Biomedical subjects

X Jiang

Publications and source records attributed to X Jiang.

At least 415 records · Page 23Linked to original sources

PubMed1994

Changes in gene expression of AMPA-selective glutamate receptor subunits induced by status epilepticus in rat brain.

In the present investigation we address the question of whether one of the responses to increased neuronal activity is a modification of the expression of the different subunits of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-selective glutamate receptors (GluR-1, GluR-2, GluR-3). Thus, we used two different models of generalized status epilepticus, as widespread elevated neuronal activity, to study in vivo responses of the AMPA receptor mRNA expression in rat forebrain. By Northern blot analysis and in situ hybridization, we show that one of the delayed responses to LiCl/pilocarpine-induced status epilepticus is a dramatic change in the mRNA level of some subunits of AMPA-selective glutamate receptors. These effects, which appear between 6 and 12 h after the drug treatment, are subunit and brain region specific. The most striking example of differential expression of the three examined GluR mRNAs can be observed in the dentate gyrus of the hippocampus. In this specific brain subregion an increase of GluR-3 mRNA level is induced 12 h after LiCl/pilocarpine treatment, while a clear decrease in GluR-1 mRNA level and no significant change in GluR-2 mRNA level can be observed in the same area under these experimental conditions. Both the GluR-1 decrease and the GluR-3 increase are transient effects and a return to basal level can be observed after 48-72 h. In the CA1 layer of the hippocampus, a parallel decrease of both GluR-1 and GluR-3 expression is found 12-24 h after drug treatment, followed by a recovery of the expression to control values at 48 h. In kainate-induced epilepsy we could reproduce the late increase (12-24 h) in GluR-3 mRNA in the dentate gyrus; however, under this experimental condition, no clear decrease of GluR-1 expression can be observed in this area. A general decrease in mRNA level for the AMPA receptor subunits (GluR-1-3) in the hippocampal layers, in particular in CA3 and CA4 subfields, was also observed. In conclusion the results reported in the present paper reveal a specific regulation of GluR gene expression in the granule cells of the hippocampal dentate gyrus and stimulate further investigation on the functional role of the GluR-3 subunit in the receptor-channel complex.

Animals↗

PubMed1994

Tilted amides in amino acid and peptide derivatives.

BACKGROUND: Amide bonds in peptides and proteins typically adopt planar cis or trans conformations. Conversions between cis and trans amide conformations are necessary for protein folding and for many other processes, but are difficult to achieve since they involve disruption of the planarity of the bond. As a first step to understanding cis-trans isomerization, we set out to synthesize and characterize peptides that mimic the tilted or twisted amide structures that are postulated to form the intermediate states in this process. RESULTS: We have synthesized a model amino acid and four dipeptide derivatives containing a methyl-substituted aziridine residue. Single crystals of phenacyl (2R, 3R)-benzyloxycarbonyl-3-methyl-2-aziridinecarboxylate and phenacyl (2R, 3R)-acetyl-glycyl-3-methyl-2-aziridine-carboxylate were obtained. Using X-ray diffraction analysis, we determined that the amide nitrogens of the aziridine rings have tetrahedral sp3-like geometry with tilt angles in the range of 37-38 degrees. The 13C-NMR spectra indicate that the amide carbonyl is dramatically shifted downfield as a consequence of the tilt. CONCLUSIONS: In peptides containing a substituted aziridine ring, the orbitals of the amide nitrogen are constrained into a tilted configuration. These peptides may mimic the transition state between cis and trans amide conformations. This technique thus provides a novel strategy for the study of isomerization and other biorecognition processes.

Amides↗

PubMed1994

Microalbuminuria in young adults related to blood pressure in a biracial (black-white) population. The Bogalusa Heart Study.

The association between microalbuminuria and blood pressure levels was examined in young white and black adults (n = 1131) aged 19 to 32 years. Urinary ratio of albumin (mg/L) to creatinine (mmol/L) was used as an estimation of urinary albumin excretion. Black men and women compared with their white counterparts had higher levels of blood pressure. Significantly positive correlations between urinary albumin excretion and systolic and diastolic blood pressures were observed in black men (r = 0.20 and r = 0.24, P < .01) and black women (r = 0.15 and r = 0.14, P < .05). Similar correlations of significance were not seen in the white counterparts. Systolic and diastolic blood pressure levels were significantly higher in normotensive black subjects (< 140/90 mm Hg) with increased urinary albumin excretion (> or = 90th percentile) than in those without increased urinary albumin excretion. After accounting for potential confounding by age, sex, and body mass index, blacks in the uppermost systolic and diastolic blood pressure group were 7.1 times (95% CI, 2.0 to 25.8) and 4.8 times (1.3 to 18.3), respectively, as likely to have elevated albumin/creatinine excretion as those in the lowest group. In contrast, the likelihood for elevated albumin/creatinine excretion were 0.9 times (95% CI, 0.5 to 2.2) and 1.1 times (0.5 to 2.3), respectively, in whites, which were not significant. These data suggest that a stronger association between blood pressure levels and urinary albumin excretion exists in young blacks than in whites, which supports the notion that blacks may be more susceptible to renal damage from relatively low levels of blood pressure increases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Detection of Norwalk virus or Norwalk-like virus infections in Finnish infants and young children.

Norwalk virus (NV) and Norwalk-like viruses are important causes of epidemic nonbacterial gastroenteritis in older children and adults. Serologic responses to NV of 154 Finnish infants and young children participating in a rotavirus vaccine study were examined by ELISA with a recently available baculovirus-expressed recombinant NV capsid protein. In 4 serially collected sera (at the median ages of 3, 4, 14, and 23 months), 49% of children had at least one NV infection over the approximately 2-year study period. Children with low NV-specific IgG titers (< 1:50) at the median age of 4 or 14 months were significantly more likely to acquire an NV infection by the median age of 14 or 23 months, respectively, than children who had higher NV IgG titers (> 1:50) (P < .05). Thus, NV or Norwalk-like virus infections are more common in infants and young children than previously believed, and antibody to NV may be protective against such infections.

Caliciviridae Infections↗

PubMed1994

Norwalk virus infection of volunteers: new insights based on improved assays.

Norwalk virus infection is a common cause of gastroenteritis in humans. The clinical features and virologic and immunologic responses following oral administration of Norwalk virus to 50 volunteers were monitored. New ELISAs using recombinant virus particles as the antigen source were used to assess the pattern of virus shedding and the specific immune responses. Forty-one subjects (82%) became infected; 68% were symptomatic and 32% were asymptomatic. The proportion of subjects infected was similar for those with and without preexisting antibody (82% vs. 60%; P > .2). The magnitude of seroconversion was highest in subjects who had vomiting. The peak of viral shedding was between 25 and 72 h, and virus first appeared in stool at 15 h. Specimens collected 7 days after inoculation remained positive. These results show a higher infection rate, more subclinical infections, and longer virus excretion following Norwalk virus inoculation than previously recognized.

Adult↗

PubMed1994

Epidemiological study of Norwalk virus infections in Japan and Southeast Asia by enzyme-linked immunosorbent assays with Norwalk virus capsid protein produced by the baculovirus expression system.

In this study, we investigated Norwalk virus (NV) antigen and antibody to recombinant NV (rNV) in human populations in Japan and Southeast Asia by enzyme-linked immunosorbent assays (ELISAs). Baculovirus-expressed recombinant NV (rNV) capsid protein was used for preparing antisera to rNV or used as an antigen for detecting antibody to rNV. The ELISAs were specific for NV and had sensitivities equivalent to or higher than those of the previously developed radioimmunoassays. In 159 stool samples obtained from children, mainly younger than 10 years old, with acute gastroenteritis due to small round structured viruses in Japan, only 1 was positive for NV antigen. The pattern of acquisition of antibody to rNV was quite different from those of antibodies to group A rotavirus and human calicivirus Sapporo (HuCV-Sa) strain. The prevalence of antibody to rNV remained at a low level throughout childhood and then showed a steep rise during school age and early adulthood in Japan. A high prevalence of antibody was observed in samples collected from healthy adults in Japan and Southeast Asia. These results suggested that NV infection is common in adults in Japan and Southeast Asia but may be rare in infants in Japan. The HuCV-Sa strain was negative by the ELISA, and no serological relationship between NV and the HuCV-Sa strain was found. NV may be quite different from the HuCV-Sa strain, although both viruses are classified in the family Caliciviridae.

Adolescent↗

PubMed1994

Norwalk virus-associated gastroenteritis traced to ice consumption aboard a cruise ship in Hawaii: comparison and application of molecular method-based assays.

Investigation of an outbreak of acute nonbacterial gastroenteritis on a cruise ship provided an opportunity to assess new molecular method-based diagnostic methods for Norwalk virus (NV) and the antibody response to NV infection. The outbreak began within 36 h of embarkation and affected 30% of 672 passengers and crew. No single meal, seating, or food item was implicated in the transmission of NV, but a passenger's risk of illness was associated with the amount of ice (but not water) consumed (chi-square for trend, P = 0.009). Of 19 fecal specimens examined, 7 were found to contain 27-nm NV-like particles by electron microscopy and 16 were positive by PCR with very sensitive NV-specific primers, but only 5 were positive by a new highly specific antigen enzyme immunoassay for NV. Ten of 12 serum specimen pairs demonstrated a fourfold or greater rise in antibody titer to recombinant baculovirus-expressed NV antigen. The amplified PCR band shared only 81% nucleotide sequence homology with the reference NV strain, which may explain the lack of utility of the fecal specimen enzyme immunoassay. This report, the first to document the use of these molecular method-based assays for investigation of an outbreak, demonstrates the importance of highly sensitive viral diagnostics such as PCR and serodiagnosis for the epidemiologic investigation of NV gastroenteritis.

Antibodies, Viral↗

PubMed1994

Application of PCR to detect Norwalk virus in fecal specimens from outbreaks of gastroenteritis.

Norwalk virus (NV) and other small round-structured viruses (SRSVs) are frequent causes of gastroenteritis outbreaks. The recent cloning and sequencing of the NV genome has made it possible to detect NV and Norwalk-related viruses from fecal specimens by reverse transcription (RT)-PCR. We applied this technique to the examination of a total of 139 fecal specimens from 19 outbreaks characterized by NV serology, including 56 samples from 7 NV outbreaks, 36 from 6 Norwalk-related virus outbreaks, and 47 from 6 outbreaks with SRSVs visualized by electron microscopy that were serologically unrelated to NV. Three primer pairs were evaluated: two pairs in the polymerase region of NV and one pair near the 3' end of the genome. When one set of primers (primer pair 51-3) from the polymerase region was used, 40% of all samples were positive by RT-PCR and specimens from the NV outbreaks were more likely to be positive (64%) than those from outbreaks associated with Norwalk-related viruses (44%) or SRSVs (8%). To determine the relationship of the outbreak strains to NV, we compared the sequences of a 145-base portion of the polymerase gene from 10 specimens obtained from five different outbreaks characterized as NV by serology. No two outbreak strains had the same sequence in this 145-base portion of the polymerase gene, and the identities of the nucleotide and amino acid sequences of these products compared with the sequences of the corresponding region of NV ranged from 62 to 79% and 69 to 90%, respectively. Because of sequence diversity in the polymerase region, the successful application of RT-PCR to investigations of outbreaks of suspected NV-associated gastroenteritis will depend on the use of either multiple primer pairs or primers made against regions of the genome that are more conserved.

Amino Acid Sequence↗

PubMed1994

Identification of minireovirus as a Norwalk-like virus in pediatric patients with gastroenteritis.

In 1977, 30- to 32-nm virus-like particles, named minireovirus because of their unique morphologic appearance, were detected by electron microscopy in the stools of infants and young children with gastroenteritis. Sequence analysis of approximately 2,800 consecutive bases derived from overlapping PCR clones of a recent minireovirus clinical isolate showed 52% nucleotide sequence identity with the Norwalk virus sequence and, in addition, demonstrated that the genomic organizations of these two viruses were similar. Our data show that minireovirus is a Norwalk-like virus and should now also be included in the Caliciviridae family.

Amino Acid Sequence↗

PubMed1994

Three-dimensional structure of baculovirus-expressed Norwalk virus capsids.

The three-dimensional structure of the baculovirus-expressed Norwalk virus capsid has been determined to a resolution of 2.2 nm using electron cryomicroscopy and computer image processing techniques. The empty capsid, 38.0 nm in diameter, exhibits T = 3 icosahedral symmetry and is composed of 90 dimers of the capsid protein. The striking features of the capsid structure are arch-like capsomeres, at the local and strict 2-fold axes, formed by dimers of the capsid protein and large hollows at the icosahedral 5- and 3-fold axes. Despite its distinctive architecture, the Norwalk virus capsid has several similarities with the structures of T = 3 single-stranded RNA (ssRNA) viruses. The structure of the protein subunit appears to be modular with three distinct domains: the distal globular domain (P2) that appears bilobed, a central stem domain (P1), and a lower shell domain (S). The distal domains of the 2-fold related subunits interact with each other to form the top of the arch. The lower domains of the adjacent subunits associate tightly to form a continuous shell between the radii of 11.0 and 15.0 nm. No significant mass density is observed below the radius of 11.0 mm. It is suspected that the hinge peptide in the adjoining region between the central domain and the shell domain may facilitate the subunits adapting to various quasi-equivalent environments. Architectural similarities between the Norwalk virus capsid and the other ssRNA viruses have suggested a possible domain organization along the primary sequence of the Norwalk virus capsid protein. It is suggested that the N-terminal 250 residues constitute the lower shell domain (S) with an eight-strand beta-barrel structure and that the C-terminal residues beyond 250 constitute the protruding (P1+P2) domains. A lack of an N-terminal basic region and the ability of the Norwalk virus capsid protein to form empty T = 3 shells suggest that the assembly pathway and the RNA packing mechanisms may be different from those proposed for tomato bushy stunt virus and southern bean mosaic virus but similar to that in tymoviruses and comoviruses.

Baculoviridae↗

PubMed1994

Sequence diversity of small, round-structured viruses in the Norwalk virus group.

We have determined the nucleotide sequences of a highly conserved region of the RNA-dependent RNA polymerase of the prototype Snow Mountain agent (SMA) and of four other small, round-structured viruses (antigenically Norwalk virus [NV]-like or SMA-like) following reverse transcription-PCR amplification of viral RNA obtained from human stools. The stool samples were either from volunteers administered SMA or from sporadic cases and outbreaks of gastroenteritis that occurred in Japan and the United Kingdom between 1984 and 1992. The GLPSG and YGDD RNA polymerase motifs were in the proper locations in the sequences of the five SRSVs, but each sequence was distinct from the 8FIIa prototype NV sequence and from each other. Analysis of the sequences and reactivities in a new NV antigen enzyme-linked immunosorbent assay showed that the five viruses could be divided into two groups (serogroups) with NV and SMA, respectively, being the prototypes. The sequences of the capsid region and a nonstructural region (2C) were determined from one strain from each group. One virus (SRSV-KY-89/89/J), isolated in Japan and antigenically similar to the prototype NV (isolated 21 years earlier in Ohio), showed a remarkable level of sequence similarity to NV. KY-89 and the 8FIIa NV showed 87.2% nucleotide similarity over 2,516 continuous nucleotides amounting to 96 to 98.9% amino acid similarity in three distinct domains in two open reading frames. Between the prototype SMA and NV, the polymerase region showed 63% nucleotide and 59% amino acid similarity, respectively. Two other antigenically SMA-like isolates (SRSV-925/92/UK and SRSV-OTH-25/89/J), from the United Kingdom and Japan, showed 80% nucleotide and 88 to 92% amino acid similarity in the polymerase region to the prototype SMA isolated 16 and 13 years earlier in the United States. The capsid region of the antigenically SMA-like OTH-25 virus showed 53% nucleotide and 65% amino acid similarity to the prototype NV capsid region. Domains of sequence diversity and conversation were identified within the capsid protein of these two distinct prototype serotypes of virus. These results indicate that NV-like and SMA-like agents are still circulating, and sequence comparisons will be useful to identify and classify distinct viruses in the NV group.

Base Sequence↗

PubMed1994

Ventilatory responses to hypoxia in rats pretreated with nonpeptide NK1 receptor antagonist CP-96,345.

This study reports experiments designed to evaluate the role of neurokinin-1 (NK1) receptors for substance P (SP) in the ventilatory response to acute hypoxia. Ventilation was measured by indirect plethysmography in eight unanesthetized unrestrained adult rats before and after bolus injection of 1, 5, or 10 mg/kg (ip) of CP-96,345 (Pfizer), a potent nonpeptide competitive antagonist of the SP NK1 receptor. Ventilation was measured while the rats breathed air or 8% O2-92% N2 with and without administration of SP antagonist. Pretreatment with CP-96,345 decreased the magnitude of the hypoxic response in a dose-dependent fashion. Minute ventilation in rats pretreated with CP-96,345 was reduced by 22.1% (P < 0.05) at the highest dose (10 mg/kg), largely because of an attenuation of the frequency component. Although both control and treated rats responded to hypoxia with a decrease in duration of inspiration and expiration rats pretreated with CP-96,345 displayed a smaller decrease in inspiration and expiration than control rats (P < 0.05). We have recently shown that neuropeptide-containing fibers are important for mediating the tachypnic response during acute isocapnic hypoxia in rats. The attenuation in minute ventilation at the highest dose (10 mg/kg) is comparable in magnitude to the attenuation observed with neonatal capsaicin treatment, which permanently ablates neuropeptide-containing unmyelinated fibers. Accordingly, this previously reported role of capsaicin-sensitive nerves in the hypoxic ventilatory response of rats is probably attributable to released SP acting at NK1 receptors. One of the likely sites of action of SP antagonists is the carotid body.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

[The observation of the bulbar conjunctival microcirculation in patients with retinitis pigmentosa].

The detection of the bulbar conjunctival microcirculation (BCM) of 73 cases (146 eyes) with retinitis pigmentosa (RP) showed that there were some abnormal changes of BCM in the pathologic progress of RP. The older the patient, the longer the disease history and the more the loss of visual field, the more serious the abnormal changes of BCM. The disease in male patients was in general more serious than in female patients. Its characteristics were the followings: increase in the number of tortuous vessels; the different widths of vessels in a few cases; obvious increase of microangioma; abnormal proportion of artery to vein; decelerated blood flow and aggregated erythrocytes. Some abnormal changes in the nailfold microcirculation (left ring finger) were observed in the meantime, and compared with those in the BCM of 56 cases. It was found that they were positively interrelated (gamma's = 0.9965, P < 0.001).

Adolescent↗

PubMed1994

Preliminary report of molecular detection of retinoblastoma gene mutations.

To develop gene diagnosis for retinoblastoma predisposition, it is necessary to disclose the retinoblastoma gene mutations or deletions in detail. Genomic DNA from tumor and peripheral white blood cells in 33 patients with retinoblastoma was detected with 3.8kb probe derived from 3' end of retinoblastoma gene cDNA. The gene abnormalities, including deletion, partial deletion and rearrangement, were found in 18 patients. Further research will be aimed at microdeletions or mutations for those patients without detectable variations in Southern hybridization.

Blotting, Southern↗

PubMed1994

[Analysis on refraction status of eyes with normal vision].

Refractive status of 1,324 eyes with normal vision of the juvenile students in four grades was analysed. It was raised that the meaning of refractive status was different between the medical physiological optics and the physical or geometrical optics. "Emmetropia" did not really mean "the normal eye" in refraction as viewed from normal physiology, and the problem about the physiological refractive status of eyes in the juvenile was discussed preliminarily.

Adolescent↗

PubMed1994

Epidemiology of early primary hypertension and implications for prevention: the Bogalusa Heart Study.

Epidemiological studies of BPs in children and young adults over the past 20 years have contributed considerably to understanding the early onset of primary hypertension. Observations from autopsies and echocardiographic studies, together with long-term BP studies, of children clearly indicate that primary hypertension begins in early childhood. Although abnormal BP levels in children are much lower than the adult criteria used for clinical diagnosis of hypertension, essential hypertension is identifiable in early life. Complex haemodynamic and metabolic mechanisms related to essential hypertension are also being identified in childhood. The development of intervention programs in an attempt to prevent hypertension in its early phases suggests hypertensive cardiovascular disease is preventable. Environmental factors (improved dietary factors, altering electrolyte intake, prevention of obesity and increased activity levels) are critical elements to prevention. Children and young adults identified as high risk for hypertension need to be targeted for prevention of early cardiovascular renal disease. Also, as hypertension is so prevalent, attempts should be made to control environmental factors in the general public. Preventive programmes established by primary healthcare physicians, paediatricians and para-professionals can have a major impact on the reduction of hypertension and its complications of cardiovascular renal disease in the future.

Adolescent↗

PubMed1993

Macrophage control of Brucella abortus: role of reactive oxygen intermediates and nitric oxide.

Macrophages infected with Brucella abortus are able to kill intracellular brucellae over the first 12 to 24 hr following infection. Thereafter, the surviving brucellae replicate. We have shown previously that macrophages activated with interferon-gamma (IFN-gamma) have enhanced brucellacidal and brucellastatic activities. In studies reported here, treatment of macrophages with methylene blue, an electron carrier, enhanced the initial killing of intracellular brucellae, indicating their susceptibility to reactive oxygen intermediates. In addition, inhibitors of reactive oxygen intermediates partially blocked the antibrucella activities exhibited by both non-cytokine-treated and IFN-gamma-activated macrophages. In contrast, addition of up to 5 mM NG-monomethyl-L-arginine, to block generation of nitric oxide, resulted in minor but significant levels of blocking of macrophage antibrucella activities only when macrophages were not maximally activated even though maximally activated macrophages produced nitric oxide as indicated by accumulation of nitrite in culture supernatants. In addition, while the J774A.1 macrophage cell line had antibrucella activities which were enhanced by IFN-gamma activation, it did not produce nitric oxide when activated with IFN-gamma and infected with B. abortus. Finally, the IFN-gamma-induced enhancement of antibrucella activities by peritoneal macrophages was inhibited by addition of antitumor necrosis factor-alpha (TNF-alpha) antibodies to the cultures, indicating that TNF-alpha is necessary for full expression of the macrophage antibrucella activities.

Animals↗

PubMed1993

Persistent activation of the zeta isoform of protein kinase C in the maintenance of long-term potentiation.

Long-term potentiation in the CA1 region of the hippocampus, a model for memory formation in the brain, is divided into two phases. A transient process (induction) is initiated, which then generates a persistent mechanism (maintenance) for enhancing synaptic strength. Protein kinase C (PKC), a gene family of multiple isozymes, may play a role in both induction and maintenance. In region CA1 from rat hippocampal slices, most of the isozymes of PKC translocated to the particulate fraction 15 sec after a tetanus. The increase of PKC in the particulate fraction did not persist into the maintenance phase of long-term potentiation. In contrast, a constitutively active kinase, PKM, a form specific to a single isozyme (zeta), increased in the cytosol during the maintenance phase. The transition from translocation of PKC to formation of PKM may help to explain the molecular mechanisms of induction and maintenance of long-term potentiation.

Amino Acid Sequence↗