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G Preston

Publications and source records attributed to G Preston.

At least 19 recordsLinked to original sources
PubMed2000

Expression of p300-truncated fragments results in the modulation of apoptosis in rat mesangial cells.

BACKGROUND: Mesangial cell proliferation, apoptosis, and matrix deposition have pivotal roles in the pathogenesis of renal diseases such as diabetic nephropathy and glomerulonephritis. The behavior of mesangial cells depends on the integration of intracellular signals elicited by hormones and cytokines. We hypothesized that p300 is primarily involved in the integration of signal transduction pathways in rat mesangial cells (RMCs) and that interference with p300 function will alter apoptotic signals. METHODS: We established an RMC cell line expressing the Tet-activator (tTA). RMC-tTA cells were transiently transfected with vectors coding for either the N-terminal third or the C-terminal third of p300. Expression was induced by the addition of doxycycline [Dox; 1 microg/mL; 5% fetal bovine serum (FBS)]. The percentage of apoptosis was determined using the TUNEL technique. Specific protein-protein interactions were determined by Western blot analysis of immunoprecipitated complexes. Cells were treated with 5% FBS or with H2O2 (500 micromol/L, 1 h) with and without Dox. RESULTS: The expression of p300-C resulted in increased susceptibility to low serum-induced (20.0 +/- 4.6 vs. 3.0 +/- 1.7%) and to H2O2-induced apoptosis (75.3 +/- 13.3 vs. 50.8 +/- 6.5%) compared with controls. Immunoprecipitation of p300-C showed an interaction with the transcription factor c-Fos, which was enhanced by H2O2 treatment. Expression of the p300-N resulted in a rescue (34.8 +/- 6. 4 vs. 50.8 +/- 6.5%) from H2O2-induced apoptosis compared with controls. P300-N was shown to form a complex with the transcription factor nuclear factor-kappaB (NF-kappaB). CONCLUSIONS: The data indicate that endogenous p300 is involved in apoptosis in mesangial cells. We propose that interference or enhancement of endogenous p300 function, by expression of exogenous fragments, can alter interactions with c-Fos or NF-kappaB and modulate signals during cellular stress.

Animals↗
PubMed1999

Australia's notifiable diseases status, 1998. Annual report of the National Notifiable Diseases Surveillance System.

In 1998 there were 85,096 notifications to the National Notifiable Diseases Surveillance System; slightly lower than in 1997 (89,579). The number of measles cases remained low, and well below the number reported in the outbreak years of 1993 and 1994. Rubella notifications further decreased and remained low in 1998. The Measles Control Campaign from August to November 1998, did not impact significantly on the number of measles or rubella cases reported for 1998. Notifications of Haemophilus influenzae type b reached a record low since surveillance began in 1991, and appeared to have stabilised at a low rate since the introduction of the conjugated vaccine in 1992. The previously reported outbreak of pertussis in 1997 tapered off in early 1998. Food-borne disease, or detection of disease, appeared to be on the rise with an increase in notification rates of campylobacteriosis and salmonellosis. Notifications of hepatitis A decreased, correcting the previous high number of notifications in 1997. Sexually transmissible diseases (STDs) increased. Notifications for chlamydial infection were the highest for all sexually transmitted diseases and third highest for all notifiable diseases. Notifications of gonococcal infection also continued to rise and have doubled since 1991, whilst notifications for syphilis increased slightly after falling steadily over recent years. Arbovirus infections of concern in 1998 were dengue outbreaks in Far North Queensland and the first case of Japanese Encephalitis for mainland Australia, highlighting the importance of surveillance of arboviruses and vectors for their detection and management.

Australia↗
PubMed1998

Characterization of the hrpC and hrpRS operons of Pseudomonas syringae pathovars syringae, tomato, and glycinea and analysis of the ability of hrpF, hrpG, hrcC, hrpT, and hrpV mutants to elicit the hypersensitive response and disease in plants.

The species Pseudomonas syringae encompasses plant pathogens with differing host specificities and corresponding pathovar designations. P. syringae requires the Hrp (type III protein secretion) system, encoded by a 25-kb cluster of hrp and hrc genes, in order to elicit the hypersensitive response (HR) in nonhosts or to be pathogenic in hosts. DNA sequence analysis of the hrpC and hrpRS operons of P. syringae pv. syringae 61 (brown spot of beans), P. syringae pv. glycinea U1 (bacterial blight of soybeans), and P. syringae pv. tomato DC3000 (bacterial speck of tomatos) revealed that the 13 genes comprising the right half of the hrp cluster (including those in the previously sequenced hrpZ operon) are conserved and identically arranged. The hrpC operon is comprised of hrpF, hrpG, hrcC, hrpT, and hrpV. hrcC encodes a putative outer membrane protein that is conserved in all type III secretion systems. The other four genes appear to be characteristic of group I Hrp systems, such as those possessed by P. syringae and Erwinia amylovora. The predicted products of these four genes in P. syringae pv. syringae 61 are HrpF (8 kDa), HrpG (15.4 kDa), HrpT (7.5 kDa), and HrpV (13.4 kDa). HrpT is a putative outer membrane lipoprotein. HrpF, HrpG, and HrpV are all hydrophilic proteins lacking N-terminal signal peptides. The HrpG, HrcC, HrpT, and HrpV proteins of P. syringae pathovars syringae and tomato (the two most divergent pathovars) had at least 76% amino acid identity with each other, whereas the HrpF proteins of these two pathovars had only 36% amino acid identity. The HrpF proteins of P. syringae pathovars syringae and glycinea also showed significant similarity to the HrpA pilin protein of P. syringae pathovar tomato. Functionally nonpolar mutations were introduced into each of the genes in the hrpC operon of P. syringae pv. syringae 61 by insertion of an nptII cartridge lacking a transcription terminator. The mutants were assayed for their ability to elicit the HR in nonhost tobacco leaves or to multiply and cause disease in host bean leaves. Mutations in hrpF, hrcC, and hrpT abolished or greatly reduced the ability of P. syringae pv. syringae 61 to elicit the HR in tobacco. The hrpG mutant had only weakly reduced HR activity, and the activity of the hrpV mutant was indistinguishable from that of the wild type. Each of the mutations could be complemented, but surprisingly, the hrpV subclone caused a reduction in the HR elicitation ability of the DeltahrpV::nptII mutant. The hrpF and hrcC mutants caused no disease in beans, whereas the hrpG, hrpT, and hrpV mutants had reduced virulence. Similarly, the hrcC mutant grew little in beans, whereas the other mutants grew to intermediate levels in comparison with the wild type. These results indicate that HrpC and HrpF have essential functions in the Hrp system, that HrpG and HrpT contribute quantitatively but are not essential, and that HrpV is a candidate negative regulator of the Hrp system.

Amino Acid Sequence↗
PubMed1998

Negative regulation of hrp genes in Pseudomonas syringae by HrpV.

Mutations in the five hrp and hrc genes in the hrpC operon of the phytopathogen Pseudomonas syringae pv. syringae 61 have different effects on bacterial interactions with host and nonhost plants. The hrcC gene within the hrpC operon encodes an outer membrane component of the Hrp secretion system that is conserved in all type III protein secretion systems and is required for most pathogenic phenotypes and for secretion of the HrpZ harpin to the bacterial milieu. The other four genes (in order), hrpF, hrpG, (hrcC), hrpT, and hrpV, appear to be unique to the group I hrp clusters found in certain phytopathogens (e.g., P. syringae and Erwinia amylovora) and are less well understood. We initiated an examination of their role in Hrp regulation and secretion by determining the effects of functionally nonpolar nptII cartridge insertions in each gene on the production and secretion of HrpZ, as determined by immunoblot analysis of cell fractions. P. syringae pv. syringae 61 hrpF, hrpG, and hrpT mutants were unable to secrete HrpZ, whereas the hrpV mutant overproduced and secreted the protein. This suggested that HrpV is a negative regulator of HrpZ production. Further immunoblot assays showed that the hrpV mutant produced higher levels of proteins encoded by all three of the major hrp operons tested-HrcJ (hrpZ operon), HrcC (hrpC operon), and HrcQB (hrpU operon)-and that constitutive expression of hrpV in trans abolished the production of each of these proteins. To determine the hierarchy of HrpV regulation in the P. syringae pv. syringae 61 positive regulatory cascade, which is composed of HrpRS (proteins homologous with sigma54-dependent promoter-enhancer-binding proteins) and HrpL (alternate sigma factor), we tested the ability of constitutively expressed hrpV to repress the activation of HrcJ production that normally accompanies constitutive expression of hrpL or hrpRS. No repression was observed, indicating that HrpV acts upstream of HrpRS in the cascade. The effect of HrpV levels on transcription of the hrpZ operon was determined by monitoring the levels of beta-glucuronidase produced by a hrpA'::uidA transcriptional fusion plasmid in different P. syringae pv. syringae 61 strains. The hrpV mutant produced higher levels of beta-glucuronidase than the wild type, a hrcU (type III secretion) mutant produced the same level as the wild type, and the strain constitutively expressing hrpV in trans produced low levels equivalent to that of a hrpS mutant. These results suggest that HrpF, HrpG, and HrpT are all components of the type III protein secretion system whereas HrpV is a negative regulator of transcription of the Hrp regulon.

Gene Expression Regulation, Bacterial↗
PubMed1998

The Pseudomonas syringae pv. tomato HrpW protein has domains similar to harpins and pectate lyases and can elicit the plant hypersensitive response and bind to pectate.

The host-specific plant pathogen Pseudomonas syringae elicits the hypersensitive response (HR) in nonhost plants and secretes the HrpZ harpin in culture via the Hrp (type III) secretion system. Previous genetic evidence suggested the existence of another harpin gene in the P. syringae genome. hrpW was found in a region adjacent to the hrp cluster in P. syringae pv. tomato DC3000. hrpW encodes a 42. 9-kDa protein with domains resembling harpins and pectate lyases (Pels), respectively. HrpW has key properties of harpins. It is heat stable and glycine rich, lacks cysteine, is secreted by the Hrp system, and is able to elicit the HR when infiltrated into tobacco leaf tissue. The harpin domain (amino acids 1 to 186) has six glycine-rich repeats of a repeated sequence found in HrpZ, and a purified HrpW harpin domain fragment possessed HR elicitor activity. In contrast, the HrpW Pel domain (amino acids 187 to 425) is similar to Pels from Nectria haematococca, Erwinia carotovora, Erwinia chrysanthemi, and Bacillus subtilis, and a purified Pel domain fragment did not elicit the HR. Neither this fragment nor the full-length HrpW showed Pel activity in A230 assays under a variety of reaction conditions, but the Pel fragment bound to calcium pectate, a major constituent of the plant cell wall. The DNA sequence of the P. syringae pv. syringae B728a hrpW was also determined. The Pel domains of the two predicted HrpW proteins were 85% identical, whereas the harpin domains were only 53% identical. Sequences hybridizing at high stringency with the P. syringae pv. tomato hrpW were found in other P. syringae pathovars, Pseudomonas viridiflava, Ralstonia (Pseudomonas) solanacearum, and Xanthomonas campestris. DeltahrpZ::nptII or hrpW::OmegaSpr P. syringae pv. tomato mutants were little reduced in HR elicitation activity in tobacco, whereas this activity was significantly reduced in a hrpZ hrpW double mutant. These features of hrpW and its product suggest that P. syringae produces multiple harpins and that the target of these proteins is in the plant cell wall.

Bacterial Outer Membrane Proteins↗
PubMed1998

Inhibition of cell proliferation and induction of apoptosis by the retinoid AHPN in human lung carcinoma cells.

In this study, we investigated the effect of the novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN/CD437) on the growth of human lung carcinoma cell lines. AHPN inhibits the proliferation of all cell lines tested, irrespective of the lung tumor type, in a concentration- and time-dependent manner. A dramatic reduction in cell number was observed in adenocarcinoma H460 cells, and was shown to be related to an induction of apoptosis. Bromodeoxyuridine (BrdU) incorporation and flow-cytometric analyses indicated that treatment of H460 cells with AHPN induces cell-cycle arrest at the G1 phase. We therefore investigated the effect of AHPN on several regulatory proteins of the G1 phase of the cell-cycle. The cell-cycle arrest induced by AHPN was accompanied by an inhibition of the hyperphosphorylation of the retinoblastoma (Rb) protein, an indication of G1 arrest. Furthermore, two cyclin-dependent kinases, cdk2 and cdk4, which are normally involved in the phosphorylation of Rb, were shown to have decreased activity. In some cell lines, the decrease in cdk activity may be partly related to an increase in p21(WAF1/Cip1) (p21), an inhibitor of cyclin-dependent kinases. No changes were observed in the cyclin-dependent kinase inhibitor p27(Kip1). The observed increase in p53 in response to AHPN could at least to some extent be responsible for the increased levels of p21. The increase in p53 expression was found to be regulated at a post-transcriptional level. Our results suggest that the growth inhibition of certain lung carcinoma cell lines by AHPN is at least partly related to an increase in p21. However, in other cell lines, different mechanisms appear to be involved. The specificity with which AHPN and other retinoids induce growth arrest and p21 expression indicates that the action of AHPN is not mediated by RAR or RXR receptors, but involves a novel signaling pathway.

Apoptosis↗
PubMed1991

Jugular bulb catheterization does not increase intracranial pressure.

Cerebral venous monitoring through jugular bulb catheterization (JBC) allows assessment of global oxygen delivery adequacy. Because of concern that venous obstruction by catheterization may cause or exacerbate intracranial hypertension, physicians are reluctant to puncture this vessel in brain-injured patients. We evaluated the impact of JBC on intracranial pressure (ICP). 37 consecutive pediatric patients with jugular bulb catheters and ICP monitoring were studied. ICP was monitored in 28 patients during JBC. Also immediately after JBC and daily thereafter the contralateral, ipsilateral, and bilateral jugular veins were compressed in all 37 patients to assess patency of these vessels. Change in ICP was noted. If ICP increased more than 5 torr, compression was stopped. Preinsertion ICP was 17.3 +/- 5.1 and postinsertion 17.2 +/- 5.1 torr. The maximum rise in ICP was 2 torr in a single patient while 6 others had a decrease in ICP. 120 compression tests were performed. Compression ipsilateral to the catheter caused the ICP to rise from 16.0 +/- 4.3 to 18.4 +/- 4.4 torr, and in contralateral compression 15.9 +/- 4.2 to 17.0 +/- 4.4. Neither the duration of catheterization nor the precompression ICP correlated with the rise in ICP. These data revealed no evidence of jugular venous obstruction in the catheterized vessel. We conclude that JBC can be performed in patients without aggravating an elevated ICP.

Adolescent↗
PubMed1990

Jugular bulb catheterization: experience with 123 patients.

Jugular bulb catheterization (JBC) provides cerebral venous access for titration of brain-specific therapy. Little has been written about the catheterization procedure. We prospectively studied the time, number of punctures, success rate, and complications during JBC for a 24-month period in our ICUs. One hundred twenty-three patients (mean age 6.7 yr, range 12 hours to 21 yr) underwent JBC. Procedure time was 15.6 +/- 5.0 (SD) min. Median number of skin punctures was two. All but four were successful on first attempt. Three of the remaining were catheterized on second attempt. Inadvertent carotid puncture occurred in 3%. No other significant complications were noted. Radiography confirmed proper position in 97%. Duration of indwelling venous catheters was 2.5 +/- 1.6 days. All catheters functioned well until removal. We conclude that our technique of JBC is safe and highly successful. It compares favorably with previous, smaller series and with standard anterograde internal jugular catheterization in both children and adults.

Brain↗
PubMed1988

Acute pulmonary edema after near strangulation.

We report a case of acute, noncardiogenic pulmonary edema in an 11-year-old boy who suffered strangulation during an altercation. The clinical presentation was characterized by moderate respiratory distress and hemoptysis. Both the radiographic and clinical findings resolved during the three day admission which followed. A review of the literature is presented, and possible pathogenesis is discussed.

Acute Disease↗
PubMed1985

Reye syndrome and juvenile rheumatoid arthritis in Michigan.

Reye syndrome (RS) is believed to occur infrequently among children receiving long-term aspirin therapy. We reviewed all cases of RS reported to the Michigan Department of Public Health during 1982 and 1983. Three of the 36 patients were receiving aspirin for the treatment of juvenile rheumatoid arthritis. All three patients had clinical courses characteristic of RS and two had supportive histologic findings on liver biopsy. The incidence of RS among children with juvenile rheumatoid arthritis is significantly greater than the incidence of RS among children who do not have juvenile rheumatoid arthritis. These findings support previous studies that showed that the use of aspirin during the antecedent illness may be a risk factor for the development of RS. Physicians should be aware of the potential for the development of RS among children who are receiving long-term aspirin therapy for the treatment of systemic inflammatory illnesses.

Arthritis, Juvenile↗
PubMed1985

Intracranial pressure and cerebral perfusion pressure in near-drowning.

Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were strictly controlled in 11 pediatric victims of near-drowning. Three outcome groups were defined: complete recovery, persistent vegetative state, and death. In the early postimmersion phase (first 72 h), CPP was consistently above 50 mm Hg in all patients. There were occasional, nonrepetitive, and easily controllable ICP spikes above 15 mm Hg in three patients from each group. Repeated ICP spikes above 15 mm Hg were observed in some patients with adverse outcome only after 72 h. Successful control of ICP and CPP did not ensure intact survival, and sustained late intracranial hypertension is more likely a sign of profound neurologic insult rather than its cause.

Brain↗
PubMed1984

Effects of anoxia on cerebral blood flow in the rat brain: evidence for a role of adenosine in autoregulation.

The purpose of these experiments was to determine the utility of a new method for monitoring CBF using a venous outflow technique with an extracorporeal circulation and to examine the effects of agents that potentiate or antagonize the actions of adenosine on the blood flow response to brief periods of anoxia. The results demonstrate the ability of the new technique to detect the increases in CBF in response to anoxia. Caffeine, an adenosine antagonist, reduced the intensity and duration of the anoxia-induced hyperemia. Dipyridamole and papaverine, inhibitors of adenosine uptake, potentiated the increase in CBF during anoxia. The results support the hypothesis that adenosine plays an important role in regulating CBF during anoxic episodes.

Adenosine↗