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Biomedical subjects

J M Devine

Publications and source records attributed to J M Devine.

At least 19 recordsLinked to original sources

Industry's perception and use of occupational exposure limits.

Market research was carried out to determine industry's perception of occupational exposure limits (OELs) and the extent to which they influence the selection of measures to control exposure. Telephone interviews were carried out with 1000 randomly selected users of chemicals, 400 from establishments with some use of chemicals and 600 from establishments with chemicals in daily use. 150 interviews were also carried out with Trade Union Health and Safety Representatives. The interviews covered basic information on chemicals used, sources of information, risk reduction measures used and understanding of COSHH and OELs. Most respondents came from firms with 10 employees or less (75%, all user group; 57%, heavy user group), closely reflecting the profile of British industry. In contrast, most (77%) Trade Union Health and Safety Representatives came from firms with at least 100 employees. Respondents in the all user group were drawn from across the whole range of industrial activity, whereas the heavy users were concentrated in manufacturing. The results showed that in making decisions on what control measures to use most users rely heavily on information from suppliers and personal experience and rather less on information from sources such as Trade Associations and HSE. Most respondents reported that steps were taken to protect employees. The use of personal protective equipment featured highly, followed by process controls. Little consideration was given to the possibility of substitution. Awareness of COSHH was limited with 65% of the all user group and 53% of the heavy user group being unaware of any legal requirements for establishments which manufacture or work with chemicals. Awareness of OELs was similarly limited with 19% of the all user group and 32% of the heavy user group having any real understanding. The results from Trade Union Representatives showed that overall they are somewhat better informed than chemical users in the small firms surveyed.

Air Pollutants, Occupational↗

Plasminogen mutants activated by thrombin. Potential thrombus-selective thrombolytic agents.

Plasmin, the enzyme responsible for degradation of fibrin in blood clots and thus thrombolysis, is normally formed when its zymogen plasminogen is activated by cleavage of the Arg561-Val562 bond by specific plasminogen activators. We have altered the activation characteristics of plasminogen by substituting the P3, P2, and P1' cleavage site residues with sequences from thrombin-cleavable proteins to produce a novel thrombolytic agent which instead is activated by the blood clotting system. Plasminogen variants with thrombin cleavage sites from fibrinogen, the thrombin receptor, factor XIII, and factor XI were cleaved by thrombin with times to 50% cleavage of 28 h, 2.5 h, 5.7 min, and 3 min, respectively. In vitro clot lysis studies have shown that a variant in which the P3-P1' residues of plasminogen were substituted by the P7-P1' residues (Thr363-Ile370) from factor XI (T51) was sufficiently rapidly cleaved by thrombin to be activated by the endogenous thrombin produced by the coagulation cascade, resulting in rapid clot dissolution. Thrombin-activatable plasminogen therefore has the capacity to short circuit the physiological hemostatic mechanisms and produce fibrinolytic activity localized to the site of thrombin formation, that is, at the thrombus itself. The novel activation mechanism combined with the natural long circulating half-life of plasminogen gives this type of thrombolytic agent the potential for thrombus-selective plasmin generation and an extended duration of action.

Amino Acid Sequence↗

Group treatment of secondary erectile dysfunction.

The effects of three group treatment formats on 20 men with secondary erectile dysfunction and their partners were contrasted. After a comprehensive medical and psychological screening, each couple was assigned to one of three treatment groups (Communication Technique Training, Sexual Technique Training, Combination Treatment) or to one of two control groups (Attention-Placebo, No-Treatment). Couples in the three treatment groups and the attention-placebo group participated in their respective formats in twice-weekly sessions for a total of 20 hours. The no-treatment control group received sex education and treatment after a 5-week waiting list period. All three treatment groups fostered substantial gains so that between-format differences were not statistically significant. Subject variables which predicted success/experience ratio gains included age of the male partner, perceived level of relationship adjustment, and the male partner's success/experience ratio prior to treatment. Eighty-one percent of the treated men reached the criterion of 80% or greater success/experience ratio (successful penetration and subsequent ejaculation) at the 6-month follow-up. Good nocturnal tumescence prior to treatment was correlated with a better treatment outcome than poor tumescence.

Adult↗

The isolation and characterization of the Blym-1 transforming gene.

There are a number of similarities between chicken bursal lymphomas and human Burkitt's lymphomas. Both lymphomas are associated with viral infection, by LLV in bursal lymphomas and Epstein-Barr virus in Burkitt's lymphoma. Avian lymphoid leukosis virus integration is associated with enhanced c-myc expression, while the role EBV plays in tumorigenesis remains unclear. In Burkitt's lymphoma, however, c-myc activation does occur as a result of specific chromosomal translocations involving the human c-myc locus. Furthermore, the activated transforming genes detected by transfection of both bursal lymphoma and Burkitt's lymphoma DNAs are homologous members of the Blym family of genes. These similarities between chicken and human lymphomas provide evidence that viral involvement and oncogene activation are significant in tumor development and suggest they are involved in the multi-step progression to the neoplastic phenotype. The function of the Blym genes remains to be determined. Although the chicken and human Blym genes are only distantly related, they have maintained their homology to the amino-terminal regions of transferrins. This fact may reflect some functional constraint on the evolution of these genes. It is therefore possible that transforming genes such as Blym may function via a transferrin-related mechanism.

Animals↗

Nucleotide sequence of a human Blym transforming gene activated in a Burkitt's lymphoma.

The nucleotide sequence of a human Blym-1 transforming gene activated in a Burkitt's lymphoma cell line was determined. This sequence predicts a small protein of 58 amino acids that is 33 percent identical to the predicted product of chicken Blym-1, the activated transforming gene of chicken B cell lymphomas. Both the human and chicken Blym-1 genes exhibit significant identity to an amino-terminal region of transferrins.

Amino Acid Sequence↗

Characterization of sequence elements at the 5' end of a discoidin I gene isolated from Dictyostelium discoideum.

The discoidin I genes of Dictyostelium discoideum encode a family of three closely related developmentally regulated lectins which may play a role in cell cohesion. We have isolated a genomic clone containing the 5' half of a discoidin I gene with 12kb of flanking sequence and we have identified the discoidin I polypeptide encoded by this gene. We have determined part of the nucleotide sequence of the cloned segment and have hence determined the N-terminal amino acid sequence of the encoded polypeptide. The nucleotide sequence upstream of the AUG initiation codon was unusually AT rich, with 94% AT base pairs in the 171 nucleotides for which sequence was determined. However, having determined the start point of transcription ('cap' site) two striking features of similarity with other eukaryotic structural genes became apparent. The sequence TATAAA was present 33 nucleotides upstream from the 'cap' site and the sequence CCAAT was present a further 20 nucleotides upstream.

Amino Acid Sequence↗

Differential expression of the members of the discoidin I multigene family during growth and development of Dictyostelium discoideum.

Discoidin I and II are lectins synthesized during the aggregation of Dictyostelium discoideum amoebae which may play a role in cellular cohesion. Discoidin I was thought to consist of two major polypeptides, but we show that there are three. The N-terminal amino acid sequence of the polypeptides has been predicted by determining part of the nucleotide sequence of their respective mRNAs. We obtained the nucleotide sequences by reverse transcription of the mRNAs, using as primers, fragments derived from the coding region of two cloned discoidin I sequences, and utilizing cross hybridization to the various mRNA species and differences in the length of their 5' noncoding regions to isolate fragments for DNA sequencing. We used primer extension to measure the relative concentration of the three major discoidin I mRNA sequences. We show that during development changes in the abundance of all three mRNA sequences occur coordinately. In cells growing in nutrient broth, however, only two of the three major discoidin I mRNA sequences accumulate, and if such cells are grown to a very high density, both sequences disappear. These results indicate that the coordination of discoidin I gene expression is not obligatory and that the members of this multigene family may differ in the mode of their induction during normal development.

Base Sequence↗

Characterization and transcription analysis of a cloned sequence derived from a major developmentally regulated mRNA of D. discoideum.

The plasmid pDd 812 contains a portion of a poly(A)+ RNA sequence isolated from developing cells of the cellular slime mold Dictyostelium discoideum (Williams and Lloyd, 1979). The poly(A)+ RNA complementary to this plasmid shows an increase in concentration during the first 4 hr of development followed by a decrease in concentration during the following 4 hr. This RNA is very abundant after 3-4 hr of development, constituting at least 2% of the poly(A)+ RNA population. In this study, we demonstrate that this poly(A)+ RNA is an mRNA sequence by translating the RNA complementary to pDd 812 in a heterologous system. The mRNA directs the synthesis of a major polypeptide of 33,000 daltons and a minor polypeptide of 31,000 daltons. We have used the plasmid DNA immobilized on filters to analyze the transcription of this RNA sequence in isolated nuclei. The amount of transcript synthesized in nuclei isolated at various stages of development which was complementary to pDd 812 changed in the same way as did the cytoplasmic concentration of this RNA--that is, maximal transcription occurred after 3-4 hr of development. Because this result was observed using labeling periods as short as 5 min, we believe that this change is unlikely to reflect a change in the rate of processing of RNA. We interpret these results to indicate that, at least in part, the control of the synthesis of this RNA is at the level of gene transcription.

Base Sequence↗