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Biomedical subjects

D Zhou

Publications and source records attributed to D Zhou.

At least 253 records · Page 14Linked to original sources

Migration of dendritic cells in response to formyl peptides, C5a, and a distinct set of chemokines.

Trafficking to tissues and then to lymph nodes is a crucial aspect of the immunobiology of dendritic cells. The present study was designed to identify molecules able to direct the migration of human blood-derived dendritic cells. fMLP (representative of formyl peptides of bacterial origin), C5a, and the C-C chemokines monocyte chemotactic protein (MCP)-3, MIP-1 alpha/LD78, and RANTES elicited chemotactic migration and a rise of intracellular free calcium in dendritic cells. In contrast, the C-X-C chemokines IL-8 and IP-10 and the C-C chemokines MCP-1 and MCP-2 were inactive as chemoattractants. Thus, dendritic cells respond to classical chemotactic signals and to a set of chemokines distinct from that active on monocytes and neutrophils. Chemoattractants are likely to contribute to localization and trafficking of dendritic cells and provide tools to recruit these cells in the design of immunization strategies.

Calcium↗

Endotoxin receptors (CD14) are found with CD16 (Fc gamma RIII) in an intracellular compartment of neutrophils that contains alkaline phosphatase.

CD14 is a glycosylphosphatidylinositol (GPI)-anchored protein on the surfaces of monocytes and polymorphonuclear leukocytes (PMN) that binds and initiates cellular responses to bacterial LPS. PMN also contain an intracellular pool of CD14 that can be deployed rapidly to the cell surface in response to stimulation with a variety of agonists. To determine which of the well-characterized subcellular compartments of PMN contains CD14, cells were cavitated and fractionated on Percoll gradients. The gradient fractions were assayed for CD14 by ELISA and Western blot and for the marker proteins beta-glucuronidase (azurophil granules), vitamin B12 binding protein (specific granules), alkaline phosphatase (secretory vesicles and plasma membrane), and HLA (plasma membrane). Approximately one-half of the CD14 ran with plasma membrane fractions and one-half with intracellular membranes of light density. Both intracellular and cell surface CD14 were associated tightly with membrane, and both forms showed identical electrophoretic mobility. The intracellular CD14 was clearly not present in azurophil granules or specific granules, but ran precisely with alkaline phosphatase, a marker for secretory vesicles. Parallel studies showed that an additional GPI-linked protein, Fc gamma RIII (CD16), also fractionated precisely with CD14 and alkaline phosphatase. Association of CD14 with secretory vesicles were confirmed by studies on cells stimulated with the formyl peptide fNLLP for 20 min at 37 degrees C before fractionation. This treatment caused translocation of CD14 from intracellular fractions to plasma membrane fractions. No release of the specific granule marker vitamin B12 binding protein was observed under these conditions, whereas two other GPI-anchored proteins, alkaline phosphatase and CD16, moved coincidentally with CD14 to comigrate with the plasma membrane. Time course studies of CD14 and CD16 surface expression confirmed the rapid and coordinate up-regulation of these proteins. Thus, the intracellular compartment containing CD14 and CD16 had the properties of secretory vesicles. These vesicles may represent a specialized membrane domain of PMN enriched in GPI-anchored proteins.

Alkaline Phosphatase↗

T cell receptor V beta repertoire in an acute infection of rhesus monkeys with simian immunodeficiency viruses and a chimeric simian-human immunodeficiency virus.

Changes in T cell receptor (TCR) V beta repertoire and their correlation with virologic events were investigated in rhesus monkeys after acute infection with the simian immunodeficiency virus (SIV). 11 genetically defined rhesus monkeys were experimentally infected with SIVmac or a chimeric simian-human immunodeficiency virus (SHIV), and their peripheral blood lymphocytes (PBL) and lymph nodes were prospectively assessed for TCR V beta gene expression. PBL and lymph nodes of the acutely infected monkeys demonstrated an expansion of selected V beta-expressing T lymphocyte subpopulations as early as 3 d after infection. These expanded V beta-expressing lymphocyte subpopulations were comprised predominantly of CD8+ cells. Six of seven infected monkeys sharing a single electrophoretically defined major histocompatibility complex class I allele exhibited a similar expansion of V beta 14-expressing PBL. Sequence analyses of V-D-J segments of TCR-beta cDNA indicated that the V beta-expressing T cell subpopulation expansion can be oligoclonal. SIVmac-specific CD8+ cytotoxic T lymphocytes were demonstrated in both PBL and lymph nodes of the infected monkeys at the time expansion of the selected V beta-expressing cell subpopulations was seen. Finally, the expansion of the selected V beta-expressing lymphocytes in PBL coincided with the emergence and clearance of SIV p27 from the plasma of the infected monkeys. These results demonstrate that acute infection of rhesus monkeys with SIVmac or SHIV results in an expansion of CD8+ lymphocyte subpopulations expressing selected V beta gene families. The selectively expanded T lymphocytes may contribute to early viral clearance after acute SIVmac or SHIV infection.

Acute Disease↗

Receptors, signal transduction, and spectrum of action of monocyte chemotactic protein-1 and related chemokines.

Chemokines are a bipartite family of chemotactic proteins that bear the structural hallmark of four cysteine residues, the first two of which are in tandem. The spectrum of action of C-C chemokines, monocyte chemotactic protein-1 (MCP-1), MCP-2, and MCP-3, in particular, encompasses, in addition to monocytes, other leukocyte populations. Evidence is presented that MCP-1, MCP-2, and MCP-3 are active on natural killer cells. Available information on receptor usage by MCP-1 and related chemokines and signal transduction pathways is reviewed. A better understanding of signaling mechanisms will provide a new basis for therapeutic strategies.

Calcium↗

Quinolinic acid-induced increases in calbindin D28k immunoreactivity in rat striatal neurons in vivo and in vitro mimic the pattern seen in Huntington's disease.

In Huntington's disease striatal neurons undergo marked changes in dendritic morphology and coincidently exhibit an increase in immunoreactive calbindin D28k (calbindin), a cytosolic calcium-binding protein which is highly abundant in these neurons. Previous studies in the rat striatum have shown that excitotoxic injury, which is linked to a rise in intracellular Ca2+, mimics many of the neurochemical and neuropathological characteristics of Huntington's disease. We speculated, therefore, that the apparent increase in calbindin labeling in Huntington's disease spiny neurons may signal the response to an excitotoxic process. To investigate this possibility, we compared the cellular features of calbindin immunoreactivity in grade 1-4 Huntington's disease cases with those seen in rat striatal neurons in vivo and in vitro following treatment with N-methyl-D-aspartate (NMDA) receptor agonist, quinolinic acid. In human post mortem control cases calbindin immunoreactivity was seen primarily in the somata and proximal dendrites of striatal neurons. In the Huntington's disease cases, calbindin labeling was markedly increased throughout the second and third order dendrites and in spines, and this change was more prevalent in advanced cases (grades 3-4). In the rat brain, two weeks after intrastriatal injection of quinolinic acid (6-20 ng), surviving medium-spiny neurons in the transition zone around the lesion core exhibited a marked increase in calbindin immunoreactivity similar to that seen in Huntington's disease spiny neurons. In more peripheral areas away from the lesion and on the contralateral unlesioned side, calbindin immunostaining was confirmed to somata and proximal dendrites. In situ hybridization histochemistry with an 35S-labeled oligonucleotide probe showed no change or a decrease in calbindin mRNA levels in neurons within the transition zone, suggesting that the observed increase in calbindin staining was not the result of increased transcription. In 12 day old postnatal striatal cultures, 2-6 h exposures to quinolinic acid (0.5 mM) significantly increased the length of neurites exhibiting calbindin immunoreactivity when compared to untreated controls. This effect was blocked by the selective NMDA receptor blocker (+/-)-2-amino-5-phosphonopentanoic acid (AP-5), indicating that an NMDA receptor-mediated mechanism contributed to the change in staining pattern. Results in rats suggest that the subcellular redistribution of calbindin immunoreactivity observed in Huntington's disease spiny neurons may be related to an NMDA receptor-induced excitotoxic process. An increased availability of calbindin protein at dendrites and spines may reflect a greater demand for Ca2+ buffering precipitated by an abnormal rise in in intracellular Ca2+.

Adult↗

Suppression of lymphocyte mitogenesis in different rat strains exposed to footshock during early diurnal and nocturnal time periods.

The present study examined stressor interactions with genotype and light/dark cycle. Male Brown Norway (BN), Fischer 344 (F344), Lewis (from two different vendors: Lew/CR and Lew/H) and Sprague Dawley (SD) rats were exposed to footshock either in the early light or early dark circadian phase. Immediately after footshock, the spleen and whole blood proliferation to PHA and Con A was assessed. To provide endocrine indices of stress, serum was measured for corticosterone and interleukin-6 (IL-6). All rats showed significant increases in serum corticosterone and IL-6 following footshock either in the light or the dark. Rat strain differences were noted in the IL-6 response, while the corticosterone response was strong for all strains. The criterion for 'suppression' of lymphocyte proliferation was p < .05 (as determined by ANOVA) compared to non-shocked controls. Spleen: with the exception of BN rats, the other strains showed suppressed spleen cell proliferation to PHA and Con A both in the light and the dark. BN rats failed to show suppression of mitogenic activity to PHA when footshock was given in the light. Peripheral blood lymphocytes: suppression in Lew rats from either vendor, and in F344 and BN rats, did not vary with time of day nor with the type of mitogen tested. SD rats did not show suppression to PHA if shocked in the light. These results highlight the generality of stressor-induced mitogenic lymphocyte proliferation during the early diurnal and nocturnal periods of the day.

Animals↗

Helicobacter pylori infection and gastric metaplasia in the duodenum in China.

Biopsy specimens from antral and duodenal mucosa were obtained from 64 patients with active duodenal ulcer and from 78 with nonulcer dyspepsia. Gastric metaplasia in the duodenal bulb was more frequent in patients with duodenal ulcer (82.5%) than in patients with dyspepsia and duodenitis (53.1%) or in patients with dyspepsia without duodenitis (34.5%). Helicobacter pylori infection in the duodenal bulb was found more often in patients with moderate to severe gastric metaplasia (62.3%) than in patients with mild gastric metaplasia (20%). Therefore, patients from a developing country, China, showed the same relationship between duodenitis, gastric metaplasia, duodenal colonization with H. pylori, and duodenal ulcer previously demonstrated in developed countries.

Adolescent↗

Microheterogeneity of Neisseria lipooligosaccharide: analysis of a UDP-glucose 4-epimerase mutant of Neisseria meningitidis NMB.

Neisseria meningitidis is the etiologic agent of epidemic bacterial meningitis. Lipooligosaccharide (LOS) is a principal virulence factor associated with the organism, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of LOS has demonstrated that there is considerable microheterogeneity in the molecule. To begin our understanding of the nature of this heterogeneity, we identified a Tn916-generated LOS mutant of N. meningitidis NMB (serotype L3, monoclonal antibodies 3F11+, 6B4+, and 4C4-) that was designated NMB-SS3 (monoclonal antibodies 3F11-, 6B4-, and 4C4+). The transposon insertion was localized to the amino terminus of the functional copy of the UDP-Glc 4-epimerase gene (galE). UDP-Glc 4-epimerase (EC 5.1.3.2) activity was present in N. meningitidis NMB but not in NMB-SS3, indicating that the Tn916 insertion had abolished this activity. Mass spectrometric analysis of the LOS from strain NMB revealed multiple species of LOS, which is consistent with extensive microheterogeneity. While the most predominant structure was consistent with a terminal lacto-N-neotetrose structure found in other strains of N. meningitidis, Gal beta 1-->4GlcNAc beta 1-->3Gal beta 1-->4Glc-->(GlcNAc)-->Hep2PEA-->KDO2 (where Hep is heptose, PEA is phosphoethanolamine, and KDO is 2-keto-3-deoxymannooctulosonic acid), structures containing repetitive hexoses which are not precursors of this structure were also identified. Compositional analysis of LOS from strain NMB-SS3 revealed that there were no galactoses present in the structure. Mass spectrometric analysis of O-deacylated LOS revealed the presence of multiple species, with the predominant LOS species in this mutant strain formed by the Hex-->(HexNAc)-->Hep2PEA-->KDO2 (where Hex is hexose and HexNAc is N-acetylhexosamine) structure. However, LOS structures with repetitive hexoses, e.g., Hexn-->(HexNAc)-->Hep2PEA-->KDO2 (n = 2, 3, or 4), emanating from one or both heptoses were also identified. Since this mutant cannot synthesize UDP-Gal, these structures must repetitive glucoses. These data suggest that NMB has a glycosyltransferase capable of polymerizing glucose moieties as an alternative biosynthetic pathway to the wild-type lacto-N-neotetrose structure.

Base Sequence↗

Substance P (NK1)- and neurokinin A (NK2)-receptor gene expression in inflammatory airway diseases.

The tachykinin neuropeptides substance P and neurokinin (NK) A have been postulated to participate in the inflammatory reaction in airways of smokers and asthmatics. We have examined the hypothesis that the expression of one or more of the three cloned tachykinin receptors (NK1, NK2, and NK3) is increased in inflammatory airway disorders, which could result in augmentation of the effect of released tachykinin neuropeptides. NK1 receptor and NK2 receptor but not NK3-receptor mRNA were detected by ribonuclease protection assay in RNA from both cartilaginous and membranous bronchi and subpleural lung. In lung samples containing membranous airways, NK2-receptor mRNA expression was increased fourfold in asthmatics compared with nonsmoking controls, whereas NK1-receptor mRNA levels were similar in the two groups. NK1- and NK2-receptor mRNA expression was increased twofold in smokers without airflow obstruction compared with nonsmokers, whereas NK1-receptor mRNA expression was significantly lower in patients with chronic obstructive pulmonary disease compared with smoking controls. In situ hybridization indicated NK1-receptor mRNA was expressed in submucosal glands and airway epithelial cells, whereas NK2-receptor and NK3-receptor mRNA were not detected. These observations have implications for the pathophysiology and treatment of both asthma and tobacco smoke-induced airway inflammation.

Adult↗

Central administration of prostaglandin E2 suppresses in vitro cellular immune responses.

Research suggests that the regulation of the function of the immune system by the central nervous system (CNS) involves the integrative responses of multiple neural systems that affect neuroendocrine and sympathetic nervous systems. To determine whether prostaglandin E2 (PGE2) is involved in the modulatory mechanisms of immune system function, it was administered intracerebroventricularly (ICV) to conscious male rats. One hour later, spleen and peripheral blood lymphocytes were collected for culture with nonspecific mitogens. ICV administration of PGE2 decreased blood lymphocyte proliferative responses to the T-cell mitogens phytohemagglutinin and concanavalin A and decreased spleen lymphocyte proliferative responses to phytohemagglutinin and lipopolysaccharide (a B-lymphocyte mitogen). ICV administered PGE2 also stimulated the activity of the hypothalamic-pituitary-adrenal axis, as reflected by increased plasma concentrations of adrenocorticotropic hormone and corticosterone. Thus PGE2 may act in the CNS as a hormonal modulator of immune system function.

Adrenocorticotropic Hormone↗

On rural urbanization in China.

The author reviews "the debate regarding rural urbanization in the Chinese literature and the political factions that support different positions. He also introduces us to the complexity of defining ¿urbanization' in a Chinese context. He cautions us in the use of the common but important yardsticks for measuring basic data, such as growth in the officially registered urban population or an increase in the number of rurally registered people who change to nonagricultural registration status, that is, urban-registered status (nong zhuan fei)." A comparison of urbanization in different prosperous areas is made.

Asia↗

[The significance of immune island appeared in pleural and peritoneal effusion].

Macrophage surrounded by transformed or untransformed lymphocytes is called immune island. Aimming at this problem, we made a survey of 120 pleural and peritoneal effusion smears with a variety of patients and discovered that this island appeared in 52 (43.3%) cases. The positive results existed in 11 of 14 (79%) cases with tuberculosis and 29 of 60 (48%) cases with malignant diseases. The average number of island on each positive smear (2.0cm x 2.5cm) is 59.6 +/- 12.8 in the former and 39.2 +/- 18.9 in the latter. The mechanism of this phenomenon may be due to the response to foreign stimulus from pathogenic and cancer antigen.

Adolescent↗

[Study on the calibration model of electronystagmography (ENG) in the guinea pigs].

The passive calibration of ENG according to the gain of OKN evoked in guinea pigs was studied in this paper. The method was also verified by animal experiment and the comparison between active calibration and passive one in normal subjects. OKN was elicited by optokinetic drum with black and white strips at 10 intervals at velocity of 5-60 degrees/s. The calculating formula of passive calibration in animals obtained by mathematical corollary is K = G . ST sigma . DV/SA sigma. The slow-phase velocity of spontaneous nystagmus in a group of animals with acute loss of unilateral vestibular function recorded with this method showed typically a logarithmic decline within 24 hours. No significant difference between the values of active and passive calibration was found in normal subjects. The results demonstrated that the method described in the paper was accurate and reliable. It can be used in perivestibular experiments.

Animals↗

Epidemiology of Helicobacter pylori infection in the People's Republic of China.

This paper presents a general review of the studies on the epidemiology of H. pylori infection in China. Among 3,519 dyspeptic individuals presenting for endoscopy, H. pylori detectable rate was 61.2%. A higher prevalence of infection was found in patients with peptic ulcer. The prevalence of gastric metaplasia was 82.5% in patients with duodenal ulcer, 53.1% in duodenitis and 34.5% in normal duodenal mucosa. H. pylori infection is significantly more common in gastric cancer patients (58.9%) than in the matched controls (42.5%). Endoscopic studies performed on asymptomatic volunteers aged 10-25 showed that the prevalence of gastritis and H. pylori was 45%-84% and 42%-67% respectively. Large scale prospective studies of the possible role of H. pylori in gastric cancer in populations with various gastric cancer mortality rates using ELISA assays showed a significant geographical association between gastric cancer mortality and the prevalence of H. pylori infection. H. pylori infection is acquired at an earlier age and has a higher prevalence in the high gastric cancer risk areas than in the low risk areas. H. pylori was detected in human saliva and dental plaque by PCR. H. pylori-like organisms were successfully isolated by culture and detected by nested PCR in the gastric mucosa of pigs and cats. Intrafamilial clustering of H. pylori infection was observed.

China↗

Acute gastritis associated with infection of large spiral-shaped bacteria.

We report a case of gastric colonization of large spiral-shaped bacteria in a patient with acute gastritis. Endoscopy showed an acute erosive and hemorrhagic gastroduodenitis. Histopathological examination of antral biopsies revealed intense neutrophil infiltrates with microabscesses. Numerous large spiral-shaped bacteria were seen in the Gram-stained smear of the gastric biopsy. The patient was treated with colloidal bismuth subcitrate and cimetidine. Biopsy taken after treatment showed resolution of infection and histological gastritis. The results provide further evidence that large spiral-shaped bacteria are another infective cause of acute neutrophilic gastritis in humans.

Acute Disease↗

[A clinical and experimental study of L-form bacteria in 66 cases].

In order to study the relationship between the time for establishing the diagnosis of infectious diseases and L-form bacteria, a series of clinical specimens taken from 321 cases of patients suspected to have infection were collected. Besides routine bacterial culture, special culture for L-form bacteria was also performed. The results were as follows: the rate of positive routine bacterial culture was 10.90% (35/321); the rate of negative routine bacterial culture but positive L-form bacterial culture was 20.56% (66/321). In this study, L-form bacteria infection was treated with sensitive antibiotics and a satisfactory result was obtained. It is shown that L-form bacterial culture is very useful in detection of pathogenic bacteria and helpful to the therapy of infectious diseases. Ultrastructure organization of these bacteria was studied by using transmission electron microscope.

Adult↗