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Biomedical subjects

R Guo

Publications and source records attributed to R Guo.

At least 19 recordsLinked to original sources
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

The distribution and co-localization of nitric oxide synthase and vasoactive intestinal polypeptide in nerves of the colons with Hirschsprung's disease.

The distribution and co-localization of nitric oxide synthase (NOS) and vasoactive intestinal polypeptide (VIP) were examined by means of immunohistochemistry and NADPH diaphorase (NADPH-d) histochemistry in the gut of patients with Hirschsprung's disease. In the normoganglionic segment, many nitrergic nerve cells were localized in Auerbach's plexus and nerve fibres were observed preferentially in the circular muscle. The submucosal nitrergic nerve cells were mainly situated in Schabadasch's plexus with occasional cells demonstrable in Meissner's plexus. NOS and VIP were co-localized in most ganglion cells of Auerbach's plexus. In the oligoganglionic segment, a marked reduction of NOS- and VIP- positive nerve cells and fibres was noticed in both the myenteric and submucosal plexuses, and nitrergic fibres had disappeared in the inner layer of the circular muscle. In the aganglionic segment, NOS and VIP were revealed only in extrinsic nerve fasciculi and rami and co-localized in a few fibres. From these observations, the inner layer of the circular muscle of the oligoganglionic segment and the whole of the muscularis propria of the aganglionic segment were considered to be totally lacking in nitrergic innervation. Nitrergic nerves of the human colon comprise both intrinsic and extrinsic elements and the majority of intrinsic nitrergic nerve cells contain VIP. Very low numbers of extrinsic nitrergic fibres contain VIP.

Child↗
PubMed1997

Physical localization of rRNA genes by two-colour fluorescent in-situ hybridization and sequence analysis of the 5S rRNA gene in Phalaris coerulescens.

The 18S-5.8S-26S rDNA and 5S rDNA loci have been mapped physically by fluorescent in-situ hybridization to the chromosomes of Phalaris coerulescens. The biotin-labelled heterologous 18S-5.8S-26S rRNA probe (pTa71) detected one locus, which corresponded to the secondary constriction (nucleolar organizer) on the long arm of the satellited chromosome II. The homologous 5S rDNA probe (Bam2.12) detected two pairs of 5S rRNA gene clusters which were localized at two different non-satellited chromosomes, one near the telomere on the short arm of the chromosome I, which is the largest chromosome of the complement, and the other about 42% out on the long arm of the chromosome III. A BamHI fragment containing the 5S rRNA gene, has been isolated and characterized. The 5S rDNA repeat unit is 309 bp in length, consisting of 121 bp highly conserved coding region and 188 bp variable spacer region. The karyotype of Phalaris coerulescens is characterized by the similar size of chromosomes within the group 2, group 3, or group 4. This study represents the first step towards the understanding the genome organization of Phalaris coerulescens and provides reliable markers for chromosome identification in this grass, an important species as a model system for the study of self-incompatibility in grasses.

Base Sequence↗
PubMed1997

Putative analgesic activity of repeated oral doses of vitamin E in the treatment of rheumatoid arthritis. Results of a prospective placebo controlled double blind trial.

OBJECTIVE: Vitamin E, the most potent naturally occurring lipid soluble antioxidant has been suggested to possess both anti-inflammatory and analgesic activity in humans. This double blind and randomised study used a broad spectrum of clinical and laboratory parameters to investigate whether there was any additional anti-inflammatory or analgesic effects, or both, of orally administered alpha-tocopherol in rheumatoid arthritis patients who were already receiving anti-rheumatic drugs. METHODS: Forty two patients were enrolled and treated with alpha-tocopherol (n = 20) at a dose of 600 mg twice a day (2 x 2 capsules) or with placebo (n = 22) for 12 weeks. The following parameters were measured: (1) Three clinical indices of inflammation--the Ritchie articular index, the duration of morning stiffness, and the number of swollen joints; (2) three measures of pain--pain in the morning, pain in the evening, and pain after chosen activity; (3) haematological and biochemical measures of inflammatory activity; (4) assays for the oxidative modification of proteins and lipids. RESULTS: All laboratory measures of inflammatory activity and oxidative modification were unchanged. Furthermore, the clinical indices of inflammation were not influenced by the treatment. However, the pain parameters were significantly decreased after vitamin E treatment when compared with placebo. CONCLUSION: The results provide preliminary evidence that vitamin E may exert a small but significant analgesic activity independent of a peripheral anti-inflammatory effect, but which complements standard anti-inflammatory treatment.

Administration, Oral↗
PubMed1997

A distinct cation-sensing mechanism in MC3T3-E1 osteoblasts functionally related to the calcium receptor.

The presence of a cation-sensing mechanism in osteoblasts is suggested by the ability of specific cations to stimulate osteoblastic proliferation in culture and to induce de novo bone formation in some experimental models. Our study examines whether extracellular cations stimulate osteoblasts through the recently identified G protein-coupled calcium receptor (CaR). We found that CaR agonists, calcium (Ca2+), gadolinium (Gd3+), aluminum (Al3+), and neomycin, stimulated DNA synthesis in murine-derived MC3T3-E1 preosteoblasts, whereas magnesium (Mg2+), nickel (Ni2+), cadmium (Cd2+), and zinc (Zn2+) had no effect. With the exception of Mg2+, the cation specificities and apparent affinities were similar to that reported for CaR. CaR agonists also stimulated DNA synthesis in C3HT10(1/2) fibroblasts, but not in mesangial PVG, CHO, hepatic HTC, COS-7 cells, or malignant transformed ROS17/2.8 and UMR-106 osteoblasts. In addition, similar to other growth factors, CaR agonists activated transcription of a serum response element luciferase reporter construct (SRE-Luc) stably transfected into MC3T3-E1 osteoblasts, but had no effect on SRE-Luc transfected into CHO and COS-7 cells. We were unable to detect CaR expression by Northern analysis using a mouse CaR-specific probe or to amplify CaR mRNA by reverse transcribed polymerase chain reaction in MC3T3-E1 osteoblasts. These findings suggest that an extra-cellular cation-sensing mechanism is present in murine-derived osteoblasts that is functionally similar to but molecularly distinct from CaR.

Amino Acid Sequence↗
PubMed1997

Cloning and sequencing of human PEX from a bone cDNA library: evidence for its developmental stage-specific regulation in osteoblasts.

Inactivating mutations of the neutral endopeptidase, PEX, have been identified as the cause of X-linked hypophosphatemia (XLH). Though the function of PEX is unknown, current information suggests that impaired renal phosphate conservation in XLH is due to the failure of PEX to either degrade an undefined phosphaturic factor or activate a novel phosphate-conserving hormone. The physiologically relevant target tissue for the XLH mutation has not been identified. An apparent intrinsic defect of osteoblast function in XLH implicates bone as a possible site of PEX expression. In the current investigation, we employed a polymerase chain reaction (PCR) strategy to amplify a PEX cDNA from a human bone cell cDNA library. We found that the human PEX cDNA encodes a 749 amino acid protein belonging to the type II integral membrane zinc-dependent endopeptidase family. The predicted PEX amino acid sequence shares 96.0% identify to the recently cloned mouse Pex cDNA and has 27-38% identity to other members of the metalloendopeptidase family. Using reverse transcriptase (RT)-PCR with PEX-specific primers, we detected PEX transcripts in both human osteosarcoma-derived MG-63 osteoblasts and in differentiated mouse MC3T3-E1 clonal osteoblasts but not in immature MC3T3-E1 preosteoblasts. The association of impaired mineralization of bone in XLH and the apparent developmental stage-specific expression of PEX in osteoblasts suggest that bone is a physiologically relevant site of PEX expression and that PEX may play an active role in osteoblast-mediated mineralization.

3T3 Cells↗
PubMed1997

The morphologic characteristics of flail mitral leaflets by transesophageal echocardiography.

BACKGROUND AND AIMS OF THE STUDY: Mitral valve prolapse due to floppy mitral valve (MVP/FMV) is a common valvular abnormality with a variable clinical course. Flail mitral valve leaflet resulting in severe mitral regurgitation is a complication of MVP/FMV. METHODS: In order to understand the structural correlates of flail mitral valve leaflet in MVP, we reviewed the morphologic characteristics of the mitral valve by transesophageal echocardiography (TEE) in 72 patients (24 normal; 26 mitral valve prolapse; 22 flail mitral valve leaflet). RESULTS: Compared with the normal group, the mitral valve prolapse group had greater anterior and posterior mitral valve leaflet thickness and anterior mitral valve leaflet length. Patients with flail mitral valve leaflets as a complication of FMV had greater anterior and posterior mitral valve leaflet length and posterior mitral valve leaflet thickness compared with MVP patients without flail mitral valve leaflets. Posterior mitral valve leaflet length was the only echocardiographic independent predictor of flail mitral valve leaflet. Older FMV patients with increased mitral valve leaflet length and thickness are predisposed to flail mitral valve leaflets and severe mitral regurgitation. CONCLUSIONS: TEE may identify patients with MVP/FMV with the greatest structural abnormalities who are at risk for complications such as flail mitral valve leaflet(s).

Adolescent↗
PubMed1996

The accuracy of color Doppler flow imaging for the detection of symptomatic deep venous thrombosis in Chinese patients.

To evaluate the ability of color Doppler flow imaging (CDFI) to detect deep venous thrombosis (DVT), which is difficult to diagnose clinically, 67 limbs of 60 patients who presented with clinical signs strongly indicative of DVT during the period between June 1988 and June 1992, were examined. The iliac, common femoral, and superficial femoral veins were assessed with the patient in the supine position, and the popliteal vein was examined with the patient prone. Gentle but firm compression with the transducer probe was used to test for the presence of DVT. Ascending contrast venograms were also obtained within 24 h after the ultrasound procedure, with venography being used as the standard for comparison with CDFI. DVT was identified in 63 limbs by contrast venography and in 62 limbs by CDFI. The sensitivity and specificity of CDFI were 98.4% and 100%, respectively, while the positive and negative predictive values were 100% and 80%, respectively. The thromboses were classified into three patterns: the filling type, the local type, and mural thrombus, detected in 63%, 27%, and 10%, of the limbs respectively, with the filling type being the most common in this series. The results of our study illustrated that CDFI is highly sensitive and specific for detecting symptomatic DVT and that it should be gradually substituted for venography in such patients.

Adult↗
PubMed1996

Comparison of thickness and distensibility in the carotid artery and descending thoracic aorta: in vivo ultrasound assessment.

Early atherosclerotic changes in the carotid artery and thoracic aorta have been examined by high-frequency ultrasound measuring of intimal-medial thickness and stiffness. Whether changes in stiffness and thickness occur in parallel and whether the determinants of stiffness and thickness in the two vessels are similar is unknown. To examine the relation between ultrasonographic measures of atherosclerosis in the carotid and the thoracic aorta, 146 patients aged 20 to 84 years (mean 54 years) were studied by both transesophageal echocardiography (TEE) and carotid duplex scanning. From two-dimensionally derived M-mode recordings of the thoracic aorta and high-frequency B-mode imaging of the common carotid, the intimal-medial thickness was measured along with diastolic and systolic diameters for calculation of stiffness. Interobserver and intraobserver variability of carotid and aortic intimal-medial thickness and diameter were low. There was a good relation between carotid and aortic intimal-medial thickness (r = 0.69; p=0.0001). Age was the major independent determinant of thickness in both vessels. Carotid and aortic stiffness, as measured by Peterson's elastic modulus, were less closely related (r=0.51; p=0.0001). Age was the only independent predictor of stiffness in both vessels. In conclusion, structural ultrasonographic manifestations of early atherosclerosis in the carotid artery and thoracic aorta are closely related. Large population studies measuring only carotid intimal-medial two-thickness may reflect atherosclerotic changes occurring throughout the vascular bed.

Adult↗
PubMed1996

Spectrum of structural abnormalities in floppy mitral valve echocardiographic evaluation.

Posterior displacement of the mitral valve with billowing into the left atrium has been the major echocardiographic criterion used for the diagnosis of mitral valve prolapse (MVP). However, the current criteria are limited by the influence of hemodynamic factors on the degree of prolapse, whereas complications such as mitral regurgitation, endocarditis, and need for surgery have been associated with redundancy or thickening of the leaflets. Sixty-eight normal subjects (mean age, 40 years; range, 18 to 76 years) were compared with 58 patients with MVP (mean age, 37 years, range, 18 to 83 years). Leaflet displacement across the annular plane in the parasternal long-axis view was mandatory for the diagnosis of MVP. Transthoracic echocardiographic measurements of anterior and posterior leaflet thickness, leaflet length, and chordal length were made from the parasternal long-axis view and the mitral annular diameter, from the apical four-chamber and two-chamber views. The MVP group had greater anterior thickness (4.1 +/- 0.4 mm vs 5.3 +/- 0.7 mm; p = 0.0001), posterior thickness (3.2 +/- 0.4 mm vs 4.7 +/- 0.9 mm; p = 0.0001), anterior length (22.8 +/- 2.0 mm vs 25.7 +/- 1.7 mm; p = 0.0001), posterior length (12.8 +/- 1.0 mm vs 15.7 +/- 2.5 mm; p = 0.0001), chordal length (25.6 +/- 2.7 mm vs 28.0 +/- 2.5 mm; p = 0.0001), and annular diameter (29.1 +/- 1.5 mm vs 31.3 +/- 2.6 mm; p = 0.0001). Of the MVP group, >80% had at least one abnormality identified and >50% had at least two abnormalities. In addition, patients with MVP with significant regurgitation had greater anterior thickness (5.2 +/- 0.7 mm vs 5.8 +/- 0.8 mm; p = 0.015), posterior thickness (4.5 +/- 0.9 mm vs 5.3 +/- 0.7 mm; p = 0.024), posterior length (15.1 +/- 1.6 mm vs 17.9 +/- 4.2 mm; p = 0.004), and annular diameter (36.0 +/- 2.0 mm vs 33.3 +/- 2.1 mm; p = 0.0001). The majority of patients with floppy mitral valves resulting in MVP have structural abnormalities that may be defined by echocardiography. A spectrum of floppy valve structure is demonstrated by echocardiography, with mitral regurgitation occurring more frequently in patients with multiple and more severe anatomic abnormalities. In addition to the presence of prolapse and regurgitation, the assessment of leaflet thickness, leaflet length, annular diameter, and chordal length is fundamental to the definition and stratification of patients with MVP associated with the floppy mitral valve.

Adolescent↗