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Biomedical subjects

R J Jackson

Publications and source records attributed to R J Jackson.

At least 163 records · Page 9Linked to original sources
PubMed1990

Modulation of expression of the hepatitis B virus surface antigen gene by the viral X-gene product.

Human hepatoma cells (HepG2 and HUH7) transfected with a plasmid (pHBV1004) containing the transcription units for the major surface antigen (S) mRNA and the X mRNA of hepatitis B virus (HBV) secreted surface antigen (HBsAg) into the culture medium. A frameshift mutation in the X gene carried by pHBV1004 greatly reduced HBsAg production by cells transfected with an equivalent amount of the mutant (pHBV1004-B). The mutation could be complemented by cotransfection with a plasmid (pSV2HBX) containing the X structural gene under control of the SV40 early promoter. HBsAg production by cells cotransfected with pHBV1004-B and pSV2HBX was equivalent to that in cells transfected with the parent plasmid (pHBV1004) alone. Levels of HBsAg production were directly related to the amount of S mRNA produced, showing that the X-gene product (HBxAg) can modulate expression of the S gene.

Gene Expression↗
PubMed1990

Selection of the 5'-proximal translation initiation site is influenced by mRNA and eIF-2 concentrations.

A cDNA clone of the influenza virus NS (non-structural protein) gene in a vector carrying a bacteriophage T7 RNA polymerase promoter was manipulated so as to reiterate the initiation site to give two in-frame AUG codons 57 nucleotide residues apart. Each initiation site was in either a preferred context (...AUAAUGG...) or a less favourable context (...UUUAUGG...) and the four possible permutations were constructed. When capped mRNA transcripts of these clones were translated in the rabbit reticulocyte lysate system, products from initiation at both AUG codons were observed. At low RNA concentrations the frequency of initiation at the 5'-proximal AUG codon rather than the second was higher when the first AUG codon was in the preferred context, in qualitative agreement with the scanning ribosome model. However, a completely unexpected finding was that the ratio of initiation at the first AUG codon to initiation at the second decreased with increasing mRNA concentration, irrespective of the particular context involved. Several lines of evidence indicated that the increased frequency of initiation at the second AUG codon was not due solely to the lower density of ribosome loading per mRNA at high RNA concentrations, and may therefore be the result of high RNA concentrations out-titring the capacity of endogenous reticulocyte factors responsible for preferential initiation at the 5'-proximal AUG codon. The effect of supplementing the system with purified initiation factors was examined. Only eIF-2 was capable of decreasing the frequency of initiation at the second AUG codon and promoting use of the first AUG at high mRNA concentrations; eIF-3, 4A, 4B, 4C + 4D, 4F and 5 were inactive.

Animals↗
PubMed1990

Initiation of encephalomyocarditis virus RNA translation: the authentic initiation site is not selected by a scanning mechanism.

The authentic initiation site on encephalomyocarditis virus (strain R) RNA is the 11th AUG codon (at nt. 834) from the 5' end of the viral RNA, the downstream of the two AUGs in the sequence....ACGAUGAUAAUAUGGCC... In order to assess the role of ribosome scanning in the selection of the correct initiation site, transcripts of a construct comprising the viral 5' noncoding sequence fused to a reporter gene were translated in vitro and the relative frequency of initiation at these two AUG codons, AUG-10 and AUG-11, was assayed. When deletions from the 5' end were made that retained less than 100 nucleotides of the viral 5'-noncoding sequence, initiation was highly cap-dependent and AUG-10 was utilized in preference to AUG-11, consistent with the scanning ribosome model. On the other hand, when the constructs included the entire 574 nt. segment of the 5' noncoding region situated between the poly(C) tract of the virion RNA and nt. 834, initiation was cap-independent and occurred exclusively at AUG-11, with negligible use of AUG-10. These results suggest that structural features of the 574 nucleotide segment cause initiating ribosomes to bind directly to AUG-11, without scanning the immediate upstream sequences that include AUG-10.

Base Sequence↗
PubMed1990

Selective bowel decontamination results in gram-positive translocation.

UNLABELLED: Colonization by enteric gram-negative bacteria with subsequent translocation is believed to be a major mechanism for infection in the critically ill patient. Selective bowel decontamination (SBD) has been used to control gram-negative infections by eliminating these potentially pathogenic bacteria while preserving anaerobic and other less pathogenic organisms. Infection with gram-positive organisms and anaerobes in two multivisceral transplant patients during SBD led us to investigate the effect of SBD on gut colonization and translocation. METHODS: Twenty-four rats received enteral polymixin E, tobramycin, amphotericin B, and parenteral cefotaxime for 7 days (PTA + CEF); 23 received parenteral cefotaxime alone (CEF), 19 received the enteral antibiotics alone (PTA), 21 controls received no antibiotics. Cecal homogenates, mesenteric lymph node (MLN), liver, and spleen were cultured. RESULTS: Only 8% of the PTA + CEF group had gram-negative bacteria in cecal culture vs 52% CEF, 84% PTA, and 100% in controls. Log Enterococcal colony counts were higher in the PTA + CEF group (8.0 + 0.9) vs controls (5.4 + 0.4) P less than 0.01. Translocation of Enterococcus to the MLN was significantly increased in the PTA + CEF group (67%) vs controls (0%) P less than 0.01. SBD effectively eliminates gram-negative organisms from the gut in the rat model. Overgrowth and translocation of Enterococcus suggests that infection with gram-positive organisms may be a limitation of SBD.

Animals↗
PubMed1990

The novel mechanism of initiation of picornavirus RNA translation.

The initiation of translation of picornaviral RNAs takes place by an unusual mechanism whereby ribosomes bind directly to an internal site rather than scan the RNA from the 5'-end. This internal entry mechanism requires a 450-nucleotide segment of the picornavirus 5'-untranslated region. The ribosome binds initially to a site at the 3'-end of this segment, and then may scan the RNA to reach the authentic initiation site. This novel mechanism may be of relevance to the translation of some cellular mRNAs.

Base Sequence↗
PubMed1990

A crisis of community anxiety and mistrust: the Medfly eradication project in Santa Clara County, California, 1981-82.

Public anxiety of near panic proportions was created by the announcement of a plan to commence aerial application of malathion bait over a large urban area in California for the eradication of the Mediterranean fruit fly within four days. A risk assessment had reported the project entailed no significant risk to health but environmentalist groups and the media ignored the report. We describe the successful measures taken by State health workers to counteract the anxiety which itself constituted a serious public health problem. The most important measure was the rapid convening of a Health Advisory Committee composed of recognized experts and local professionals and leaders to provide an authoritative, respected and sympathetic voice to deal with the community's concerns. These experiences may be of value to other communities facing unwarranted anxiety over perceived environmental hazards.

Animals↗
PubMed1990

Revascularization of a symptomatic pseudoaneurysm of the anterior tibial artery.

Traumatic pseudoaneurysms of the peripheral arterial vasculature occur infrequently. The majority of the experience with these lesions is from this century's wartime experience. Pseudoaneurysms of the tibial vessels comprise only three to seven per cent of all pseudoaneurysms and only seven cases of anterior tibial artery pseudoaneurysms have been reported in the American and British literature since World War II. A high index of suspicion must be maintained for prompt detection of these lesions. Formerly, injuries of the tibial vessels were managed by nonoperative measures or exploration and arterial ligation. These approaches were met with varying results. The evolution of current vascular surgical techniques allows successful reconstruction of these vessels. We wish to report a successful method of repair of symptomatic pseudoaneurysm of the anterior tibial artery using a saphenous vein interposition graft. This technique restored arterial continuity and allowed maximal opportunity for limb salvage. Additional management techniques are discussed and compared in order to improve rapid diagnosis and provide efficient treatment.

Accidents, Occupational↗
PubMed1990

Vitamin A--a pregnancy hazard alert.

Vitamin A is essential to human health, but concerns have arisen recently regarding its potential teratogenicity. Human and animal birth defects have been associated with the use of the vitamin A analogue, isotretinoin, or Accutane, for acne treatment, although the association of such defects with vitamin A itself is unclear. The federal Food and Drug Administration is evaluating the health issues surrounding vitamin A and, together with the manufacturer, has developed restrictions and label warnings to ensure the appropriate use of Accutane. We also have evaluated these issues, with concerns about the possible teratogenicity of high vitamin A intake during pregnancy. Practitioners should be familiar with the possible hazard of excessive dosages of vitamin A and its analogues. Vitamin A daily doses of higher than 8,000 IU for pregnant woman are not necessary for good health and are not recommended. Foods high in beta-carotene can provide the necessary amounts of vitamin A and, in contrast to the synthetic analogues, their use has not been associated with vitamin A toxicity or teratogenicity in humans or animals.

Female↗
PubMed1989

Efficient initiation of mammalian mRNA translation at a CUG codon.

Nucleotide substitutions were made at the initiation codon of an influenza virus NS cDNA clone in a vector carrying the bacteriophage T7 promoter. When capped mRNA transcripts of these constructs were translated in the rabbit reticulocyte lysate, a change in the initiation codon from...AUAAUGG...to...AUACUGG...reduced the in vitro translational efficiency by only 50-60%, and resulted in only a small increase in the yield of short products presumed to be initiated at downstream sites. Synthesis of the full-length product was initiated exclusively at the mutated codon, with negligible use either of in-frame upstream CUG or GUG codons, or of an in-frame downstream GUG codon. We conclude that CUG has the potential to function as an efficient initiation codon in mammalian systems, at least in certain contexts.

Animals↗
PubMed1989

On the fidelity of mRNA translation in the nuclease-treated rabbit reticulocyte lysate system.

As a test of the fidelity of the rabbit reticulocyte lysate system, we have examined the products of translation of various different influenza virus mRNAs, produced by in vitro transcription. A common finding with all mRNA species was that the ratio of full-length translation product to incomplete products decreased with increasing mRNA concentration. These short products are a mixture of (i) polypeptides initiated at the authentic initiation site but terminated prematurely, and (ii) polypeptides initiated at internal sites and terminated at the correct site. Analysis of mRNA stability during the translation assay showed very little degradation, quite insufficient to be the principle cause of incomplete product synthesis. Investigation of the influence of various parameters on the ratio of full-length to incomplete products leads to the conclusion that a high fidelity of translation can be obtained provided certain precautions are followed: the use of capped, rather than uncapped, mRNAs at low concentrations, with KCl concentrations about 20 mM above the level that gives maximum incorporation.

Animals↗
PubMed1989

Cholinesterase activity depression among California agricultural pesticide applicators.

Cholinesterase activity measurements for 542 California agricultural pesticide applicators under medical supervision during the first 9 months of 1985 were analyzed. Twenty-six workers, 4.8% of the sample, had cholinesterase values at or below the California threshold values for removal from continued exposure to cholinesterase-inhibiting pesticides (60% of baseline for red blood cell cholinesterase and 50% of baseline for plasma cholinesterase activity). Eight of these 26 workers, 31.5%, had pesticide-related illnesses. Pesticides most frequently associated with cholinesterase depressions exceeding California threshold values included mevinphos (Phosdrin), oxydemeton methyl (Metasystox-R), methomyl (Lannate), and acephate (Orthene); these pesticides included organophosphates in toxicity categories I and II and one carbamate in toxicity category I.

Agricultural Workers' Diseases↗
PubMed1989

An unusual coordinated cleavage event in the processing of encephalomyocarditis virus polypeptides.

During the translation of encephalomyocarditis virus RNA in the rabbit reticulocyte lysate system, polypeptides 2B and 2C, encoded by the central region of the genome, appear simultaneously in the absence of any detectable 2BC precursor and at a time when translation has advanced into the region coding for polypeptide 3C. This implies the operation of closely coordinated proteolysis at two sites, with at least one cleaved by the virus-coded protease activity 3C.

Cell-Free System↗
PubMed1989

Pesticides and food safety.

This report reviews recent developments regarding the environmental, toxicological, and regulatory issues surrounding pesticide residues in food. Factors affecting the establishment of regulatory limits are discussed. Pesticides monitored by state and federal agencies are compiled and the need for improvements in analytical techniques and enforcement procedures in governmental monitoring programs is pointed out. Specific incidents of concern related to pesticides in food including EDB in grain and grain products, aldicarb in watermelon, demeton-methyl in wine, DDT in fish, S,S,S-tributylphosphorotrithioate in chili peppers, and daminozide in apples and processed apple products are described. The National Academy of Science's study on the Environmental Protection Agency's (EPA) method for setting tolerances for pesticide residues is discussed, especially the dietary cancer risk estimates from pesticides and the inconsistencies in regulating oncogenic pesticides in raw and processed foods existing under the Delaney Clause. The EPA's Tolerance Assessment System is identified to improve the quality of the tolerance establishment process. New California laws to ensure food safety include mandated activities in identifying the toxicological data gaps for pesticides and evaluating pesticide tolerances. Already initiated, tighter regulatory activities at both the federal and the state levels are expected to improve scientific information development, regulatory decisions, and public health protection.

Food Analysis↗
PubMed1989

Health symptoms and occupational exposure to flea control products among California pet handlers.

A statewide telephone survey of health symptoms associated with occupational exposure to flea control products among California pet handlers was conducted in 1987 following several reports of ill workers. The 696 employees interviewed worked at veterinary clinics, pet stores, pet boarding kennels, pet grooming shops, and animal control facilities. Symptom incidence and frequency and flea control product use were reported for the 3 months prior to interview. Eye and skin symptoms and unusual tiredness were elevated among workers who applied flea control products to animals or facilities. After adjustment for potential confounders, these symptoms were elevated 64% to 258% among applicators as compared to nonapplicators who worked in the same facilities. Workers who used protective clothing and equipment and followed some protective work practices were not at increased symptom risk. Some specific flea control active ingredients and application procedures were associated with respiratory effects and with symptoms suggesting systemic pesticide poisoning.

Animals↗
PubMed1989

Protecting agricultural applicators from over-exposure to cholinesterase-inhibiting pesticides: perspectives from the California programme.

California's requirement for medical supervision of applicators regularly handling Toxicity Category I and II organophosphate and carbamate cholinesterase-inhibiting pesticides is examined from a policy perspective by the California Department of Health Services (CDHS). Changes to increase the effectiveness of medical supervision and solutions to a number of practical implementation problems are discussed, including the pesticides which should be monitored, the use of individual cholinesterase baselines, the enzymes to be measured, and the frequency of cholinesterase testing.

Agricultural Workers' Diseases↗
PubMed1989

Agenesis of the gallbladder. A cause of false-positive ultrasonography.

Ultrasonography has evolved into a nonhazardous relatively inexpensive means of diagnosing biliary tract disease. It is considered to have a 95 per cent sensitivity for the diagnosis of cholelithiasis. Occasionally, a small contracted gallbladder associated with stones and chronic cholecystitis will be difficult to visualize with ultrasonography. Two patients with agenesis of the gallbladder were recently treated by the authors. Each patient had ultrasonographic evidence suggestive of a contracted gallbladder with stones. Both patients were explored and found to have absent gallbladders and normal operative cholangiograms. Agenesis of the gallbladder is a rare congenital anomaly with a reported incidence of from 0.01 to 0.04 per cent. Approximately 220 cases have been reported in the literature. Most of these are from necropsy studies. Many of these were newborns with more serious anomalies. One might project an increase in adult cases on the basis of increased usage of ultrasonography in patients with abdominal problems. At the present time, only operative findings including cholangiography can be considered as diagnostic of gallbladder agenesis. However, as more of these cases are reported, preoperative awareness of this entity will be increased.

Adult↗