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Biomedical subjects

J Guo

Publications and source records attributed to J Guo.

At least 235 records · Page 13Linked to original sources
PubMed1998

A surface of Escherichia coli sigma 70 required for promoter function and antitermination by phage lambda Q protein.

The sigma initiation factor sigma70 of Escherichia coli acts not only in promoter recognition and DNA strand opening, but also to mediate the transformation of RNA polymerase (RNAP) to an antiterminating form by the phage lambda gene Q protein. Q is able to bind and modify RNAP when alpha70, still present in the initially elongating enzyme, recognizes a repeat of the -10 promoter element and induces a transcription pause. We have isolated mutations in the rpoD gene for sigma70 that impair Q function because they reduce the ability of sigma70 to recognize the downstream pause site. These mutations identify a locus of sigma70 that is important for the formation and stability of open promoter complex, likely because it mediates protein interactions with RNAP core.

Amino Acid Substitution↗
PubMed1998

[Effect of zinc on the cellular immunity and NK cell activity in acute heat exposed rats].

To study the effects of zinc on the cellular immunity and NK cell activity in acute heat-exposed rats. Rats were fed with dietary containing high, moderate and low zinc for 15 days. The concentrations of zinc in high, moderate and low zinc dietary are 92.20 mg/kg, 45.61 mg/kg and 21.70 mg/kg respectively. After exposed to acute heat (41.5 degrees C) for 5 min, 30 min and 60 min, the rats were killed and the cellular immunity and NK cell activity were measured. The proliferation of lymphocyte and the NK cell activity were higher in high zinc group than in moderate and low zinc groups no matter the rats were exposed to heat or not. Zinc can improve the cellular immunity and NK cell activity in acute heat exposed rats.

Animals↗
PubMed1998

[Effects of different zinc level diets and heat exposure on the contents of Zn, Cu and Fe in brains of rats].

Forty-eight SD male rats were randomly divided into group A, B and C. Rats in each group were also divided into 2 parts. One part was used for heat exposure and the other was used for room temperature control. On the basis of AIN-93 m diet composition, group A, B and C zinc diets were prepared by adding or reducing zinc carbonate. Zinc contents of group A, B and C zinc diet per kilogram were 92.2 mg, 45.61 mg and 21.70 mg respectively. 14 days later the rats were exposed to high temperature (Tdb 40 degrees C, Twb 30.8 degrees C) for 3 hours. The Contents of Zn, Cu and Fe in hippocampus, cerebral cortex and cerebellum of rats were determined by atomic absorption spectrophotometer. The results revealed that 1. hyperthermal exposure could increase Cu content in rat hippocampus significantly, 2. after heat exposure, Cu content in hippocampus was higher than in cerebral cortex and cerebellum. Cu contents in cerebellum of room temperature control rat were higher than cerebral cortex and hippocampus, 3. intakes of different zinc level diets chiefly influenced content of Cu rat cerebellum and slightly affected iron content in it, 4. high, middle level zinc diet intake could reduce Cu content in heat-stressed rat cerebellum.

Animals↗
PubMed1998

Expression of constitutively activated Gialpha2 in vivo ameliorates streptozotocin-induced diabetes.

Streptozotocin treatment in vivo generates a model of insulin-dependent diabetes mellitus via destruction of the pancreatic beta-cells responsible for insulin secretion. Tissue-specific expression of the Q205L constitutively activated mutant form of the G-protein Gialpha2 in vivo ameliorates streptozotocin-induced insulin-dependent diabetes mellitus in transgenic mice. Conditional expression of Q205L Gialpha2 in vivo in liver, skeletal muscle, and adipose tissue markedly rectifies glucose tolerance, fasting glucose levels, and glycogen synthase activation in the mice with insulin-dependent diabetes mellitus, providing a novel therapeutic target for diabetes.

Adipose Tissue↗
PubMed1998

Alteration of capsaicin and endotoxin-induced calcitonin gene-related peptide release from mesenteric arterial bed and spinal cord slice in 18-month-old rats.

In the present study, we investigated the changes in capsaicin- and endotoxin-induced calcitonin gene-related peptide (CGRP) release from mesenteric arterial bed (MAB) and spinal cord slices (SCS) in 2-month-old and 18-month-old Wistar rats. The isolated MAB or SCS was perfused or incubated in vitro. The CGRP-like immunoreactivity in perfusate or supernatant was measured by radioimmunoassay. The results showed that endotoxin triggered CGRP release from isolated rat MAB and SCS, which represent the peripheral and central terminals of CGRP-containing sensory nerves, respectively. Either basal or stimulated CGRP release induced by capsaicin and endotoxin was significantly decreased as the rats aged from 2 to 18 months. The basal CGRP release was 14.9 +/- 1.8 and 5.8 +/- 1.0 pg/ml from MAB and 3.50 +/- 0.54 and 1.78 +/- 0.16 pg/ml/mg from SCS in 2-month-old and 18-month-old rats, respectively. The release of CGRP evoked by capsaicin (10(-7) mol/L) and endotoxin (1 to approximately 5 microg/ml) from MAB and SCS was significantly decreased by more than 50% in 18-month-old rats. These data suggest that both the basal and capsaicin- or endotoxin-stimulated CGRP release from MAB and SCS display a significant decrement in aged rats that may have some physiological, pathological, and behavioural relevance in age-related diseases.

Aging↗
PubMed1998

Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.

The ligand for osteoprotegerin has been identified, and it is a TNF-related cytokine that replaces the requirement for stromal cells, vitamin D3, and glucocorticoids in the coculture model of in vitro osteoclastogenesis. OPG ligand (OPGL) binds to a unique hematopoeitic progenitor cell that is committed to the osteoclast lineage and stimulates the rapid induction of genes that typify osteoclast development. OPGL directly activates isolated mature osteoclasts in vitro, and short-term administration into normal adult mice results in osteoclast activation associated with systemic hypercalcemia. These data suggest that OPGL is an osteoclast differentiation and activation factor. The effects of OPGL are blocked in vitro and in vivo by OPG, suggesting that OPGL and OPG are key extracellular regulators of osteoclast development.

Amino Acid Sequence↗
PubMed1998

Normal brain myelination in a patient homozygous for a mutation that encodes a severely truncated methionine adenosyltransferase I/III.

Two isozymes of mammalian methionine adenosyltransferase, MAT I and MAT III, are expressed solely in adult liver. They are, respectively, tetramers and dimers of a single subunit encoded by the gene MAT1A. A third isozyme, MAT II, contains a catalytic subunit encoded by a separate gene, MAT2A, and is expressed in a variety of tissues, including (to a slight extent) adult liver. Based on a recent finding that 2 children with isolated hypermethioninemia and brain demyelination were homozygous for MAT1A mutations predicted to produce severely truncated proteins, and devoid of activity when expressed, it was concluded that complete lack of MAT I/III activity may be associated with neurological symptoms and demyelination. We now report that a 43-year-old man with persistent isolated hypermethioninemia, previously demonstrated to have deficient MAT activity in his liver, has normal brain myelination on MRI and normal neurological function, despite being homozygous for a 539 TG insertion in exon V of MAT1A, so that the gene is predicted to encode a protein of only 184 rather than the normal 395 amino acids. This patient's exon V mutation was demonstrated by SSCP analysis and verified by sequencing. Both parents are heterozygous for the same insertion. This suggests that MAT1A mutations producing severely truncated proteins do not necessarily produce brain demyelination. This finding has relevance to a previously reported 4-year-old girl who was also homozygous for the 539insTG mutation. Finally, our patient's 7% residual hepatic MAT activity, measured at 1 mM methionine, may reflect the hepatic activity of the more ubiquitous enzyme form, MAT II.

Adult↗
PubMed1998

TNF-induced enterocyte apoptosis in mice is mediated by the TNF receptor 1 and does not require p53.

Injection of recombinant mouse TNF into mice is known to induce a shrinkage of the duodenal villi, which becomes evident 30-90 min later and is associated with a detachment of enterocytes in the lumen. These cells can be collected by lavage and are all apoptotic, i.e. hypodiploid as seen by flow cytometric analysis. Thus the count of detached cells was used as an evaluation of the TNF-induced cell loss and apoptosis in the mucosa. TNF injection induced a cell loss of similar magnitude in wild-type (+/+) or in mice lacking the TNF receptor (TNFR)2 (p75, TNFR2-/-), while mice lacking the TNFR1 (p55, TNFR1-/-) were completely resistant to this effect. TNF increased the expression of p53 tumor suppressor gene in the enterocytes from the crypts but not from the villi, as seen by Western blots and histochemistry. TNF increased the expression of p53 in both TNFR2-/- and TNFR1-/- mice. Furthermore, enterocyte cell loss was not attenuated in p53-/- mice. The results indicate that TNF, acting on its receptor 1, induces an apoptotic detachment of the enterocytes from the tip of the villi (i.e. the old enterocytes), while in the enterocytes from the crypts (the young enterocytes) TNF increases, via either TNFR1 or TNFR2, the expression of p53, without inducing apoptosis.

Animals↗
PubMed1998

Inhibition of 11beta-hydroxysteroid dehydrogenase by bioflavonoids and their interaction with furosemide and gossypol.

Inhibition of 11beta-hydroxysteroid dehydrogenase (11beta-OHSD) can cause a mineralocorticoid effect. This enzyme, in guinea pig renal cortex microsomes in vitro, is inhibited by quercetin, tea polyphenols, furosemide, and gossypol. The dietary polyphenols, quercetin and tea polyphenols, interact with furosemide to enhance its 11beta-OHSD inhibitory effect. Tea polyphenols added to the effect of gossypol. We conclude that the diet contains inhibitors of 11beta-OHSD that can alter the activity of this enzyme and may modify the degree of endogenous mineralocorticoid activity.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1998

Clinical results of the midstem porous-coated anatomic uncemented femoral stem in primary total hip arthroplasty: a five- to nine-year prospective study.

The clinical and radiologic results of an inclusive series of 60 patients (70 hips) who had primary total hip arthroplasty using the porous-coated anatomic (PCA) midstem femoral prosthesis was prospectively studied. The midstem component features a proximal circumferential porous bead coating similar to the PCA primary stem; but increased proximal thickness, increased length, and a distal anterior curve for additional rotational stability. The mean Harris Hip Score rose from 39.5 points before surgery to 91.3 points at a minimum follow-up of 5 years (average, 69 months); 88% were good or excellent. Moderate or severe thigh pain on a visual analogue scale was reported by 30% of cases, and was more common in women. Radiographic analysis indicated preservation of proximal bone stock and bony ingrowth in 87%, but stem subsidence in 9%. One stem has been revised for subsidence and thigh pain (1.4%), and one stem is radiographically loose, but the patient refuses surgical revision. Endosteal osteolysis was rarely seen (2.8%) and was benign in appearance. Acetabular components used included 63 nonmodular PCA metal-backed cups and 7 hemispherical porous ingrowth cups fixed with screws. One PCA cup was revised for loosening (1.4%), and one is radiographically loose but stable (1.4%). Only one cup exhibited an area of osteolysis. At this intermediate follow-up the clinical outcome of the midstem component is stable and excellent. The radiographic results appear superior to the PCA primary stem, with a lower incidence of stem subsidence and osteolysis. The prevalence of thigh pain is a concern and we recommend regular follow-up of patients with the midstem femoral implant, and the use of a visual analogue thigh pain scale when any femoral prosthesis is evaluated.

Arthroplasty, Replacement, Hip↗
PubMed1998

Blood transfusion strategies for total knee arthroplasty: minimizing autologous blood wastage, risk of homologous blood transfusion, and transfusion cost.

In this nonrandomized study, alternative strategies were suggested to 10 orthopaedic surgeons to minimize autologous blood wastage, the risk of homologous blood transfusion, and cost associated with blood product usage after total knee arthroplasty (TKA). One hundred fifty-five patients with 177 consecutive TKAs over a 2-year period were studied. Group 1 patients had undergone unilateral TKA and did not predonate; 1A patients (n = 19) were drained with a Hemovac, and 1B patients (n = 28) with a postoperative blood recovery system. Group 2 patients (n = 47) predonated one packed red blood cell (pRBC) unit. Group 3 patients (n = 20) predonated 2 pRBC units. Group 4 patients had undergone bilateral sequential TKAs (n = 21) and had predonated 2 pRBC units. Group 5 patients (n = 14) had undergone revision TKA procedures and their blood requirements were individualized. Group 6 patients (n = 6) had preexisting anemia and were excluded from the study. There was no significant difference in total blood loss (909 mL) between groups. Female sex was associated with significantly lower admission hematocrit. Homologous blood was required for 4% of patients in the entire study and the percentage was not statistically different between groups. Twenty-five percent of patients who predonated autologous pRBCs did not use all or some of it. In group 1, the postoperative blood recovery system had a significant effect on reducing postoperative hematocrit drop (P = .0001), but it was not a significant factor if autologous pRBCs were available. The costs associated with group 1A were significantly less (P = .0001) compared with the other groups; group 1A had the highest admission hematocrit (43.2). Transfusion with autologous pRBCs was related to lower admission hematocrit rather than to increased postoperative blood loss. An algorithm is presented to provide cost-effective management of blood products after TKA.

Aged↗
PubMed1998

Deregulation of cell growth by the K1 gene of Kaposi's sarcoma-associated herpesvirus.

At a position equivalent to the gene encoding the saimiri transforming protein (STP) of herpesvirus saimiri (HVS), Kaposi's sarcoma-associated herpesvirus (KSHV) contains a distinct open reading frame called K1. Although KSHV and HVS are related members of the rhadinovirus subgroup of gamma herpesviruses, K1 and STP exhibit no similarity in amino acid sequence or in structural organization. Since STP is required for the oncogenic potential of HVS, we investigated the functional consequence of K1 expression. Expression of the K1 gene in rodent fibroblasts produced morphologic changes and focus formation indicative of transformation. A recombinant herpesvirus in which the STP oncogene of HVS was replaced with K1, immortalized primary T lymphocytes to IL-2 independent growth and induced lymphoma in common marmosets. These results demonstrate the transforming potential of the K1 gene of KSHV.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Stimulation of thrombocytopoiesis decreases platelet beta2 but not beta1 or beta3 integrins.

The expression of CD29, CD61, CD18 and CD11a on platelets was examined by flow cytometry in mice treated with leukaemia inhibitory factor (LIF) or megakaryocyte growth and development factor (PEG-rHuMGDF or mpl-ligand). Treatment for 7-14 d with PEG-rHuMGDF or LIF increased the number of platelets in peripheral blood from 0.9 up to <2.0 x 10(6)/microl. These treatments decreased the expression of CD11a and CD18, whereas that of CD29 or CD61 was not markedly changed. Study after various doses or times of PEG-rHuMGDF administration indicated that a decrease of CD18 expression occurred when platelet counts started to rise. Platelet RNA content was increased in mice treated with PEG-rHuMGDF but double staining indicated that expression of CD18 was not correlated with RNA content. To evaluate integrin expression as a function of time in circulation, platelets were biotinylated in vivo. In normal or PEG-rHuMGDF-treated mice, the expression of CD29 or CD61 did not change, whereas that of CD18 decreased significantly as a function of time in circulation. These findings indicate, firstly, that stimulation of thrombocytopoiesis leads to the release of platelets with a low content of beta2 integrin and, secondly, that this integrin is also selectively lost while in the circulation.

Animals↗
PubMed1998

Expression of p210 and p190 BCR-ABL due to alternative splicing in chronic myelogenous leukaemia.

The hallmark of chronic myelogenous leukaemia (CML) is the presence of the Philadelphia chromosome and its resultant fusion message, BCR-ABL, and fusion protein, p210. Patients with CML in blast crisis, or with Philadelphia positive acute lymphoblastic leukaemia (ALL), can have a smaller BCR-ABL fusion transcript possessing only the first exon of BCR fused to ABL. This smaller transcript encodes a 190 kD protein which is more strongly transforming than the p210 protein derived from the larger CML-associated transcript. We performed RT-PCR on samples from CML patients in chronic phase to determine the frequency and mechanism of p190 and p210 co-expression and to see if this correlated with clinical indices. We examined the peripheral blood or marrow of 67 patients with CML and found that 35 of them expressed both transcripts whereas the remainder expressed the p210-encoding transcript exclusively. Additional PCR products of an intermediate size were also frequently detected and have been isolated and sequenced. Data from two of these products indicate that they are the result of alternative splicing and include variable combinations of BCR exons. We believe that the expression of the p190-encoding transcript in the chronic phase of CML is also due to alternative splicing. A comparison of patients co-expressing the p190- and p210-encoding transcripts with those patients who expressed only the p210-encoding transcript detected significantly higher white blood cell (WBC) counts and blast cell counts at time of testing as well as significantly higher white blood cell counts at diagnosis.

Adolescent↗
PubMed1998

Relationship between autoantibody epitopic recognition and immunoglobulin gene usage.

An immunodominant region recognized by serum autoantibodies has been defined on the autoantigen thyroid peroxidase (TPO) using recombinant human TPO-specific Fab or a panel of mouse MoAbs. We have now analysed the epitopic relationships between the four recombinant Fab that identify the A and B domains of the TPO immunodominant region and (i) the mouse TPO MoAb as well as (ii) nine new TPO-specific Fab isolated independently. Competition between mouse MoAbs and recombinant Fab for binding to 125I-TPO revealed three patterns. First, for MoAbs 15, 59, 64 and 18, TPO binding was virtually abolished (approximately 90%) by Fab which define the A domain of TPO, with less inhibition by B domain Fab. Second, for MoAbs 2, 9 and 47, the Fab competed much less for TPO binding, and, when detectable, inhibition was predominantly with B domain Fab (65-20%). Third, for MoAbs 53, 30, 1, 24 and 40, none of the Fab competed effectively for 125I-TPO binding. Thus, the epitopes for MoAbs 18, 59, 64 and 15 correspond to those of the A domain defined by the human Fab, and the epitopes for MoAbs 2, 9 and 47 correspond to those of the B domain. In the second part of the study, competition studies demonstrated that the epitopes of nine new Fab corresponded to those of the four Fab that define the immunodominant region. For four new Fab, TPO binding was inhibited to a greater extent by B- than by A-domain Fab (65-95% versus <50%). In contrast, for five new Fab the A-domain Fab were more effective inhibitors (approximately 90%) than the B-domain Fab. In addition, consistent with previous observations, all five new Fab with 02/012 kappa L chains, but none of the new Fab with non-O2/O121 chains, interacted with A-domain epitopes. In conclusion, we have established the epitopic relationships between recombinant human Fab and mouse MoAbs that define the TPO immunodominant region on TPO. Further, analysis of recombinant TPO Fab isolated from patients on three continents strengthens the paradigm of a relationship between autoantibody epitopic recognition and immunoglobulin gene usage.

Animals↗
PubMed1998

Role of mast cells and monoamines in the thrombocytopaenia and mortality elicited by tumour necrosis factor in mice.

We explored the thrombocytopaenia elicited by the i.v. injection of mouse recombinant tumour necrosis factor (TNF) in mice. Injection of 10 micrograms of TNF led to a thrombocytopaenia (evident after 0.5 hr) which was caused by decreased platelet survival, as seen by the injection of labelled platelets. TNF-induced thrombocytopaenia was not prevented by heparin, nor by depletion of either fibrinogen or C'. TNF-induced thrombocytopaenia was markedly attenuated in mice treated with reserpine, an agent that depletes monoamines from mast cells and other cells, and in the mast-cell-deficient WWv mice. In vitro, TNF elicited a modest release of monoamine from peritoneal mast cells and from a mast cell line. When mice are injected with 3H-serotonin (3H-5HT) before TNF, TNF injection increased the plasma 3H-5HT content 1 hr later, modifications absent in reserpine pretreated or mast-cell-deficient mice. 3H-5HT content of the small intestine was markedly depleted in TNF-injected mice, suggesting that this organ is the source of the plasma 3H-5HT. Drop in body temperature and mortality induced by TNF were also attenuated in mast-cell-deficient, and in reserpine pretreated mice. These results indicate that TNF can induce a release of monoamines from mast cells, mainly from those of the small intestine, a process that contributes to TNF-induced thrombocytopaenia and mortality.

Adrenergic Uptake Inhibitors↗
PubMed1998

Glycated albumin stimulates fibronectin gene expression in glomerular mesangial cells: involvement of the transforming growth factor-beta system.

Albumin modified by Amadori glucose adducts, formed in increased amounts in diabetes, stimulates collagen IV production and gene expression in renal glomerular mesangial cells, and induces mesangial matrix accumulation accompanied by increased mRNA encoding alpha 1 (IV) collagen and fibronectin in diabetic animals. These effects contribute to the pathogenesis of diabetic nephropathy, and resemble biologic activities of the cytokine TGF-beta 1, which also has been causally implicated in diabetic renal disease. We postulated that Amadori-modified glycated albumin modulates TGF-beta 1 expression in mesangial cells, and that TGF-beta 1 participates in mediating the glycated albumin-induced increases in mesangial cell matrix production. To test this hypothesis, we measured mRNA encoding TGF-beta 1, the TGF-beta Type II receptor and fibronectin, a key matrix component of the TGF-beta 1 tissue response, after incubation of mesangial cells with glycated albumin. Steady state levels of the mRNAs encoding for these proteins were stimulated when mesangial cells were cultured in the presence of albumin containing Amadori glucose adducts compared with levels in cells cultured with the nonglycated, glucose-free counterpart. The glycated protein-induced changes in mRNA expression were observed with concentrations of glycated albumin encompassing those found in clinical specimens and in media containing physiologic (5.5 mM) glucose concentrations, indicating that they were due to the glucose-modified protein and not to a hyperglycemic milieu. Further, they were accompanied by increased translated fibronectin protein, which was prevented with TGF-beta neutralizing antibody, as was the glycated albumin-induced increase in fibronectin mRNA. The findings indicate that Amadori-modified glycated albumin stimulates mesangial cell TGF-beta 1 gene expression by mechanisms that are operative under normoglycemic conditions. These data provide the first link between elevated glycated serum albumin concentrations and increased TGF-beta 1 bioactivity in the pathogenesis of mesangial matrix accumulation in diabetes.

Animals↗