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Biomedical subjects

X Sun

Publications and source records attributed to X Sun.

At least 487 records · Page 27Linked to original sources

Presence of apolipoprotein E on extracellular neurofibrillary tangles and on meningeal blood vessels precedes the Alzheimer beta-amyloid deposition.

The localization of apolipoprotein E (ApoE) has been examined immunohistochemically in the autopsied brains of middle-aged and old-aged control subjects, with and without amyloid beta protein (A beta) deposits, and of Alzheimer's disease patients. Senile plaques were consistently labeled with ApoE antiserum even in the very early stage of senile plaque formation seen in the fifth decade. In the cerebellar molecular layer, small dots of ApoE immunoreactivity, which were prominent in the Alzheimer's disease subjects, were observed in addition to immunoreactivity in diffuse plaques. ApoE antisera labeled all of the extracellular neurofibrillary tangles (NFT), whereas only a small minority of extracellular NFT were positive for A beta. A punctate pattern of ApoE immunoreactivity was seen at the media of the meningeal vessels lacking amyloid, when senile plaques were present in the nearby cortex. In the early stage of amyloid angiopathy, the distribution of ApoE immunoreactivity was much more extensive than that of A beta positivity. These findings suggest that ApoE accumulates in the early stage of senile plaque formation and, furthermore, that ApoE accumulation precedes A beta deposition in extracellular NFT and amyloid angiopathy.

Aged↗

Reduced cerebellar blood flow and oxygen metabolism in spinocerebellar degeneration: a combined PET and MRI study.

Fourteen patients with spinocerebellar degeneration (SCD) were subjected to MRI and PET studies. The quantitative MRI data revealed significant cerebellar and pontine atrophy in the patients with olivopontocerebellar atrophy (OPCA), and cerebellar atrophy in the patients with late cerebellar cortical atrophy (LCCA). We failed to demonstrate significant differences in the pons between LCCA patients and normal controls. PET measurements revealed decreases in cerebral oxygen metabolic rate (CMRO2) in the cerebellar hemisphere and vermis in both groups of patients. The markedly decreased cerebral blood flow (CBF) and CMRO2 in the pons were found only in the patients with OPCA. PET data corrected for the tissue shrinkage on the basis of MRI morphometry indicated a net reduction in cerebellar CMRO2 and CBF. The present study has demonstrated that a combination of functional and anatomical data offers further evidence in favour of the current acceptable classification of SCD based on clinicopathological grounds. Our data further suggest that the amount of atrophy in the cerebellum could not fully account for the decreased metabolic rates observed in PET studies.

Adult↗

Modulation of wingless signaling by Notch in Drosophila.

Extensive genetic and molecular analyses indicate that Notch acts as a transmembrane receptor in an evolutionarily conserved cell interaction mechanism that appears to control a common step in the progression of an uncommitted cell towards the differentiated state. In Drosophila, Notch mutations were shown to affect the development of a broad spectrum of tissues, including the wing. We found that mutations in the segment polarity gene wingless are capable of acting as dominant enhancers of notchoid, a recessive Notch allele affecting the wing. The Wingless protein is homologous to the mammalian proto-oncoprotein Wnt-1 and is thought to act as the signal in a cell interaction mechanism that specifies differentiation of the embryonic epidermis as well as imaginal structures such as the wing. Although some components of the Wingless signal transduction pathway have been identified, the receptor for Wingless remains elusive. This genetic link between the Wingless and Notch pathways has been further examined by determining the relative expression patterns and subcellular localization of Notch and Wingless in mutant and wild-type backgrounds. We find that Notch is necessary for the implementation of the Wingless signal in specifying normal wing development. We discuss the possibility that Notch is directly involved in the reception of Wingless in the light of current models for the developmental action of Notch.

Animals↗

Steroidal saponins from Smilax menispermoidea and S. lebrunii.

Three new (25S)spirost-5-en-3 beta,17 alpha,27-triol glycosides were isolated from the rhizomes and roots of Smilax menispermoidea and S. lebrunii. Their structures were elucidated by means of spectroscopic and chemical methods. Several known saponins were also isolated and identified.

Carbohydrate Sequence↗

Albumin and transferrin synthesis are increased in H4 cells by serum from analbuminemic or nephrotic rats.

The hepatic synthesis of several proteins, including both albumin and transferrin is increased in the nephrotic syndrome. While active suppression of albumin synthesis by lymphokines has been described, it has been assumed that augmentation of albumin synthesis is governed by a physical factor, plasma oncotic pressure (pi), and that this regulation is by a direct effect of pi on hepatocytes. The mechanisms have not been defined. Furthermore, experiments relying on suppression of protein synthesis may only test non-specific inhibitory effects of the experimental intervention. We tested an alternative hypothesis that a serum factor(s) present in hypooncotic states stimulates albumin synthesis. We incubated an immortalized cell line derived from rat hepatocytes (H4 cells) with serum from Nagase analbuminemic rats (NAR) and rats with passive Heymann nephritis (HN), a model of the nephrotic syndrome. Synthesis (incorporation of [35S]methionine) into both albumin and transferrin was increased significantly. The stimulatory effect of these sera was not extinguished by addition of rat or human albumin to the medium prior to or during incubation, even when pi in the incubation medium was increased to normal plasma levels by added albumin. Incorporation of [35S]methionine into albumin was 7841 +/- 394 cpm/mg cell protein using 10% NAR serum in the presence of human albumin (medium pi 26.1 +/- 0.17) versus 5149 +/- 420 cpm incorporation (P < 0.05) in the presence of control serum and in the absence of added albumin (medium pi 2.06 +/- 0.26 mm Hg, P < 0.001). The stimulatory activity was preserved following heating of serum for one hour at 60 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Injecting drug use and HIV infection in southwest China.

OBJECTIVES: To determine the prevalence of drug injection among drug users, the seroprevalence of HIV and risk factors for HIV infection among injecting drug users (IDU), and to determine heterosexual transmission of HIV among IDU and their spouses in southwest China. METHODS: Using a cross-sectional design, we conducted an HIV seroprevalence and behavioral survey in three rural counties of Yunnan province, Ruili, Longchuan and Luxi in southwest China, bordering Myanmar (Burma). A total of 860 drug users were recruited in randomly selected communities at the three study sites (response rate, 97%). In addition, a random sample of 62 wives of HIV-infected IDU were assembled from 460 known HIV-positive IDU in Ruili and Longchuan (response rate, 81%). RESULTS: In the sample of 860 drug users, 33% reported injecting drugs. Among the 282 subjects who injected drugs, 82% began intravenous drug use after 1988; 64% injected drugs at least once every day. All subjects shared needles but none cleaned the injection equipment with alcohol or bleach. Overall, 49% tested HIV-positive. HIV seropositivity was independently correlated with a longer history of drug injecting, daily injecting, frequent needle-sharing, being younger, and living in Ruili county. Among the 62 wives of HIV-positive IDU, none used condoms during sex and 10% tested HIV-positive. CONCLUSIONS: We conclude that the introduction of HIV into drug-using communities and the rapid increase in heroin injecting in this population appear to have triggered an explosive HIV epidemic among IDU in southwest China. We recommend that AIDS prevention efforts should begin immediately and focus on discouraging the shift from opium smoking to heroin injecting, needle-sharing, and unprotected sex among drug users and their partners.

Adult↗

Histamine-independent modulation of the neuropeptide Y-induced pressor response by alpha-trinositol in the pithed rat.

The modulatory effects of alpha-trinositol (D-myo-inositol-1.2.6- trisphosphate; PP 56) on the systemic arterial blood pressor responses induced by neuropeptide Y, preganglionic nerve stimulation, phenylephrine and vasopressin were studied in pithed rats. Intravenous administration (within 2 min.) of alpha-trinositol reduced the neuropeptide Y-induced increase in mean arterial pressure within a defined dose range without altering the heart rate. The influence of alpha-trinositol on the neuropeptide Y-induced pressor response in the presence of non-selective as well as H1- and H2-selective histamine antagonists (diphenhydramine, mepyramine and cimetidine respectively) were investigated. The maximal increase in mean arterial pressure induced by neuropeptide Y as well as the duration of the pressor response was enhanced after nonselective (diphenhydramine) or H1-selective (mepyramine) histamine blockade. The enhancement of the neuropeptide Y-induced pressor response by the H1 specific antagonist mepyramine was significantly more pronounced compared to the H2-selective agent. The exaggerated increase in mean arterial pressure in response to neuropeptide Y after histamine blockade was inhibited by alpha-trinositol to a similar extent as without such pretreatment. We conclude that neuropeptide Y interacts with histamine in the pithed rat and that this action may partially offset the pressor actions of the peptide. The neuropeptide Y-induced pressor responses may be inhibited by alpha-trinositol within a defined dose range indicating that this non-peptide agent may act as a functional inhibitor to neuropeptide Y in vascular tissue.

Animals↗

Tumour necrosis factor and endotoxin synergistically activate intestinal phospholipase A2 in mice. Role of endogenous platelet activating factor and effect of exogenous platelet activating factor.

Previous studies have shown that: (a) platelet activating factor induces shock and intestinal injury, (b) exogenous platelet activating factor stimulates synthesis of endogenous platelet activating factor, and (c) tumour necrosis factor alpha and endotoxin synergise to induce shock and bowel injury in animals. These last two effects are largely mediated by platelet activating factor forming phospholipase A2 A2, a key enzyme for platelet activating factor synthesis, was examined in mouse intestine. It was found that tumour necrosis factor alpha and endotoxin synergise to stimulate platelet activating factor forming phospholipase A2 activity in the intestine, as well as platelet activating factor production, and these effects were blocked by pretreatment with platelet activating factor antagonists, SRI-63-441 and WEB 2086. In addition, exogenous platelet activating factor stimulates intestinal phospholipase A2 activity. These results show that tumour necrosis factor alpha and lipopolysaccharide synergistically activate the phospholipase A2 that participates in platelet activating factor formation, and this activation is largely mediated by endogenous platelet activating factor. Furthermore, platelet activating factor itself increases phospholipase A2 activity, suggesting that platelet activating factor induces its own synthesis, probably by phospholipase A2 activation.

Animals↗

Localization of Alzheimer amyloid beta protein precursor and its relation to senile plaque amyloid.

The authors examined the ultrastructural localization of amyloid beta protein precursor (APP) in normal human brains immunohistochemically using 3 kinds of APP antisera. The patterns of immunoreaction differed between the antisera used. Antiserum 770, against APP1-770, predominantly labeled the cytoplasm of neurons, whereas antiserum Z31, against the pre-beta region of the APP, labeled astroglial processes intensely and neurons to a lesser extent. Antiserum 1736, against the N terminal of beta protein, labeled both neurons and astrocytes. Vascular smooth muscle cells and some of the endothelial cells in the cerebral arterioles and capillaries were labeled with Z31 and 1736. The APP exists in every cells, while various patterns of immunoreactivity may reflect the difference in the metabolic pathway of APP between cell types.

Aged↗

Evaluation of definitions for adult respiratory distress syndrome.

We conducted a cohort study of 423 intensive care unit (ICU) admissions with a primary clinical diagnosis of acute respiratory failure, a PaO2/FIO2 on ICU admission of < 300 mm Hg, and an ICD-9 discharge diagnosis of adult respiratory distress syndrome (ARDS) (518.5 or 518.82) drawn from a nationally representative database of 17,440 ICU admissions to evaluate current and proposed revisions for definitions of ARDS. A variety of nonpulmonary physiologic risk factors, from shock to elevated serum bilirubin measurements, were significant (p < 0.01) for hospital mortality. Multivariable analysis using the admission APACHE III score, primary ICU admission diagnosis, and treatment location before ICU admission provided greater accuracy in prediction (ROC = 0.80) than the individual PaO2/FIO2 (ROC = 0.68). Patients were given an individual risk of hospital mortality based on their admission APACHE III score, treatment location before ICU admission, and ICU admitting diagnosis. Dividing the patient population into groups using a PaO2/FIO2 < or = 150 resulted in a wide range of individual risk for hospital mortality, from < 10 to > 90% in both groups. We conclude that ARDS is a complex clinical entity with a variety of pulmonary and nonpulmonary risk factors for both its development and its prognosis. Current and proposed categorical definitions based on the severity of hypoxemia result in a wide distribution of individual patient risks. Use of these findings in the design and conduct of future clinical trials would improve the evaluation of new therapies.

Adolescent↗

A new kind of fasciolicide: molecular and electronic structures of some o-hydroxybenzenesulfonanilides.

The molecular and electronic structures of some fasciolicidal o-hydroxybenzenesulfonanilides (HBSA) have been studied using X-ray diffraction and semiempirical MO calculation. In these compounds, the phenolic hydroxyl forms a strong intramolecular hydrogen bond with an adjacent sulfonyl oxygen atom and the strength of the d-p dative S<--N bond, which may control the electron delocalization throughout the entire molecule, is affected by substituents on the phenyl rings on both sides. Owing to the poor delocalization, the contribution of the keto-form of the resonance structure is larger for some phenolate anions of HBSA in solution, and this may be a key factor determining the potency of fasciolicidal activity of HBSA.

Anilides↗

Role of the NH2-terminus of substance P in the inhibition by capsaicin of behavioral sensitization to kainic acid-induced activity in the adult mouse.

Activation of primary afferent C-fibers by repeated intrathecal injection of kainic acid (KA) in mice is inhibited after pretreatment with capsaicin. The increased behavioral response to multiple injections of KA is thought to be brought about by an action of the NH2-terminus of substance P (SP). In light of our recent observation that the antinociceptive effect of capsaicin may also involve an action of the NH2-terminus of SP, we tested the hypothesis that capsaicin inhibits behavioral sensitization to KA by a desensitization to the action of the NH2-terminus of SP. Using adult mice, pretreatment (24 hr) with either capsaicin (0.8 micrograms) or SP(1-7) (1 and 10 nmol) attenuated sensitization of the behavioral response to four injections of 25 pmol of KA at 2-min intervals. Pretreatment with 10 nmol of the COOH-terminal SP fragment, SP(5-11), had no effect. [D-Pro2,D-Phe7]-SP(1-7), a SP NH2-terminal antagonist, injected 5 min before capsaicin or SP(1-7), inhibited the effects of both capsaicin and SP(1-7) on KA sensitization whereas the COOH-terminal neurokinin antagonist, [D-Pro2,D-Trp7,9]-SP, did not. The similarities in behavioral responses after treatment with SP(1-7) or capsaicin, together with the sensitivity of these effects to D-SP(1-7), suggest that SP released in response to capsaicin may inhibit subsequent KA-induced activity 24 hr later. This action of SP appears to be brought about by its NH2-terminus and/or an accumulation of its NH2-terminal metabolites after capsaicin treatment.

Amides↗

An antinociceptive effect of capsaicin in the adult mouse mediated by the NH2-terminus of substance P.

Capsaicin in the adult animal is believed to evoke a massive release of substance P (SP) and a subsequent loss of primary afferent C-fiber activity. Given the antinociceptive effect of SP N-terminal metabolites, the present experiments were designed to compare behavioral and nociceptive responses after treatments with capsaicin or the SP NH2-terminal fragment, SP(1-7), and to determine whether they share a common mechanism of action. When adult mice were tested using the hot-plate assay, 24 hr after intrathecal injections of either capsaicin (0.3-2.6 nmol) or SP(1-7) (22.5 pmol-10 nmol), a dose-related antinociception was observed. The caudally directed biting and scratching behaviors induced by 1 nmol of capsaicin injected intrathecally were also greatly reduced 24 hr after either 2.6 nmol of capsaicin or 10 nmol of SP(1-7). Pretreatment with an antagonist of the NH2-terminus of SP, [D-Pro2,D-Phe7]-SP(1-7), prevented the long-term effects of capsaicin and of SP(1-7) on capsaicin-induced behaviors in our paradigm at doses that the COOH-terminal antagonist of neurokinin activity, [D-Pro2,D-Trp7,9]-SP, did not. The antinociceptive effect of capsaicin in the adult animal is, therefore, mimicked by SP(1-7) and attenuated by [D-Pro2,D-Phe7]-SP(1-7), suggesting that the NH2-terminus of SP and its NH2-terminal metabolites, released in response to capsaicin, may contribute to the mediation of capsaicin's antinociceptive effect.

Analgesics↗

The NH2-terminus of substance P modulates NMDA-induced activity in the mouse spinal cord.

Excitatory amino acids (EAAs) and substance P are believed to transmit nociceptive information in the spinal cord. As substance P NH2-terminal fragments can modulate non-NMDA EAA-mediated activity, we examined the effects of substance P fragments to ascertain whether the COOH- or NH2-terminus of substance P modulates the actions of NMDA in the spinal cord. NMDA activity was measured by the intensity of behaviors produced by NMDA (0.2 nmol) administered intrathecally in the mouse. The NMDA response was attenuated after pretreatment with either substance P (22.5 pmol, 30 min) or the NH2-terminal fragment of substance P, SP-(1-7). Pretreatment with the COOH-terminal fragment SP-(5-11) (22.5 pmol, 30 min), a neurokinin ligand, had no effect on NMDA-induced behaviors, suggesting that the inhibitory effect of substance P is caused by the NH2-terminus. Pretreatment with D-Pro2,D-Phe7 substance P-(1-7), a SP-(1-7) antagonist, potentiated NMDA activity, suggesting a tonic inhibitory effect of the substance P NH2-terminus. Desensitization to NMDA typically develops when NMDA is injected at 2 min intervals. While pretreatment with SP-(1-7) inhibited NMDA, coadministration of SP-(1-7) (22.5 pmol), with the first of four injections of NMDA, first inhibited but then potentiated responses to each challenge with NMDA. Coadministration of the same dose of SP-(1-7) with the fourth injection of NMDA immediately potentiated the response to NMDA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Subcutaneous injection of fatty tissue pearls--experimental study and clinical applications].

In 20 female adult rats, fatty tissue of 0.6 or 1.2 g was taken from each side of the pelvis. One fatty block, after being cut into pearls of about 2 mm in diameter, was injected subcutaneously to the left side of the back while another was transplanted en bloc in the right side. The rats were randomized into four groups and samples of fat were taken at 3, 6, 12 and 24 weeks. After 24 weeks, the sample from left side was found to be 21.1% of its original weight while the right side was only 6.9% (P < 0.05). In clinical practice, subcutaneous fat was sucked out from submandibular or abdominal regions, cut into pearls of 2-3 mm in diameter and injected to depressed area, such as glabella or naso-labial grooves. The procedure was applied to 27 sites of 15 cases. Follow-up of 6 months showed satisfactory results in 51.9%, acceptable in 18.5% and no effect in 29.6%.

Adipose Tissue↗

Primary chronic angle-closure glaucoma in Chinese--a clinical exploration of its pathogenesis and natural course.

Forty-three cases (86 eyes) of primary chronic angle-closure glaucoma were randomly selected. An additional 44 cases (77 eyes) of primary acute angle-closure glaucoma and 30 normal subjects (34 eyes) were also randomly enrolled as control groups for comparison in the clinical study. Ultrasonic biometric measurements of the anterior chamber depth, lens thickness and axial length of the eyeball were performed. Using an potic microgauge attached to the slit-lamp, the entrance of anterior chamber angle was also calculated. The clinical manifestations and the natural course, including the characteristic appearance of anterior chamber angle, the form of peripheral anterior synechia as well as the facility of outflow, were carefully investigated. There were significant differences in the biometric parameters of the anterior segment of eye among above three groups. The facts reveal that the anatomic features of eyeball, especially in the anterior segment differentiate from those of primary acute angle-closure glaucoma. Follow-up study for the early stage cases showed that topical administration of miotics and/or peripheral iridectomy can effectively prevent iris from forming peripheral anterior synechia and thus halt its development. The criteria of diagnosis and the principles of prevention and treatment at the early stage cases were presented. The pathogenesis was discussed. We emphasized that the progressive stage after intermittent attacks of primary acute angle-closure glaucoma should not be confused with primary chronic angle-closure glaucoma.

Adult↗