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Biomedical subjects

M E Jackson

Publications and source records attributed to M E Jackson.

At least 55 records · Page 3Linked to original sources
PubMed1991

Coexistence of reduced function of natural killer cells and osteoclasts in two distinct osteopetrotic mutations in the rat.

Recent evidence suggesting that immune cells and their products (cytokines) play an important role in the regulation of skeletal development and function, particularly of the osteoclast, implies that immune cell dysfunction may be involved in the pathogenesis of certain skeletal disorders. The mammalian osteopetroses are a pathogenetically heterogeneous group of skeletal disorders characterized by skeletal sclerosis resulting from reduced osteoclast-mediated bone resorption. Using a 51Cr-release microcytotoxicity assay we demonstrated that splenic natural killer (NK) cell activity was significantly reduced in two distinctly different osteopetrotic mutations in the rat, osteopetrosis (op) and toothless (tl). To determine whether this reduction in NK cell-mediated cytotoxicity is caused by decreased cell number and/or function in these osteopetrotic mutants, we quantitated NK cells by analyzing mononuclear cell suspensions labeled for two-color fluorescence with OX8 and OX19 monoclonal antibodies in a fluorescence-activated cell sorter. Flow cytometry of these double-labeled cells revealed that the percentage of NK cells (OX8+/OX19- subset) in op and tl spleens was not significantly different from that of normal spleens. These results suggest that NK cells in these osteopetrotic mutants are functionally defective. Thus aberrations in osteoclast and NK cell function coexist in these mutations, and their developmental relationships deserve further study.

Animals↗
PubMed1991

The B subgroup bovine papillomaviruses lack an identifiable E6 open reading frame.

Analysis of the corrected DNA sequence for the bovine papillomavirus type 4 (BPV4) genome revealed that there is no open reading frame (ORF) that might encode an E6 protein. The other two B subgroup bovine papillomaviruses, BPV3 and BPV6, were found to have the same arrangement of ORFs in this region as BPV4. Thus, we conclude that E6 functions are either not required by these viruses or are performed by another viral (or host) protein. Furthermore, the position that might be expected to be occupied by E6, between the long control region and the E7 ORF, contains the E8 ORF, which has the potential to encode a 42-residue polypeptide with considerable similarity to the E5 transforming protein of BPV1. Therefore, it appears that during the evolution of the B subgroup of BPVs, genomic rearrangements may have occurred resulting in the present layout of the early ORFs.

Amino Acid Sequence↗
PubMed1991

Positive and negative E2-independent regulatory elements in the long control region of bovine papillomavirus type 4.

The long control region (LCR) of bovine papilloma-virus type 4 demonstrated enhancer activity when cloned upstream of a bacterial chloramphenicol acetyltransferase reporter gene under thymidine kinase promoter control. Deletion analysis of the LCR revealed the presence of several positive and negative control elements, all of which could function independently of the viral E2 trans-activator. Each of the three positive elements present appeared to be paired with a negative element which modulated its activity. DNase I footprinting was used to identify protein binding sites within the LCR, which might represent these control elements. The results suggest a highly complex and finely tuned control of viral gene expression.

Animals↗
PubMed1990

Cooperation between bovine papillomavirus type 4 and ras in the morphological transformation of primary bovine fibroblasts.

Primary bovine fibroblasts derived from foetal palate can be transformed by bovine papillomavirus type 4 DNA only in the presence of an activated ras gene, indicating that the virus does not encode all the information required for morphological transformation of non-established cells. A subgenomic fragment containing the complete E8 and E7 open reading frames (ORFs) induces transformation in cooperation with activated ras but transformation is abolished when the E7 ORF is deleted at the 3' end, showing that this ORF encodes a necessary transforming function. Transformation is more aggressive when the E8 and E7 ORFs are placed under the transcriptional control of the long terminal repeat of the mouse Moloney leukaemia virus, suggesting that the degree of transformation is dependent on the level of expression of these genes.

Amino Acid Sequence↗
PubMed1989

Risk of functional decline among well elders.

Active lifestyles may delay the onset of the functional consequences of chronic disease, potentially increasing active life expectancy. We analyzed the Longitudinal Study of Aging (LSOA) to test the hypothesis that elders participation in an active lifestyle prevents loss of function. Focusing on the cohort aged 70-74 who reported being able to carry 25 lb, walk 1/4 mile, climb 10 steps and do heavy housework without help and without difficulty at baseline, decline was defined as no longer being able to perform these tasks independently and without difficulty 2 years later. Using multivariate logistic regression, results reveal that those who did not report regularly exercising or walking a mile were 1.5 times more likely to decline than those who did, controlling for reported medical conditions and demographic factors. Similar findings (with different models) were observed for both men and women. Findings suggest the potential value of programs oriented toward the primary prevention of functional decline.

Aged↗
PubMed1988

Analysis of the membrane-binding domain of penicillin-binding protein 5 of Escherichia coli.

Internal deletions close to the C-terminus of the Escherichia coli penicillin binding protein 5 (PBP5, DacA) have defined the C-terminal 18 residues of the protein as essential for membrane binding. This C-terminal sequence is capable of forming a strongly amphiphilic alpha-helix. In this paper we show that the PBP5 amphiphilic helix is able to anchor the periplasmic TEM-beta-lactamase to the inner membrane. In addition, we have demonstrated that mature PBP5 (lacking the N-terminal signal sequence) possesses the ability to bind to the membrane from a soluble form of the protein, showing that translocation across the membrane is unnecessary for anchoring to be established.

Amino Acid Sequence↗
PubMed1987

An 18 amino acid amphiphilic helix forms the membrane-anchoring domain of the Escherichia coli penicillin-binding protein 5.

Small (10 residue) C-terminal deletions of PBP5 cause release of this inner membrane protein into the periplasm, indicating disruption of the membrane binding domain. To define the extent of the membrane anchoring domain, oligonucleotide-directed mutagenesis was used to introduce both single amino acid changes and novel restriction sites into the DNA, allowing subsequent construction of precise internal deletions. The 10 C-terminal amino acid residues possess very weak membrane anchoring potential. By extending the sequence to 18 residues membrane binding equivalent to that of authentic PBP5 was achieved. A proline substitution in this region, breaking a potential alpha-helix, also disrupts the membrane binding domain. These results are discussed with respect to the amphiphilicity of the C-terminal sequence when arranged in an alpha-helix.

Amino Acid Sequence↗
PubMed1987

Effect of cage level (tier) on the performance of White Leghorn chickens.

Conflicting reports exist in the literature about the effects of cage level (tier) on laying hen performance. Results clearly indicate, under conditions of this study, that performance as measured by egg production, egg weight, and mortality significantly deteriorated in a linear fashion progressing from the bottom to the top in three and four tier cages. Causes may be related to fear associated with differences in light intensity or differences in exposure to visual stimuli between the tiers.

Animals↗
PubMed1987

Shell quality: potential for improvement by dietary means and relationship with egg size.

Three experiments were conducted by sampling a total of 15,705 eggs from Leghorn hens fed diets varying in methionine, Na, and Ca content. In Experiment 1, birds of four different ages were housed in a common environment and fed diets containing between .233 and .383% methionine. In Experiment 2, birds of five different ages were housed in a common environment and fed diets containing .15, .30, and .45% Na and .25, .45, and .65% nonphytate phosphorus (NPP). In Experiment 3, eggs were sampled from 42 to 62 wk of age in 4-wk intervals from hens fed diets containing from 3 to 9% Ca in increments of 1.5%. Feeding lower levels of methionine (.233%) produced significantly lower egg weights and greater shell strength but at the expense of a decline in egg production at early ages. Reducing the NPP level from .65 to .25% produced lower egg weights and greater shell strength. A corresponding drop in production was not observed except at the .45%-Na level. No significant effects of Na on shell strength were observed. Higher Ca levels produced greater shell strength and had variable effects on egg weight. Increasing the Ca level beyond 6% resulted in a significant decline in production. Regression analyses indicated that within a population, the relationship between egg weight and shell strength is positive. In some instances, the relationship was curvilinear, where the positive association between egg weight and shell strength decreased with increasing egg weights.

Animals↗
PubMed1986

Intermediates in the assembly of the TonA polypeptide into the outer membrane of Escherichia coli K12.

The tonA gene of Escherichia coli K12 was cloned into a multicopy plasmid, leading to substantial overproduction of the corresponding 78,000 Mr polypeptide in the outer membrane. The approximate size of the tonA gene and its direction of transcription were established by Tn1000 mutagenesis. A family of tonA deletions was constructed in vitro by Bal31 exonuclease digestion, followed by splicing of an "oligo stop" sequence to each 3' terminus in order to ensure prompt termination of translation of the truncated polypeptides in vivo. All these polypeptides proved to be extremely unstable in exponentially growing cultures but were relatively stable in maxicells. Under these conditions the truncated polypeptides, unlike wild-type TonA, fractionated with the Sarkosyl-soluble fraction of the cell envelope, indicating that these proteins are blocked in assembly as inner membrane (translocation) intermediates or as outer membrane (maturation) intermediates unable to form Sarkosyl-resistant complexes. We have also examined the kinetics of assembly of wild-type TonA into the outer membrane and the results indicate that, following cleavage of the N-terminal signal peptide, the protein passes through an apparently membrane-free intermediate form and only appears in the outer membrane after a delay of at least 50 seconds, following the completion of synthesis. From these results, we propose that the assembly of TonA involves translocation (with concomitant cleavage of the signal sequence) directly into the periplasm, followed by partitioning into the outer membrane. We further propose that the C terminus of TonA is essential for final maturation in the outer membrane in Sarkosyl-resistant form but that the C-terminal half of the molecule probably does not contain any topogenic sequences required for partitioning to the outer membrane.

Bacterial Outer Membrane Proteins↗
PubMed1986

The C terminus of penicillin-binding protein 5 is essential for localisation to the E. coli inner membrane.

Penicillin-binding protein 5 (PBP5) has been previously identified as a component of the inner membrane of Escherichia coli and we present here further evidence that PBP5 is tightly bound to the membrane. To investigate the regions of PBP5 involved in membrane binding we have constructed a series of C-terminal deletions and shown that the removal of as few as 10 amino acids results in the release of the truncated protein into the periplasm. The C terminus, therefore, appears to be important for interaction with the membrane; however, inspection of the amino acid sequence does not reveal extended runs of hydrophobicity typical of a membrane anchor. Thus we conclude that PBP5 is anchored to the inner membrane by a mechanism not previously described.

Amino Acid Sequence↗
PubMed1985

An inner membrane protein N-terminal signal sequence is able to promote efficient localisation of an outer membrane protein in Escherichia coli.

To test the importance of N-terminal pre-sequences in translocation of different classes of membrane proteins, we exchanged the normal signal sequence of an Escherichia coli outer membrane protein, OmpF, for the pre-sequence of the inner membrane protein, DacA. The DacA-OmpF hybrid was efficiently assembled into the outer membrane in a functionally active form. Thus the pre-sequence of DacA, despite its relatively low hydrophobicity compared with that of OmpF, contains all the essential information necessary to initiate the translocation of OmpF to the outer membrane. Since processing of DacA was also shown to be dependent upon SecA we conclude that the initiation of translocation of this inner membrane polypeptide across the envelope occurs by the same mechanism as outer membrane and periplasmic proteins. The N-terminal 11 amino acids of mature OmpF, which in the hybrid are replaced by the N-terminal nine amino acids of DacA, carry no essential assembly signals since the hybrid protein is apparently assembled with equal efficiency to OmpF.

Amino Acid Sequence↗
PubMed1985

The effects of increased levels of niacin supplementation on growth rate and carcass composition of broiler chickens.

Four experiments were conducted to examine the response of broiler chickens to different levels of niacin. Practical-type diets, calculated to contain from 20.7 to 23.7 mg niacin per kg from intact ingredients, were fortified with a complete vitamin mixture which provided 33 mg supplemental niacin per kg of diet, in excess of the National Research Council (1977) suggested requirement of 27 mg per kg through 6 weeks of age. A niacinamide supplement was used to provide additional levels of 0, 33, or 66 mg per kg. Diets differed in content of added fat and energy levels in two of the experiments and in the presence or absence of animal protein sources in two others. The addition of niacinamide at 33 and 66 mg per kg to a diet already supplemented with 33 mg per kg from a complete vitamin premix, calculated to exceed the present NRC suggested requirement, resulted in improved body weight gains with sex differences noted in some experiments. Feed utilization was improved in some studies. There was no effect on the amount of abdominal fat or carcass dressing percentage. The results of these studies indicate that the modern rapidly growing broiler chick may require niacin levels greater than those generally recommended by the National Research Council (1977), which are based largely on studies where performance was considerably lower than obtained with the modern strains of broilers.

Animal Feed↗
PubMed1976

A feed additive to control flies in poultry manure.

To determine methoprene's effect on fly emergence from poultry manure, 18,000 8-wk.-old caged pullets were fed continuously 10 gm. of methoprene per ton of feed 42 days. Hatch mates (13,500) in an adjacent, similarly constructed and equipped house were fed untrated feed. Data on fly emergence were recorded twice a week after counting average numbers of flies in fly traps, in buckets of manure, and on fly strips and spot cards. Differences between average counts in the treated and control groups were significant by each of the four data-gathering methods. The methoprene reduced fly emergence by 77.0% in manure buckets, 65.5% in fly traps, but increased fly emergence 19.2% on fly strips, and 92.2% on spot cards. We attribute the increases in fly counts by the latter two counting methods in the treated house to migration of flies from adjacent untreated houses.

Animal Feed↗