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Biomedical subjects

Ping Han

Publications and source records attributed to Ping Han.

6 recordsLinked to original sources

Capsaicin infused into the PAG affects rat tail flick responses to noxious heat and alters neuronal firing in the RVM.

It is well established that the vanilloid receptor, VR1, is an important peripheral mediator of nociception. VR1 receptors are also located in several brain regions, yet it is uncertain whether these supraspinal VR1 receptors have any influence on the nociceptive system. To investigate a possible nociceptive role for supraspinal VR1 receptors, capsaicin (10 nmol in 0.4 microl) was microinjected into either the dorsal (dPAG) or ventral (vPAG) regions of the periaqueductal gray. Capsaicin-related effects on tail flick latency (immersion in 52 degrees C water) and on neuronal activity (on-, off-, and neutral cells) in the rostral ventromedial medulla (RVM) were measured in lightly anesthetized rats. Administration of capsaicin into the dPAG but not the vPAG caused an initial hyperalgesic response followed later by analgesia (125 +/- 20.96 min postinjection). The tail flick-related burst in on-cell activity was triggered earlier in the hyperalgesic phase and was delayed or absent during the analgesic phase. Spontaneous activity of on-cells increased at the onset of the hyperalgesic phase and decreased before and during the analgesic phase. The tail flick-related pause in off-cell activity as well as spontaneous firing for these cells was unchanged in the hyperalgesic phase. During the analgesic phase, off-cells no longer paused during noxious stimulation and had increased levels of spontaneous activity. Neutral cell firing was unaffected in either phase. Pretreatment with the VR1 receptor antagonist, capsazepine (10 nmol in 0.4 microl), into the dPAG blocked the capsaicin-induced hyperalgesia as well as the corresponding changes in on- and off-cell activity. VR1 receptor immunostaining was observed in the dPAG of untreated rats. Microinjection of capsaicin likely sensitized and then desensitized dPAG neurons affecting nocifensive reflexes and RVM neuronal activity. These results suggest that supraspinal VR1 receptors in the dPAG contribute to descending modulation of nociception.

Action Potentials↗

A marked decrease in L-selectin expression by leucocytes in infants with Bordetella pertussis infection: leucocytosis explained?

OBJECTIVE: Infants with Bordetella pertussis infection (whooping cough) have an unexplained lymphocytosis and leucocytosis characterized by an increase in small lymphocytes with convoluted and cleaved nuclei. To characterize these cells immunophenotyping using multiparameter flow cytometry was performed on leucocytes from a group of 11 infants aged 3-6 months with proven pertussis and from uninfected control subjects. METHODOLOGY: The panel of monoclonal antibodies used to elucidate leucocyte subtypes included activation, adhesion, costimulatory, memory, T-helper (Th) 1 and Th2 markers. RESULTS: Patients with pertussis showed an increase in absolute numbers of neutrophils, monocytes, T lymphocytes (both CD4 and CD8), B lymphocytes (including CD10+/CD19+ haematogones) and natural killer (NK) cells. All leucocyte subgroups showed a marked decrease in L-selectin (CD62L) expression. The expression of other adhesion molecules CD11a, CD44 and CD54 on all leucocyte subgroups was unchanged. Expression of costimulatory molecules, CD49D and CD28 on T cells and CD80 and CD86 on monocytes, was unchanged. Lymphocyte activation markers CD69, CD25 and HLA-DR were unchanged. There was an increase in CD45RA+/CD45RO+/CD4+ cells (activated) and CD62L-/CD45RO+/CD4+ cells (Th1-like) but no increase in CD7-/CD4+ T cells (Th2-like). CONCLUSIONS: L-Selectin expression mediates extravasation of leucocytes into tissues and is important for homing of peripheral blood lymphocytes to lymph nodes. The significant down-regulation of L-selectin on leucocytes in pertussis infection may prevent leucocyte migration to areas of infection and homing and adhesion of T and B cells to peripheral lymphoid tissues. The increase in lymphocytes with Th1 phenotype may be required for effective immune response to the infective organism. These data provide a possible explanation for the absolute leucocytosis observed in this disease.

Antibodies, Monoclonal↗

Malate synthase gene expression during fruit ripening of Cavendish banana (Musa acuminata cv. Williams).

Malate synthase (MS) is a key enzyme responsible for malic acid synthesis in the glyoxylate cycle, which functions to convert stored lipids to carbohydrates, by catalysing the glyoxylate condensation reaction with acetyl-CoA in the peroxisome. In this study, the cloning of an MS cDNA, designated MaMS-1, from the banana fruit is reported. MaMS-1 was 1801 bp in length encoding a single polypeptide of 556 amino acid residues. Sequence analysis revealed that MaMS-1 possessed the conserved catalytic domain and a putative peroxisomal targeting signal SK(I/L) at the carboxyl terminal. MaMS-1 also shared an extensive sequence homology (79-81.3%) with other plant MS homologues. Southern analysis indicated that MS might be present as multiple members in the banana genome. In Northern analysis, MaMS-1 was expressed specifically in ripening fruit tissue and transcripts were not detected in other organs such as roots, pseudostem, leaves, ovary, male flower, and in fruit at different stages of development. However, the transcript abundance in fruit was affected by stage of ripening, during which transcript was barely detectable at the early stage of ripening (FG and TY), but the level increased markedly in MG and in other fruits at advanced ripening stages. Furthermore, MaMS-1 expression in FG fruit could be stimulated by treatment with 1 microl l(-1) exogenous ethylene, but the stimulatory effect was abolished by the application of an ethylene inhibitor, norbornadiene. Results of this study clearly show that MS expression in banana fruit is temporally regulated during ripening and is ethylene-inducible.

Amino Acid Sequence↗

Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: potential therapeutic use in the treatment of inflammatory bowel disease.

BACKGROUND: Cytokines involved in inflammatory bowel disease (IBD) direct a predominantly cell-mediated T- helper-1 (Th1) immune response. The nonspecific anti-inflammatory treatment being used in the management of patients with IBD has not changed much since the 1970s and new therapeutic agents are keenly sought. Several compounds isolated from Allium sativum (garlic) modulate leukocyte cell proliferation and cytokine production. METHODS: To investigate the possible therapeutic effects of garlic in the treatment of patients with IBD, whole blood and peripheral blood mononuclear cells (PBMCs) were stimulated in the presence of various concentrations of garlic extract and the effect on leukocyte cytokine production was determined in vitro using multiparameter flow cytometry. RESULTS: Monocyte interleukin (IL)-12 production was inhibited significantly in the presence of low concentrations of garlic extract (>or=0.1 microg/ml total protein). Monocyte IL-10 production increased significantly and monocyte tumor necrosis factor-alpha (TNF-alpha), IL-1alpha, IL-6, IL-8, T-cell interferon-gamma (IFN-gamma), IL-2, and TNF-alpha decreased significantly in the presence of >or=10 microg/ml garlic extract. Twenty to fifty percent of the immunomodulatory activity of garlic extract on cytokine production was acid labile. The inhibitory activity of methylprednisolone, a commonly used anti-inflammatory in IBD, with garlic on leukocyte cytokine production was additive. CONCLUSIONS: By inhibiting Th1 and inflammatory cytokines while upregulating IL-10 production, treatment with garlic extract may help to resolve inflammation associated with IBD. An in vivo animal model study needs to be undertaken to determine the significance of these in vitro findings.

Anti-Inflammatory Agents↗

Presenilin 1 is required for maturation and cell surface accumulation of nicastrin.

Proteolytic processing of amyloid precursor protein generates beta-amyloid (Abeta) peptides that are deposited in senile plaques in brains of aged individuals and patients with Alzheimer's disease. Presenilins (PS1 and PS2) facilitate the final step in Abeta production, the intramembranous gamma-secretase cleavage of amyloid precursor protein. Biochemical and pharmacological evidence support a catalytic or accessory role for PS1 in gamma-secretase cleavage, as well as a regulatory role in select membrane protein trafficking. In this report, we demonstrate that PS1 is required for maturation and cell surface accumulation of nicastrin, an integral component of the multimeric gamma-secretase complex. Using kinetic labeling studies we show that in PS1(-/-)/PS2(-/-) cells nicastrin fails to reach the medial Golgi compartment, and as a consequence, is incompletely glycosylated. Stable expression of human PS1 restores these deficiencies in PS1(-/-) fibroblasts. Moreover, membrane fractionation studies show co-localization of PS1 fragments with mature nicastrin. These results indicate a novel chaperone-type role for PS1 and PS2 in facilitating nicastrin maturation and transport in the early biosynthetic compartments. Our findings are consistent with PS1 influencing gamma-secretase processing at multiple steps, including maturation and intracellular trafficking of substrates and component(s) of the gamma-secretase complex.

Amyloid Precursor Protein Secretases↗

Lung function imaging under quantitative spirometrically controlled CT.

OBJECTIVE: To assess the possibility of using spirometrically controlled computed tomography (CT) to test pulmonary ventilation function. METHODS: Spiral CT scans under the control of a spirometer were performed on 30 healthy adults. Spiral CT scan was performed at 50% vital capacity (VC) with an 8 mm slice thickness. Mean attenuation values and pixel index (PI) of lung regions were evaluated with semiautomatic evaluation software. RESULTS: There were significant differences in PI values between four pixel intervals. CONCLUSIONS: Spirometrically controlled spiral CT with semiautomatic evaluation software is an accurate and reproducible method of measuring lung density and PI, which has the possibility of indicating pulmonary ventilation function.

Adult↗