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Biomedical subjects

R Guo

Publications and source records attributed to R Guo.

At least 91 records · Page 5Linked to original sources

Monocarboxylic-based phosphotyrosyl mimetics in the design of GRB2 SH2 domain inhibitors.

Three monocarboxylic-containing analogues, O-carboxymethyltyrosine (cmT, 5), 4-(carboxymethyl)phenylalanine (cmF, 6), and 4-(carboxydifluoromethyl)phenylalanine (F2cmF, 7) were utilized as phosphotyrosyl (pTyr) replacements in a high affinity B-bend mimicking platform, where they exhibited IC50 values of 2.5 microM, 65 microM and 28 microM, respectively, in a Grb2 SH2 domain Biacore binding assay. When a terminal N(alpha)-oxalyl axillary was utilized to enhance ligand interactions with a critical SH2 domain Arg67 residue (alphaA-helix), binding potencies increased from 4- to 10-fold, resulting in submicromolar affinity for cmF (IC50 = 0.6 microM) and low micromolar affinity for F2cmF (IC50 = 2 microM). Cell lysate binding studies also showed inhibition of cognate Grb2 binding to the p185erbB-2 phosphoprotein in the same rank order of potency as observed in the Biacore assay. These results indicate the potential value of cmF and F2cmF residues as pTyr mimetics for the study of Grb2 SH2 domains and suggest new strategies for improvements in inhibitor design.

Adaptor Proteins, Signal Transducing↗

Abnormalities of enteric neurons, intestinal pacemaker cells, and smooth muscle in human intestinal atresia.

BACKGROUND/PURPOSE: Intestinal dysmotility, which usually has been encountered in the severely dilated proximal segment, is an important problem in postoperative management of patients with intestinal atresia (IA). Changes of enteric nerves had been histochemically examined in both the proximal and distal segments of IA, but a systemic immunohistochemical analysis is still lacking. The aim of this study was to examine precisely alterations of neuronal and muscular elements and pacemaker cells in intestines from patients with IA. METHODS: Resected intestines were obtained from 5 patients with ileal atresia, 3 patients with jejunal atresia, and 3 controls without gastrointestinal diseases (congenital diaphragmatic hernia). All specimens were immunochemically stained with a monoclonal antibody to alpha-smooth muscle actin (SMA) as a smooth muscle marker, polyclonal antibodies to protein gene product (PGP) 9.5 as a general neuronal marker, and to c-kit protein as a maker of intestinal pacemaker cells. In addition, all specimens also were stained by NADPH-diaphorase (NADPH-d) to know the distribution of inhibitory nitrergic nerves. RESULTS: A hypoplasia of the myenteric ganglia and a marked reduction of intramuscular nerve fibers, including nitrergic neurons, were observed in the dilated proximal segment of IA. C-kit-positive cells were localized around the myenteric plexus, but rarely found within the muscularis propria in the proximal segment. The distribution of nerves and c-kit-positive cells in the distal segment was comparable with that seen in controls. A reduced staining intensity for alpha-SMA was mainly observed in the hypertrophic circular muscle layer of the proximal segment. CONCLUSIONS: A hypoplasia of intramural nerves and pacemaker cells was seen predominantly in the proximal segments of IA. Hypertrophy and reduced immunoreactivity for alpha-SMA also were observed in the circular muscle layer of the proximal segment. These alterations of the proximal segment may thus contribute to the postoperative intestinal dysmotility in IA cases.

Actins↗

Chronological change of distribution in nitric oxide and peptidergic neurons after rat small intestinal transplantation.

BACKGROUND/PURPOSE: Nitric oxide (NO) has been considered one of the putative neurotransmitters of nonadrenergic, noncholinergic inhibitory neurons. To examine the effect of transplantation on NO neurons in the intestine, the distribution of NO neurons was examined and compared with that of peptide-containing neurons. METHODS: A jejunal graft measuring about 20 cm was harvested from a Lewis rat, syngeneically transplanted as a Thiry-Vella loop, and later was replaced to the recipient small bowel 20 days after transplantation. Tissue specimens of the grafts were taken on days 1, 3, 6, 10, and 20, and 1 year after transplantation (n = 5 each). The distribution of the neurons was examined immunohistochemically, using antisera against protein gene product 9.5 (PGP 9.5, general neuronal marker), brain nitric oxide synthase (bNOS), vasoactive intestinal polypeptide (VIP), and substance P. In addition, NADPH diaphorase staining also was performed to visualize NO neurons. RESULTS: In the PGP 9.5 immunoreactivities, no significant difference in the distribution was observed among the controls and on any day after transplantation. However, the NADPHd activities markedly decreased in muscle layers, especially in the deep muscular layer on day 1 and 3, but quickly recovered by day 6. The distribution of bNOS immunoreactivities was almost same as that of NADPHd staining. The VIP and substance P immunoreactivities also decreased on day 1, and thereafter gradually recovered, and then became normal on day 20. CONCLUSIONS: Both the NO and peptidergic neurons markedly decreased just after transplantation, and the NO neurons recovered faster than the peptidergic neurons. These findings suggested that NO neurons might play an important role in the adaptation process of the graft in the early period after transplantation.

Animals↗

Alterations of the intramural nervous distributions in a chick intestinal atresia model.

The postoperative intestinal dysmotility seen in intestinal atresia (IA) is usually found in association with a dilatation of the proximal intestinal segment, but the etiology of this disorder is not yet fully understood. A chick IA model was made by cutting the postumbilical midgut on d 11 in ovo. The operated chicks were euthanized 2 d after hatching. The samples were divided into two groups according to the extent of the dilatation of proximal ileal segments. Cryostat sections were processed for immunohistochemistry by the use of antisera to protein gene product 9.5, vasoactive intestinal polypeptide, substance-P, and alpha-smooth muscle actin and were also stained by NADPH-diaphorase. Tn highly dilated proximal segments, a decreased number of protein gene product 9.5-positive fibers was found in both the circular muscle and submucous layers. The number of nerve fibers positive for vasoactive intestinal polypeptide, substance-P, and NADPH-diaphorase also decreased in the circular muscle layer, particularly in the deep muscular plexus. Hypertrophy and an alteration of the staining intensities in the circular muscle layer were also revealed by a-smooth muscle actin staining. The nerve distribution of the distal segments was indistinguishable from that of the age-matched controls and the sham-operated group. Abnormalities in the intramural nerves are only found in the proximal ileal segment of the IA models. The abnormal nerve distribution of the proximal segment might thus be implicated in the postoperative dysmotility of the intestine in IA.

Actins↗

Regulatory effects of interleukin-11 during acute lung inflammatory injury.

The role of interleukin-11 (IL-11) was evaluated in the IgG immune complex model of acute lung injury in rats. IL-11 mRNA and protein were both up-regulated during the course of this inflammatory response. Exogenously administered IL-11 substantially reduced, in a dose-dependent manner, the intrapulmonary accumulation of neutrophils and the lung vascular leak of albumin. These in vivo anti-inflammatory effects of IL-11 were associated with reduced NF-kappaB activation in lung, reduced levels of tumor necrosis factor alpha (TNF-alpha) in bronchoalveolar lavage (BAL) fluids, and diminished up-regulation of lung vascular ICAM-1. It is interesting that IL-11 did not affect BAL fluid content of the CXC chemokines, macrophage inflammatory protein-2 (MIP-2) and cytokine-inducible neutrophil chemoattractant (CINC); the presence of IL-11 did not affect these chemokines. However, BAL content of C5a was reduced by IL-11. These data indicate that IL-11 is a regulatory cytokine in the lung and that, like other members of this family, its anti-inflammatory properties appear to be linked to its suppression of NF-kappaB activation, diminished production of TNF-alpha, and reduced up-regulation of lung vascular ICAM-1.

Animals↗

[Evolution of conception on apoplexoid (lei zhong feng) disorder].

Viewing separately from the etiology and the disease itself, the ancient literature gave two definitions, totally different from each other, for apoplexoid disorders within the category of apoplexy, each experienced a process of starting, development and evolution stages. Both exerted an active promotion to the development of apoplexy.

Cerebrovascular Disorders↗

[Determination of sarafloxacin by high performance liquid chromatography (HPLC)].

A method for the separation and determination of Sarafloxacin by HPLC was developed. The sample was dissolved in a mixture of V(acetonitrile):V(water) = 1:1. Operating conditions were as follows: mu-Bondapak C18 column (3.9 mm x 300 mm), V(acetonitrile):V(methanol):V(2 mmol/L H3PO4, adjust pH 3.5 with triethylamine) = 30:5:65 as mobile phase with a flow rate of 1 mL/min, UV detection at 278 nm, and column temperature was 15 degrees C. Under the above conditions, Sarafloxacin and other impurities were separated from each other. The method was simple, rapid, sensitive and accurate.

Anti-Infective Agents↗

[Sensitizing effect of nonionic microemulsion on phosphorus in crystal violet heteropoly molybdophosphoric acid].

A highly sensitive and convenient spectrophotometric method for phosphorus was developed. The sensitizing effect of nonionic microemulsion Triton X-100/n-C5H11OH/n-C0H20/H2O on the ion-association of heteropoly molybdophosphoric acid with crystal violet was higher than that of micelle Triton X-100/H2O. This result showed, by the measurement of distribution constant KD, that the binding constant K and the number of binding sites n of CV were related to the greater solubilization capacity of CV-PMo in nonionic microemulsion system than that in micelle.

English Abstract↗

[Sensitizing effect of nonionic microemulsion on the derivative spectrophotometric determination of trace iron with sulfosalicylic acid].

The sensitizing effect of O/W microemulsion of Triton X-100/n-C5H11OH/n-C9H20/H2O as a medium on the derivative spectrophotometry of Fe-Sal was studied. The results show that the sensitivity of determination in O/W microemulsion was higher than that in micelle. The reagent Sal has higher distribution coefficient KD and constant K in microemulsion than in the micelle system and lower binding in O/W microemulsion than in the micelle system. This results also illustrate that O/W microemulsion has more solubilization for Sal than micelle does, so that O/W microemulsion has more sensitizing reaction than micelle does.

English Abstract↗

LIGHT, a novel ligand for lymphotoxin beta receptor and TR2/HVEM induces apoptosis and suppresses in vivo tumor formation via gene transfer.

LIGHT is a new member of tumor necrosis factor (TNF) cytokine family derived from an activated T cell cDNA library. LIGHT mRNA is highly expressed in splenocytes, activated PBL, CD8(+) tumor infiltrating lymphocytes, granulocytes, and monocytes but not in the thymus and the tumor cells examined. Introduction of LIGHT cDNA into MDA-MB-231 human breast carcinoma caused complete tumor suppression in vivo. Histological examination showed marked neutrophil infiltration and necrosis in LIGHT expressing but not in the parental or the Neo-transfected MDA-MB-231 tumors. Interferon gamma (IFNgamma) dramatically enhances LIGHT-mediated apoptosis. LIGHT protein triggers apoptosis of various tumor cells expressing both lymphotoxin beta receptor (LTbetaR) and TR2/HVEM receptors, and its cytotoxicity can be blocked specifically by addition of a LTbetaR-Fc or a TR2/HVEM-Fc fusion protein. However, LIGHT was not cytolytic to the tumor cells that express only the LTbetaR or the TR2/HVEM or hematopoietic cells examined that express only the TR2/HVEM, such as PBL, Jurkat cells, or CD8(+) TIL cells. In contrast, treatment of the activated PBL with LIGHT resulted in release of IFNgamma. Our data suggest that LIGHT triggers distinct biological responses based on the expression patterns of its receptors on the target cells. Thus, LIGHT may play a role in the immune modulation and have a potential value in cancer therapy.

Apoptosis↗

Monitoring of acute allograft rejection by cytological, immunocytochemical, and immunohistochemical studies following rat small-bowel transplantation.

We investigated the role of graft luminal fluid cytology for immunological monitoring of rat small-bowel allograft recipients. Allogeneic transplantation from WKAM (RT1u) to Lewis recipients and syngeneic transplantation using Lewis (RT11) rats were carried out. Twenty centimeters of the proximal jejunum was transplanted as a Thiry-Vella loop. The luminal fluid on days 0, 3, and 6 was examined cytologically using Papanicolaou, periodic acid-Schiff, and Giemsa staining, and immunocytochemically with monoclonal antibodies for macrophages (ED1 and ED2). Full thickness biopsies of graft tissue were evaluated by both immunofluorescence (ED1 and ED2) and by standard histological methods. The cytological examination on day 6 revealed an increase in the number of enterocytes, lymphocytes, and neutrophils, the presence of bacteria, and the depletion of goblet cells in the allografts. Histologically, significant morphological changes of acute rejection were first seen on day 6. Immunofluorescence predicted the acute rejection of the allografts earlier than a histological examination by showing an increase in the number of ED1- and Ed2-positive cells on day 3. Graft luminal fluid cytology and immunofluorescence analysis of ED1 and ED2 cells could thus be used to recognize early acute allograft rejection following small-bowel transplantation.

Animals↗

Intrinsic mineralization defect in Hyp mouse osteoblasts.

X-linked hypophosphatemia (XLH) is caused by inactivating mutations of PEX, an endopeptidase of uncertain function. This defect is shared by Hyp mice, the murine homologue of the human disease, in which a 3' Pex deletion has been documented. In the present study, we report that immortalized osteoblasts derived from the simian virus 40 (SV40) transgenic Hyp mouse (TMOb-Hyp) have an impaired capacity to mineralize extracellular matrix in vitro. Compared with immortalized osteoblasts from the SV40 transgenic normal mouse (TMOb-Nl), osteoblast cultures from the SV40 Hyp mouse exhibit diminished 45Ca accumulation into extracellular matrix (37 +/- 6 vs. 1,484 +/- 68 counts . min-1 . microgram protein-1) and reduced formation of mineralization nodules. Moreover, in coculture experiments, we found evidence that osteoblasts from the SV40 Hyp mouse produce a diffusible factor that blocks mineralization of extracellular matrix in normal osteoblasts. Our findings indicate that abnormal PEX in osteoblasts is associated with the accumulation of a factor(s) that inhibits mineralization of extracellular matrix in vitro.

Alkaline Phosphatase↗

RT-PCR study of the distribution of connexin 43 mRNA in the glomerulus and renal tubular segments.

An RT-PCR study of the distribution of connexin 43 (Cx43) mRNA in glomeruli and along the rat tubular segments was carried out to establish the differential expression of Cx43 in the different segments of the tubule, in renal regions, in isolated glomerular preparations (IGP), and in microdissected glomeruli. The mRNA level of Cx43 in macrodissected renal regions appeared in the following order: inner papilla > outer papilla and IGP > outer medulla and cortex. Among the microdissected tubules, inner medullary collecting ducts (IMCD) expressed the highest level of Cx43 mRNA, followed by the cortical collecting ducts (CCD). The proximal convoluted tubules and proximal straight tubules expressed significantly less Cx43 than the IMCD, glomeruli, and CCD. Medullary thick ascending limb and distal convoluted tubules showed the lowest level of Cx43 mRNA. The RT-PCR results of the microdissected segments correlate well with those obtained by RT-PCR of the renal regions. The high concentration of Cx43 mRNA in the IMCD together with the observation of abundant punctate immunofluorescence for Cx43 suggests that the IMCD not only expresses Cx43 mRNA but also that the mRNA is translated to Cx43 protein.

Animals↗

Cellular composition and anatomic distribution in nonfunctioning pancreatic endocrine tumors: immunohistochemical study of 30 cases.

OBJECTIVE: To investigate the cytological pattern and distribution in nonfunctioning pancreatic endocrine tumors. METHODS: Using labeled streptavidin-biotin (LSAB), immunohistochemical staining for insulin, glucagon, somatostatin, pancreatic polypeptide and gastrin was performed on 30 nonfunctioning pancreatic endocrine tumors from 30 patients. The cellular composition and anatomic distribution in these tumors were analyzed. RESULTS: Of 30 tumor tissues, 22 (73.3%) were found to contain cells immunoreactive to 1-4 kinds of peptide hormones; 17 (56.7%) showed positive staining for more than one peptide and up to 4 peptides; and 8 (26.7%) showed negative immunoreaction to all antiserum applied. No tumor was found to contain immunoreactive gastrin. Among 17 multihormonal tumors, 4 contained 2 kinds of peptide hormones, 8 had 3 kinds, and 5 harbored 4 kinds of peptide hormones. In addition, the difference in the number and type of positive endocrine cells between the tumors arising from the head of the pancreas and those arising from the body and tail of the pancreas were statistically significant (P < 0.05). CONCLUSIONS: Immunohistochemically, the high positive rate to peptide hormones suggests that the nonfunctioning pancreatic endocrine tumors are actually not nonfunctioning; they are asymptomatic pancreatic endocrine tumors. Moreover, an uneven distribution of positive endocrine cells in the nonfunctioning pancreas endocrine tumors within the pancreas was identified.

Adenoma, Islet Cell↗

[Histopathological study of surgical resection margins of laryngeal carcinoma].

64 specimens of laryngeal carcinoma were studied by using the step-serial whole organ section and histopathologic examination of the region around tumor. We discussed the situation of lesions spreading from tumor to resection margins, the survival rate of different types of resection margins, the common position of positive resection margins and the correlative factors of positive resection margins combining with histopathology, clinical expression and follow-up results. We concluded that resection margins more than 5 mm far from visible tumor is suitable.

Adult↗

[The observation on infection of trasgenic mice (PVR Tg21) with polioviruses type 3].

OBJECTIVE: To test and verify whether PVR Tg21 transgenic mice can be used as an animal model or not. METHODS: PVR Tg21 transgenic mice were infected with 3 poliovirus strains with different neurovirulence intraspinally. RESULTS: All the mice showed clinical paralysis with characteristic lesions in neurons. The symptoms varied with different potency of virus. The onset of clinical paralysis time for inoculated mice were approximately 2 days with Leon virus, 5 days with Sabin strain, and 4 days with Vaccine-321. More than 90% of mice inoculated with Leon strain died within 3 days after clinical paralysis and only 35% mice inoculated with Sabin-3 died at average of 6 days, and the PD50 are 10(1.1), 10(2.6), and 10(4.97) TCID50 and LD50 are 10(1.1), 10(3.33) and 10(5.33) TCID50, respectively. Different virus inoculated intraspinally caused different histopathological lesions. CONCLUSIONS: The PVR Tg21 transgenic mice could be a new animal model for neurovirulent evaluation of poliovaccines and epidemiological surveillance.

Animals↗