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Biomedical subjects

G Ramsay

Publications and source records attributed to G Ramsay.

At least 91 records · Page 5Linked to original sources

Resuscitation in haemorrhagic shock--pulmonary and renal effects: an adverse effect of stabilised plasma protein solution on renal function?

In a model of severe canine haemorrhagic shock, greyhound dogs were randomly allocated to resuscitation with 0.9% saline, polygelin, hetastarch, or stabilised plasma protein solution (SPPS). Resuscitation was continued back to baseline pulmonary artery wedge pressure, and extravascular lung water (EVLW) and urine output were measured. EVLW following resuscitation was higher in the saline group than in any of the three colloid groups. Urine output following resuscitation was significantly lower in the SPPS group than in any other group. The results suggest that SPPS has an adverse effect on renal function in this model.

Animals↗

Direct measurement of the energetics of association between myelin basic protein and phosphatidylserine vesicles.

A newly designed high-sensitivity isothermal reaction calorimetry system has been used to investigate the thermodynamics of the association between myelin basic protein and phosphatidylserine vesicles. This instrument has allowed us to measure directly the energetics of the protein-lipid interaction under various conditions. Above the phospholipid phase transition temperature the enthalpy of association is highly exothermic amounting to -160 kcal/mol of protein. Below the phospholipid phase transition temperature the enthalpy of association is exothermic at protein/lipid ratios smaller than 1/50 and endothermic at higher protein/lipid ratios. These studies indicate that the association of myelin basic protein to phosphatidylserine vesicles consists of at least two stages involving different types of binding. The first stage, at low protein/lipid ratios, involves a strong exothermic association of the protein to the membrane and the second, at high protein/lipid ratios, a weaker association probably involving attachment of the protein to the membrane surface only. In the gel phase the second binding stage is endothermic and appears to be correlated with the formation of large vesicle aggregates. This vesicle aggregation is a reversible process dependent upon the physical state of the membrane. The isothermal titration studies have been complemented with high-sensitivity differential scanning calorimetry experiments. It is shown that the dependence of the phospholipid transition enthalpy on the protein/lipid molar ratio can be expressed in terms of the different protein-membrane association enthalpies in the gel and fluid phases of the membrane.

Animals↗

Human proto-oncogene N-myc encodes nuclear proteins that bind DNA.

N-myc is a gene whose amplification has been implicated in the genesis of several malignant human tumors. We have identified two proteins with molecular weights of 65,000 and 67,000 encoded by N-myc. The abundance of these proteins in tumor cells was consonant with the extent of amplification of N-myc. The two proteins apparently arose from the same mRNA, were phosphorylated, were exceptionally unstable, were located in the nucleus of cells, and bound to both single- and double-stranded DNA. These properties suggest that the products of N-myc and of the related proto-oncogene c-myc may have similar biochemical functions and that N-myc may be a regulatory gene. Our findings sustain the view that inordinate expression of N-myc may contribute to the genesis of several different human tumors.

Apudoma↗

Phenol cauterization for ingrown toenails.

A new clinic was set up to deal with all toenail problems referred to a large general hospital. Ingrowing toenails were the commonest problem dealt with and phenol cauterization, either partial or complete, was the standard form of treatment. Over a 2-year period 1013 phenol cauterizations were carried out on 631 patients. After a minimum of 12 months follow-up, the recurrence rate was 2.96%. All recurrences were successfully treated by repeat phenol cauterization. We conclude that phenol cauterization should replace surgical ablation in the treatment of ingrown toenails.

Adolescent↗

Validation of a prognostic score in critically ill patients undergoing transport.

Fifty consecutive critically ill patients transported between hospitals by a mobile intensive care team were assessed prospectively using a modification of the acute physiology and chronic health evaluation (APACHE II) sickness scoring system. Assessments were made before and after resuscitation, on return to base, and after 24 hours of intensive care. No patient died during transport. Twenty two patients died subsequently in hospital and 28 survived to return home. The mean score for the non-survivors before resuscitation was 21.7 and for the survivors 12.2 (p less than 0.0005). Among the non-survivors there was a significant fall in score with resuscitation but this did not alter their subsequent outcome. Neither group deteriorated during transport. The sickness score is a powerful method for determining prognosis, and employed longitudinally it may be useful in the assessment of treatment. It has important implications for the administration and organisation of regional intensive care services.

Adult↗

Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product.

Six monoclonal antibodies have been isolated from mice immunized with synthetic peptide immunogens whose sequences are derived from that of the human c-myc gene product. Five of these antibodies precipitate p62c-myc from human cells, and three of these five also recognize the mouse c-myc gene product. None of the antibodies sees the chicken p110gag-myc protein. All six antibodies recognize immunoblotted p62c-myc. These reagents also provide the basis for an immunoblotting assay by which to quantitate p62c-myc in cells.

Antibodies, Monoclonal↗

The protein encoded by the human proto-oncogene c-myc.

The proto-oncogene c-myc may play a role in controlling the growth and division of normal cells, and abnormalities of the gene have been implicated in the genesis of a substantial variety of human tumors. To facilitate further study of these issues, we developed antisera that permit the identification and isolation of the protein encoded by the human and other mammalian versions of c-myc. We found that c-myc(human) gives rise to at least two phosphoproteins with apparent molecular weights of 62,000 [pp62c-myc(human), the major product] and 66,000 [pp66c-myc(human), produced in smaller quantities and possibly a modified version of the Mr 62,000 protein]. Both proteins have relatively short half-lives of approximately equal to 30 min. Mouse c-myc encodes similar proteins with molecular weights of 64,000 and 66,000. The use of cells transformed by DNA-mediated gene transfer sustained previous deductions that the entire coding domain of c-myc(human) is contained in the second and third exons of the gene and resolved previous ambiguities by showing that analogous exons specify the entire protein product of c-myc(chicken). Tumor cells containing amplification of c-myc(human) produce relatively large amounts of pp62/pp66c-myc(human). By contrast, translocations of c-myc found in cells derived from Burkitt lymphoma appear merely to sustain expression of c-myc(human) at levels found also in nontumorigenic lymphoblastoid cells, rather than to increase expression of the gene to manifestly abnormal levels.

Animals↗

The product of the retroviral transforming gene v-myb is a truncated version of the protein encoded by the cellular oncogene c-myb.

Avian myeloblastosis virus (AMV) is an oncogenic retrovirus that rapidly causes myeloblastic leukemia in chickens and transforms myeloid cells in culture. AMV carries an oncogene, v-myb, that is derived from a cellular gene, c-myb, found in the genomes of vertebrate species. We constructed a plasmid vector that allows expression of a portion of the coding region for v-myb in a procaryotic host. We then used the myb-encoded protein produced in bacteria to immunize rabbits. The antisera obtained permitted identification of the proteins encoded by both v-myb and chicken c-myb. The molecular weights of the products of v-myb and c-myb (45,000 and 75,000 respectively) indicate that the v-myb protein is an appreciably truncated version of the c-myb protein.

Animals↗

Phosphorylation of specific sites in the gag-myc polyproteins encoded by MC29-type viruses correlates with their transforming ability.

The putative transforming proteins of the four acute leukaemia viruses belonging to the MC29 subgroup were shown to be phosphorylated in vivo. Comparison of the MC29 and CM11 encoded phosphoproteins revealed identical tryptic phosphopeptide maps, with both the gag and myc domains being phosphorylated. In contrast, the MH2 phosphoprotein was only phosphorylated on the gag domain. Analysis of partial transformation-defective MC29 deletion mutants revealed that the deletions had removed the v-myc specific phosphopeptides. Phosphoamino acid analysis showed that these deleted phosphopeptides were phosphorylated on threonine. Moreover, a back mutant that had regained transforming ability had regained these phosphopeptides. These studies correlate the phosphorylation of the gag-myc protein with the transformation capability of the virus.

Amino Acids↗

Two virus-specific rna species are present in cells transformed by defective leukemia virus OK10.

OK10 is a defective leukemia virus which shares some biological and biochemical properties of avian myelocytomatosis virus (MC29). We investigated the pattern of transcription of OK10 in both quail and chicken cells. In both cell types, OK10 produced two polyadenylated RNA species of 8.6 and 3.5 kilobases, which both contained sequences derived from the 5' end of the genome and also the presumed transforming gene (myc). This is a novel form of expression for defective leukemia viruses of the MC29 subgroup and may indicate that there is an as-yet-unidentified protein produced in OK10-infected cells which may be involved in transformation.

Animals↗

Cell transformation by avian defective leukaemia viruses.

A comparative study of seven independently isolated defective leukaemia viruses has been carried out. Phenotypic analysis of the chicken bone marrow cells transformed in vitro allowed the separation of these seven viruses into three groups based on the differentiation phenotype of the transformed cell. Nucleic acid hybridization studies revealed that these seven viruses had acquired cellular sequences. Interestingly, these studies also showed that the viruses within the same biological grouping had acquired related sequences. This indicates that viruses that have acquired the same or similar cellular sequences have very similar oncogenic capabilities. Analysis of proteins expressed in cells transformed by these viruses demonstrated that the cellular sequences were usually inserted within the gene for the viral core proteins, gag. Therefore the cellular sequences are expressed as a gag-related fusion protein which has an amino-terminal region derived from the gag gene and a carboxy-terminal half derived from the cellular sequences. Two exceptions to this are discussed. The general conclusion from these studies is that defective leukaemia viruses transform cells by virtue of acquired host cellular sequences. The ability of these viruses to transform cells and the target cell specificity of the transformation depends on these cellular sequences.

Alpharetrovirus↗

Mutants of avian myelocytomatosis virus with smaller gag gene-related proteins have an altered transforming ability.

Avian myelocytomatosis virus strain MC29 is a replication-defective avian oncovirus which in newborn chickens causes myelocytomatosis and liver and kidney tumours. In vitro infection of bone marrow cells gives rise to colonies of transformed macrophage-like cells, and cloned viruses is also capable of transforming fibroblasts. The genome of MC29 contains cellular sequences which are closely related to those in other defective leukaemia viruses with similar transforming spectra. Consequently, these cellular sequences have been postulated to represent a new oncogene which has been designated mac, for macrophage transformation. MC29-transformed cells contain a gag gene-related protein of a 110,000 molecular weight (MW) (p110), which by tryptic peptide analysis has been shown to be a fusion product comprised of a gag gene-derived sequences and sequences which are presumed to be coded by the adjacent mac gene. These findings suggest that this protein may be implicated in transformation by MC29. We now describe three mutants of MC29 and synthesize smaller gag gene-related proteins. These mutants have an altered ability to transform bone marrow cells but not fibroblasts. This demonstrates for the first time a direct involvement of the p110 protein of MC29 in transformation.

Animals↗

OK10, an avian acute leukemia virus of the MC 29 subgroup with a unique genetic structure.

The RNA of defective avian acute leukemia virus OK10 was isolated from a defective virus particle, released by OK10-transformed nonproducer avian fibroblasts, as a 60S complex consisting of 8.6-kilobase subunits. Oligonucleotide fingerprinting and RNA.cDNA hybridization identified two sets of sequences in OK10 RNA: group-specific sequences, which are related to all nondefective members of the avian tumor virus group, and a sequence closely related to the subgroup-specific sequences (mcv) of the myelocytomatosis virus (MC29) subgroup of avian acute leukemia viruses. Hence, OK10 is classified as a member of the MC29 subgroup of avian tumor viruses, in agreement with classification based on its oncogenic spectrum. The group-specific sequences of OK10 RNA include partial (Delta) pol and env genes, a c-region, and, unlike those of all other members of the MC29 subgroup, a complete gag gene. Oligonucleotide mapping revealed 5'-gag-Deltapol-mcv-Deltaenv-c-3' as the order of the subgroup-specific and group-specific elements of OK10 RNA. The genetic unit gag-Deltapol-mcv, measuring approximately 6.4 kilobases, codes for the nonstructural, presumably transforming, 200,000-dalton OK10-specific protein and also includes the gag gene coding for the internal virion proteins. Because gag is the only intact virion gene shared in addition to regulatory RNA sequences between OK10 and nondefective avian tumor viruses, it is concluded that the gag gene is sufficient for the formation of a defective virus particle. Comparisons among the RNAs and gene products of different viruses of the MC29 subgroup show that they share 5'-terminal gag-related and internal mcv sequences but differ from each other in intervening gag-, pol-, and mcv-related sequences. It follows that the probable transforming genes and their protein products have two essential domains, one consisting of conserved 5' gag-related and the other of 3' mcv-related sequence elements. In the light of this and previous knowledge we can now distinguish two designs among five different transforming onc genes of avian tumor viruses: onc genes with coding sequences unrelated to virion genes, like those of Rous sarcoma virus and avian myeloblastosis virus, and onc genes with coding sequences that are hybrids of virion genes and specific sequences, like those of the MC29 subgroup viruses, of avian erythroblastosis virus, and of Fujinami sarcoma virus.

Animals↗

Experimental studies of the etiology of genital exhibitionism.

Several studies are reported which examine the critical stimuli and responses as well as personality factors important in genital exhibitionism. Using penile volume measurement, sex history questionnaires, personality tests, and behavioral observations, it was found that (1) exhibitionists responded most to mature females and were comparable to normals in reactions to children and men; (2) while exhibitionists indicated narcissistic desires in exposing, in a laboratory study they did not differ from controls in reactions to exposing with various reactions of the female, from sexual arousal and admiration to fear and anger; (3) the only strong features distinguishing exhibitionists from controls and other sexually anomalous subjects were peeping associated with orgasm and outdoor solitary masturbation; (4) exhibitionists seemed to be less assertive and less feminine than controls, but results were weak and inconsistent; (5) exhibitionists and controls did not differ in separation and divorce or marital satisfaction; (6) blood testosterone and penile reactivity of exhibitionists were within normal limits. Overall, the results suggest that most major theories of genital exhibitionism are wanting. It is suggested that narcissism and pedophilia be examined further in connection with exhibitionism.

Adult↗