogonadism. DESIGN: Patients and controls were studied by molecular genetic analysis. SETTING: A tertiary medical center setting. PATIENT(S): Twenty-four patients with idiopathic hypogonadotropic hypogonadism and 20 controls. INTERVENTION(S): Deoxyribonucleic acid from all individuals was analyzed by Southern blot analysis and denaturing gradient gel electrophoresis. Genomic DNA was digested with restriction enzymes, and Southern blots and denaturing gradient gel blots were constructed. Blots were hybridized with the GnRH receptor complementary DNA probe. The DNA sequencing was performed on samples from two representative patients. MAIN OUTCOME MEASURE(S): Gonadotropin-releasing hormone receptor gene structure was ascertained by comparing fragments from autoradiographs in patients and controls. Individual nucleotides were ascertained from DNA sequencing gels. RESULT(S): No GnRH receptor gene deletions or polymorphisms were identified by Southern blot analysis. New restriction-fragment melting polymorphisms using the enzymes DpnII, RsaI, and HaeIII were identified by denaturing gradient gel blots in patients and controls. CONCLUSION(S): Gonadotropin-releasing hormone receptor gene deletions or rearrangements were not observed in our idiopathic hypogonadotropic hypogonadism patients. Denaturing gradient gel electrophoresis failed to identify single-base differences unique to patients with idiopathic hypogonadotropic hypogonadism, dramatically reducing the likelihood that point mutations of the GnRH receptor gene are present in idiopathic hypogonadotropic hypogonadism.

Adolescent↗
PubMed1997

Buspirone, a serotonergic 5-HT1A agonist, is active in cerebellar ataxia. A new fact in favor of the serotonergic theory of ataxia.

We have previously proposed a serotonergic hypothesis for cerebellar ataxia and mentioned that the levorotatory form of 5-hydroxytryptophan, a serotonin precursor, is partially active in subtypes of cerebellar ataxia, including cerebellar cortical atrophy (CCA). It has been demonstrated that 5-HT1A serotonergic receptors play an important role in the control of Purkinje cells discharges and in the inhibition of the release of glutamate by cerebellar glutamatergic terminals. To test further the serotonergic hypothesis of cerebellar ataxia, we administered buspirone, a 5-HT1A agonist usable in human medicine, in a randomized double blind drug placebo trial for 4 months. Nineteen patients with CCA were included; nine patients were given placebo and 10 Buspirone, at the mean dose of 0.69 mg/kg. The evaluation of ataxia was based on a static and a kinetic ataxia scale, fully quantitative measures and the evaluation of the sway path and area at posturography. At 4 months, a significant effect of buspirone was observed for drug induced gains of the kinetic score, two items of the static score, and the maximum duration of standing upright with feet together. These results indicate that a novel chemical therapeutic approach is possible for cerebellar ataxia; moreover, they support the existence of a link between cerebellar ataxia and disturbances of the serotonergic cerebellar system, especially a serotonergic deficit.

Anxiety↗
PubMed1997

Cingulate cortex synaptic terminal proteins and neural cell adhesion molecule in schizophrenia.

The neuronal organization and patterns of afferent innervation are abnormal in the cingulate cortex in schizophrenia, and associated changes in synaptic terminals could be present. A panel of monoclonal antibodies was defined with biochemical and fusion protein studies as detecting syntaxin (antibody SP6), synaptophysin (antibody SP4) and synaptosomal-associated protein-25 (antibody SP12). These antibodies and a polyclonal antibody reactive with neural cell adhesion molecule were used to investigate the cingulate cortex in schizophrenia. Immunocytochemistry indicated that syntaxin immunoreactivity had a considerably wider distribution than synaptophysin. Overall, multivariate analysis indicated increased synaptic terminal protein immunoreactivity in schizophrenia compared to controls (P=0.004). Controlled for age and post mortem interval, syntaxin immunoreactivity was significantly elevated in schizophrenia (P=0.004), and neural cell adhesion molecule immunoreactivity was also elevated (P=0.05). The neural cell adhesion molecule to synaptophysin ratio was increased (P=0.005), possibly indicating the presence of less mature synapses in schizophrenia. Elevated syntaxin immunoreactivity is consistent with increased glutamatergic afferents to the cingulate cortex in schizophrenia, and combined with the neural cell adhesion molecule to synaptophysin ratio results suggests that synaptic function in this region in schizophrenia may be abnormal.

Antigens↗
PubMed1997

Modulation of RNase H activity by modified DNA probes: major groove vs minor groove effects.

We have previously prepared ribozyme mimics and chemical nucleases from modified DNA containing pendant bipyridine and terpyridine groups. The ability of these modified DNA probes to support RNase H cleavage of complementary RNA is described. DNA/RNA duplexes were formed using DNA probes designed to deliver metal complexes via either the major groove or the minor groove of the duplex. The duplexes were treated with Escherichia coli RNase H. Modifications in the major groove produced the same RNA cleavage pattern as unmodified DNA probes. However, minor groove substituents inhibited RNA cleavage over a four-base region. Comparison was made with a DNA probe containing a 2'-OMe modification. Our results support enzyme binding in the minor groove of a DNA/RNA duplex. We do not observe cleavage directly across from the modified nucleoside. The RNA cleavage efficiency effected by RNase H and a DNA probe decreases as follows: unmodified DNA > or = C-5 modified DNA >> c2'-modified DNA > C1'-modified DNA. Results with 28-mer RNA substrates roughly parallel those obtained with a 159-mer RNA target. The differences observed between low and high MW RNA substrates can be explained by a much higher enzyme-substrate binding constant for the high MW target.

Base Sequence↗
PubMed1997

Adverse effects of interrupting precordial compression during cardiopulmonary resuscitation.

OBJECTIVES: In the current operation of automated external defibrillators, substantial time may be consumed for a "hands off" interval during which precordial compression is discontinued to allow for automated rhythm analyses before delivery of the electric countershock. The effects of such a pause on the outcomes of cardiopulmonary resuscitation were investigated. DESIGN: Prospective, randomized, controlled animal study. SETTING: Research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Ventricular fibrillation was electrically induced in 25 Sprague-Dawley rats. After 4 mins of untreated ventricular fibrillation, precordial compression was begun and continued for 6 mins. Animals were then randomized to receive an immediate defibrillation shock or the defibrillation attempt was delayed for intervals of 10, 20, 30, or 40 secs. MEASUREMENTS AND MAIN RESULTS: Immediate defibrillation restored spontaneous circulation in each instance. When defibrillation was delayed for 10 or 20 secs, spontaneous circulation was restored in three of five animals in each group. After a 30-sec delay, spontaneous circulation was restored in only one of five animals (p < .05). No animal was successfully resuscitated after a 40-sec delay (p < .01). With increasing delays, 24- and 48-hr survival rates were correspondingly reduced. CONCLUSIONS: During resuscitation from ventricular fibrillation, prolongation of the interval between discontinuation of precordial compression and delivery of the first electric countershock substantially compromises the success of cardiac resuscitation. Accordingly, automated defibrillators are likely to be maximally effective if they are programmed to secure minimal "hands off" delay before delivery of the electric countershock.

Animals↗
PubMed1997

Dissociation of TNF-alpha from endotoxin-induced nitric oxide and acute-phase hypotension.

We tested the concept that tumor necrosis factor-alpha (TNF-alpha) or platelet-activating factor (PAF) mediated Escherichia coli endotoxin lipopolysaccharide (LPS)-induced upregulation of nitric oxide (NO) and acute-phase hypotension (APH) in the rat. LPS (0.5 mg/kg i.v.) given to rats treated with saline or nonimmune goat-derived gamma-globulin (immunoglobulin G, 22 mg/kg i.m.) produced APH and increased plasma concentrations of TNF-alpha and nitrate and nitrite anions (reactive nitrogen intermediates; RNI) and NO in ex vivo incubates of polymorphonuclear neutrophils (PMN) and inducible NO synthase (iNOS) mRNA in PMN. Pretreatment of rats with a polyclonal TNF-alpha antibody (TNF-Ab, 22 mg/kg i.m.) abolished LPS-mediated increases in plasma TNF-alpha but failed to inhibit APH or the NO system. TNF-alpha (8.2 micrograms/kg i.v.) produced transient hypertension and sustained tachycardia and increased plasma TNF-alpha and PMN iNOS mRNA but not RNI. LPS and TNF-alpha decreased spontaneous and calcimycin (Ca2+ ionophore, 1 microM)- and PAF (1 microM)-mediated increases in head-space NO production by rings of mesenteric artery incubated ex vivo. TNF-Ab abolished all effects of TNF-alpha. PAF (25, 50, and 100 ng/kg) produced APH without increasing plasma TNF-alpha, RNI, or PMN iNOS mRNA. The PAF receptor antagonist BN-50730 (80 micrograms/kg i.v.) abolished PAF-induced APH and attenuated LPS-induced increases in RNI. We conclude that 1) LPS produces parallel but unrelated changes in TNF-alpha and RNI in plasma and PMN during the APH of endotoxemia; and 2) endogenous TNF-alpha is not required for LPS-mediated induction of iNOS mRNA, and PAF mediates LPS-induced APH.

Animals↗
PubMed1997

Effects of NO synthase inhibitors, arginine-deficient diet, and amiloride in pregnant rats.

This study tests the hypothesis that nitric oxide synthase (NOS) inhibition is linked to NG-nitro-L-arginine methyl ester (L-NAME)-mediated intrauterine growth retardation (IUGR) and fetal limb reduction deficits (LRD) in pregnant dams. Administration of L-NAME (1 mg/ml) or aminoguanidine (AG, 500 micrograms/ml) in the drinking water or intraperitoneal administration of L-N5-(1-iminoethyl)-ornithine (L-NIO, 10 mg.kg-1.day-1) on gestational days 13-20 decreased nitrite and nitrate plus nitrate (RNI) levels in the urine and plasma and decreased RNI in incubates of aorta and fetal limbs compared with pregnant rats given amiloride (50 micrograms/ml) or water (control). Although all drugs caused fetal IUGR, only L-NAME and amiloride caused fetal deaths and LRD. Urine and tissue levels of RNI were unchanged in rats fed and arginine-free diet (AFD) on gestational days 13-20, and yet fetal IUGR, deaths, and LRD were prevalent. L-NAME potentiated the fetal abnormalities and resorptions. Plasma arginine concentrations decreased with AFD > > L-NAME > L-NIO. Plasma ornithine, a precursor for polyamine synthesis, decreased with AFD and increased with L-NAME. Thus inhibition of NOS is not linked to LRD. The ability of L-NAME and amiloride to produce fetal IUGR and LRD may result from L-NAME-mediated modulation of amino acid delivery to the fetus and amiloride-mediated inhibition of protein synthesis. Finally, IUGR appears unrelated to LRD.

Abnormalities, Drug-Induced↗
PubMed1997

Esophageal PCO2 as a monitor of perfusion failure during hemorrhagic shock.

Measurement of gastric wall PCO2 (PgCO2) by tonometric method has emerged as an attractive option for estimating visceral perfusion during circulatory shock. However, gastric acid secretion obfuscates the tonometric measurement. We, therefore, investigated the option of measuring PCO2 in the esophagus to minimize these restraints. Hemorrhagic shock was induced in five Sprague-Dawley rats, and five rats served as sham controls. PgCO2 was measured with an ion-sensitive field effect transistor that was surgically implanted into the gastric wall. Esophageal luminal PCO2 (PeCO2) was measured by a second ion-sensitive field effect transistor sensor. During hemorrhagic shock, mean aortic pressure declined from 150 to 50 mmHg. Gastric blood flow decreased from 58 to 12 ml.min-1.100 g-1 (21% of preshock) and esophageal blood flow from 44 to 7 ml.min-1.100 g-1 (16% of preshock). PgCO2 simultaneously increased from 47 to 116 Torr and PeCO2 from 47 to 127 Torr. The increases in PgCO2 were highly correlated with increases in PeCO2 (r = 0.90). Esophageal tonometry may, therefore, serve as a practical alternative to gastric tonometry.

Animals↗
PubMed1997

Extracellular matrix regulates ovarian hormone-dependent proliferation of mouse mammary epithelial cells.

Mammary stromal cells can modulate steroid hormone responsiveness both in vivo and in vitro. One of the mechanisms by which stromal cells can influence epithelial cell behavior is by modifying the composition of the extracellular matrix (ECM). In this report, we have investigated the effects of five ECM molecules on control of epithelial cell proliferation by estrogen (E2) and progestin (R5020) under serum-free culture conditions. To assess the contribution of mammary gland differentiation in determining epithelial cell interactions with ECM, the behavior of mammary epithelial cells derived from nulliparous and pregnant mice was compared. We report the novel finding that the proliferative responses of mammary epithelial cells to progestin is influenced by specific ECM molecules. However, the primary determinant of hormonal responsiveness is the developmental state of the gland from which the epithelial cells were derived. Nulliparous-derived epithelial cells, proliferated in response to R5020 only on fibronectin (FN) and collagen IV (Col IV). The more highly differentiated, pregnancy-derived epithelial cells were not responsive to E2 or R5020 on any ECM. To determine if steroid hormone receptors were targets of ECM-mediated effects, ER and PR levels were analyzed. In both nulliparous and pregnancy-derived cultures, PR binding levels were maintained at similar levels on all ECMs. However, ER levels were not maintained in nulliparous-derived cultures, and this may have contributed to the lack of a significant response to E2. Alternatively or in addition, E2-induced responses may require additional signals or growth factors that are provided by stromal cells in vivo or by serum supplementation in vitro. These results demonstrate the ECM molecules, fibronectin and collagen IV, can modulate responsiveness of mammary epithelial cells to R5020 in vitro, and may be the mediators of stromal influences on hormone responsiveness in vivo. However, the specific effects of ECM and hormones are also determined by the developmental state of the mammary gland from which the cells are derived. Thus, mammary gland differentiation, ovarian hormones, and ECM composition may act in concert to determine the outcome of hormone treatment on cell proliferation.

Animals↗
PubMed1997

Resistance to thyrotropin (TSH) in three families is not associated with mutations in the TSH receptor or TSH.

Resistance to TSH (RTSH) is a recently described syndrome of reduced sensitivity to TSH that manifests as euthyroid hyperthyrotropinemia. It is usually identified at birth during routine neonatal screening for congenital hypothyroidism. In less than 2 yr, 13 subjects with RTSH belonging to 8 families have been reported, and all were shown to harbor mutations in the TSH receptor (TSHR) gene. We now report the occurrence of RTSH in 3 unrelated families. Contrary to previous reports, the inheritance of RTSH in 2 of the families was dominant rather than recessive and was not associated with abnormalities in the TSHR gene. Abnormalities in the TSHR gene were excluded by sequencing all coding sequences, exon/intron junctions, and the promoter region of the gene. Furthermore, the involvement of the TSHR in the manifestation of the RTSH phenotype was excluded in 2 families by linkage analysis using intragenic polymorphic markers. We excluded defects in the TSH beta-subunit by sequencing its gene and by showing that the circulating TSH in affected subjects from all families had normal bioactivity. Also, no abnormalities were found in the Gs alpha gene of one family analyzed by GC-clamped denaturing gradient gel electrophoresis. This study shows that RTSH may be a manifestation of several different genetic defects that requires the exploration of other candidate genes involved in the TSH-TSHR-Gs alpha cascade and genes participating in its regulation.

Adult↗
PubMed1997

[Ventriculo-peritoneal shunts for thirty-two patients with traumatic hydrocephalus].

Thirty-two patients with traumatic hydrocephalus were treated by ventriculo-peritoneal shunts. Twenty-two patients were improved (70%). Among them, seventeen patients showed satisfactory results (53%): ventriculo-peritoneal shunts have good effects and few complications; this method is easy to manipulate for traumatic hydrocephalus. We discussed the important points in operations.

Adolescent↗
PubMed1997

[Taxonomic studies of two Streptomycete strains AS 4.693 and AS 4.702].

The "setae group" of the genus Streptomyces was originally the genus Kitasatosporia (Omura, 1982). On the basis of 16s rRNA analysis, Wellington(1992) proposed to reduce Kitasatosporia to synonymy with Streptomyces as a species group--"setae group". Two Streptomyces strains, AS 4.693 and AS 4.702(deposited in CCCCM) were examined by using morphological, chemical and nucleic acid ribtyping methods. It was revealed that these two strains have similarity to the type strain Streptomyces setae JCM3304T, and they share 100% DNA homology with JCM 3304T. Therefore, we propose that the strain AS 4.693 be transferred to the "setae group" of genus Streptomyces as Streptomyces setae subsp. irregularis nov. and the strain AS 4.702 as Streptomyces setae subsp. flexuofradiae nov.

DNA, Bacterial↗
PubMed1997

[Cloning and expression of the E. coli serine hydroxymethyltransferase gene (glyA)].

The E. coli K12 glyA gene(13 kb), encoding serine hydroxymethyltransferase (SHMT), has been cloned in the plasmid vector pBR329 using insertion inactivation and complementation test. Subcloning of segments of the original insert (13 kb) into plasmids pBR322, pBR329 and pSMY901 established that a 2.6 kb PstI-EcoR fragment carries the glyA gene. The 12 strains of transforments containing recombined plasmid. were obtained. SHMT and glyA gene product level in strains carrying glyA plasmids were different. No SHMT activity was observed in host strains. The glyA gene products for JM109(pSM13), K12(pSM13), K12(pSM14) and K12(pSM15) account for 15.7%, 15.4%, 11.8%, and 9.48% of the total dissoluble cell protein, respectively.

Cloning, Molecular↗