Search PubMed⌕ Search

Biomedical subjects

E W Jones

Publications and source records attributed to E W Jones.

At least 91 records · Page 5Linked to original sources
PubMed1986

The detection of endothelial cell antigens in cutaneous tissue using methacarn and periodate lysine paraformaldehyde fixation.

The use of monoclonal antibodies with endothelial cell specificity has prompted a search for methods of fixation which combine the morphology of paraffin-embedded tissue, with preservation of labile membrane antigens. Immunohistochemical staining using a variety of endothelial cell markers was compared in tissue fixed in formalin, methacarn, periodate lysine paraformaldehyde (PLP) and in frozen tissue. Whilst lectin-binding with Ulex europaeus agglutinin I (UEA) and localisation of Factor VIII-related antigen (FVIII RA) and laminin was well-visualised in methacarn-fixed and PLP-fixed tissue, fixation in PLP was necessary for the two monoclonal antibodies, PAL-E and EN4. PLP fixation has considerable potential for investigating the histogenesis of vascular tumours, particularly in Kaposi's sarcoma where frozen tissue represents a biological hazard. The normal staining pattern of human dermal vasculature is described in relation to the above endothelial cell antigens.

Acetates↗
PubMed1986

Giant solitary trichoepitheliomas located in the perianal area: a report of three cases.

Very large solitary trichoepitheliomas which arose in the perianal region in three patients are described. Although these tumours showed a striking histological similarity to classical multiple or solitary trichoepitheliomas of the face, they differed in their massive size, unusual location and by their involvement of deeper tissue. We suggest that giant solitary trichoepitheliomas is a distinct variant of trichoepithelioma that may have a predilection for the perianal region. At this site this rare tumour must be distinguished from basal cell carcinoma of the perineum and from malignant basaloid (cloacogenic) carcinoma of the anal canal.

Aged↗
PubMed1986

The PEP4 gene encodes an aspartyl protease implicated in the posttranslational regulation of Saccharomyces cerevisiae vacuolar hydrolases.

pep4 mutants of Saccharomyces cerevisiae accumulate inactive precursors of vacuolar hydrolases. The PEP4 gene was isolated from a genomic DNA library by complementation of the pep4-3 mutation. Deletion analysis localized the complementing activity to a 1.5-kilobase pair EcoRI-XhoI restriction enzyme fragment. This fragment was used to identify an 1,800-nucleotide mRNA capable of directing the synthesis of a 44,000-dalton polypeptide. Southern blot analysis of yeast genomic DNA showed that the PEP4 gene is unique; however, several related sequences exist in yeasts. Tetrad analysis and mitotic recombination experiments localized the PEP4 gene proximal to GAL4 on chromosome XVI. Analysis of the DNA sequence indicated that PEP4 encodes a polypeptide with extensive homology to the aspartyl protease family. A comparison of the PEP4 predicted amino acid sequence with the yeast protease A protein sequence revealed that the two genes are, in fact, identical (see also Ammerer et al., Mol. Cell. Biol. 6:2490-2499, 1986). Based on our observations, we propose a model whereby inactive precursor molecules produced from the PEP4 gene self-activate within the yeast vacuole and subsequently activate other vacuolar hydrolases.

Amino Acid Sequence↗
PubMed1986

Histogenesis of Kaposi's sarcoma in patients with and without acquired immune deficiency syndrome (AIDS).

Immunohistochemical studies were performed in thirty skin biopsies from patients with Kaposi's sarcoma, who did and did not have the acquired immune deficiency syndrome (AIDS). Tumour histogenesis was rigorously tested using a battery of endothelial cell markers, which included two new monoclonal antibodies, EN4 and PAL E. These are both specific for endothelial cells and can be visualised in appropriately fixed paraffin embedded tissue. Whereas EN4 labels all endothelial cells, PAL E is negative in endothelium of lymphatic derivation. Lectin binding with Ulex europaeus agglutinin 1 (UEA-1) and the presence of factor VIII related antigen (FVIIIRA) and laminin were also examined. In nodular lesions of Kaposi's sarcoma the spindle cell areas were positive with EN4 and UEA-1, negative with PAL E, and showed focal staining for FVIIIRA and laminin. These results confirm that the tumour is of endothelial cell origin. Six patch stage lesions showed a network of angulated spaces, lined by cells that were positive with EN4 and UEA-1, negative with PAL E and anti-FVIIIRA, and showed only weak staining for laminin. This pattern was observed in both AIDS and non-AIDS related cases and strongly favours a lymphatic derivation for the tumour. This has important implications as it suggests that lymphatic endothelium may have special characteristics that lead to neoplastic transformation in patients with retrovirus infection.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Blood magnesium values in healthy cattle and in cattle affected with anaplasmosis and eperythrozoonosis.

Magnesium (Mg) concentrations in plasma, serum, and erythrocytes (RBC) of calves subjected to splenectomy (SP), splenectomy-induced eperythrozoonosis (EP), and experimentally induced anaplasmosis (AN) were determined and compared with pre-SP, pre-EP, and pre-AN values. Mean serum and plasma Mg concentrations varied in parallel through most periods of the trial. Both were highest after SP, but neither value was significantly different from the pre-SP concentrations. Mean serum and plasma Mg values varied inversely with mean RBC values after SP and EP. Mean RBC Mg values increased significantly from previous periods during EP and AN and after AN, with the values after AN being significantly higher than those at all other periods. Mean plasma, serum, and RBC Mg concentrations were correlated to both mean percentage of parasitemia (%P) and packed-cell volume (PCV). The RBC Mg values increased significantly after mean %P reached 20 and the PCV began to decrease. There was evidence for a distinct lag variation in increasing RBC Mg concentrations with respect to both mean %P and PCV during AN. A strong correlation was observed between the RBC Mg values and the %P occurring 5 days previously and the PCV occurring 3 days previously.

Anaplasmataceae Infections↗
PubMed1985

The effects of dazoxiben, an inhibitor of thromboxane synthetase, on cold-induced forearm vasoconstriction and platelet behaviour in different individuals.

The effect of dazoxiben, a thromboxane synthetase inhibitor, on cold-induced forearm vasoconstriction was determined in two groups of human volunteers, those in whom dazoxiben abolished the platelet aggregation and release reaction induced by sodium arachidonate (group I) and those in whom it did not (group II). Dazoxiben abolished cold-induced forearm vasoconstriction in group I volunteers but not in those of group II. These results imply a correlation between platelet behaviour and cold-induced changes in vascular tone. In the group I volunteers the effect of dazoxiben on cold-induced vasoconstriction was abolished by 1800 mg of aspirin, but not by 40 mg. Since the lower dose of aspirin inhibits platelet cyclo-oxygenase but has no effect on cyclo-oxygenase in blood vessel walls, it is possible that platelets play no part in the modulation of vascular tone by dazoxiben. It is more likely that the effects of dazoxiben are confined to the vessel wall.

Adult↗
PubMed1985

Lichen aureus: a localized persistent form of pigmented purpuric dermatitis.

Localized persistent pigmented macules and plaques due to a chronic form of pigmented purpuric dermatitis are described in forty-two patients. The designation 'lichen aureus' for this eruption can be justified because of the striking yellowish or bronze-like colour assumed by many of the lesions. The lower legs were the commonest sites but other body regions can be affected also. Histologically lichen aureus differs from other pigmented purpuric dermatoses in the density of the lichenoid tissue reaction and the marked accumulation of pigment-containing macrophages. Recently developed endothelial cell markers have been studied in selected cases.

Adolescent↗
PubMed1985

A microbiological study of diabetic foot lesions.

The bacterial nature of infected foot lesions presenting to a diabetic unit during the course of twelve months was studied. Fifty-six swabs were obtained from 25 patients. Swabs were processed within ten minutes of being collected. An average of 3.3 organisms per swab were isolated, Staphylococcus aureus was the most common bacterial species isolated, while anaerobic bacteria comprised 10% of the isolates. Sensitivity testing of the isolates against commonly used antibiotics showed that the antimicrobial regimen that we have previously used empirically on such patients may not always be optimal.

Adult↗
PubMed1985

The management of splenic abscess.

We report three patients with splenic abscess whom we attempted to treat without recourse to open surgery. Medical treatment alone was successful in one case, and medical treatment combined with percutaneous drainage was successful in the second. Splenectomy was required in the third case after failure of medical treatment and complications of percutaneous drainage. The difficulties in diagnosing splenic abscess are reviewed and the indications for splenectomy or percutaneous drainage, as opposed to medical treatment are considered.

Abscess↗
PubMed1984

The synthesis and function of proteases in Saccharomyces: genetic approaches.

Genetic analysis has clarified the role of the major defined proteases in the life of yeast cells. The proteases of the vacuole are clearly involved in the massive proteolysis that occurs when cells are starved for nitrogen and in the (re)utilization of peptides. They appear not to be involved in any of the specific proteolyses that have been described. kex1, kex2, ste13, bar1 (sst1), and pep4 mutants have the characteristics expected of mutants defective in specific proteolytic events. Hence, the genetic attack on these specific proteolyses and the identification and characterization of the responsible proteases seem well under way and we can expect answers in the near future. The biggest lacuna in our understanding of proteolysis in yeast is the identity of the protease(s) or proteolytic system(s) involved in metabolically triggered proteolytic degradations and in housekeeping functions such as degradation of nonfunctional subunits and aberrant proteins. Genetic entries into these problems appear to be rare or difficult. Here lies the greatest challenge.

Cell Cycle↗
PubMed1983

Synthesis and maturation of the yeast vacuolar enzymes carboxypeptidase Y and aminopeptidase I.

We have studied the two vacuolar enzymes carboxypeptidase Y and aminopeptidase I from Saccharomyces cerevisiae with respect to biosynthesis, maturation and transfer from their site of synthesis into the organelle. The levels of translatable mRNA for these two proteins increase more than 10-fold at the end of the exponential growth period on glucose as carbon source and decrease again in the stationary phase. Two precursors of carboxypeptidase Y have been identified by in vivo pulse-labelling with [35S]methionine. These differ in their amount of carbohydrate as shown by inhibition of N-linked glycosylation with tunicamycin. The first is a protein with an apparent molecular weight of 67 kDa, which can be converted into the mature 60-kDa protein via an intermediate of 69 kDa. In the pep4-3 mutant, which is disturbed in the maturation of several vacuolar enzymes (Hemmings, B.A., Zubenko, G.S., Hasilik, A. and Jones, E.W. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 435-439), the 69-kDa precursor accumulates in the vacuole. This suggests that the final proteolytic cleavage of carboxypeptidase Y can occur in the vacuole.

Aminopeptidases↗
PubMed1983

Venous thrombosis in diabetes mellitus.

The incidence over 7 days of isotopically-detected calf and popliteal vein thrombosis was determined in a group of 60 diabetic patients admitted to hospital with myocardial infarction, heart failure or stroke, or for abdominal surgery. The result was compared with the incidence in 60 control subjects matched for age, sex and presenting diagnosis. Twenty-one diabetic patients developed positive 125I-fibrinogen scans, compared with 19 control subjects; this difference is not significant. We conclude that diabetes is not associated with an enhanced risk of thrombosis in veins. It is therefore possible that the arterial and capillary abnormalities found in diabetes may arise from mechanisms other than a generalised thrombotic tendency.

Aged↗
PubMed1983

A thromboxane synthetase inhibitor in Raynaud's phenomenon.

The balance between thromboxane A2 (a vasoconstrictor) and prostacyclin (a vasodilator) may be important in the pathogenesis of Raynaud's phenomenon. Dazoxiben is a selective inhibitor of thromboxane synthetase, with no effect on prostacyclin synthetase. It has been shown to abolish cold induced forearm vasoconstriction in normal volunteers. We have compared its effect with that of placebo in a double blind crossover study in eight patients with severe Raynaud's phenomenon. No consistently clinically useful benefit was demonstrated from three weeks' treatment with dazoxiben, and there were no significant changes in finger temperature or finger blood flow. We conclude that dazoxiben at this dosage is unlikely to be of practical clinical benefit in Raynaud's phenomenon.

Adult↗
PubMed1983

Mutations in PEP4 locus of Saccharomyces cerevisiae block final step in maturation of two vacuolar hydrolases.

The biosynthesis of carboxypeptidase Y (EC 3.4.16.1) and proteinase A (EC 3.4.23.6) in yeast cells involves a series of posttranslational events, the last of which is dependent upon a function supplied by the PEP4 gene. Because pep4 mutations result in a 90-95% reduction in the levels of activity of at least three additional vacuolar hydrolases, it is likely that these, and perhaps all, yeast vacuolar hydrolases are synthesized as inactive precursors, which mature by a common mechanism that depends upon a function supplied by the PEP4 gene. The pep4 mutation shows an apparent gene dosage effect on levels of activity of proteinases A and B but not on the level of activity of carboxypeptidase Y. This effect appears to come about because the maturation machinery is capable of discriminating among these hydrolase precursors.

Aspartic Acid Endopeptidases↗
PubMed1983

Effects of dazoxiben and low-dose aspirin on platelet behaviour in man.

1 We have studied the effects on platelet behaviour of ingestion of the thromboxane synthetase inhibitor dazoxiben (UK 37248), by healthy subjects, and compared the results with the effects of a low dose of aspirin (a cyclo-oxygenase inhibitor), and of a combination of dazoxiben and a low dose of aspirin. 2 Dazoxiben ingestion prevented the release reaction induced by sodium arachidonate (NaAA) in platelet-rich plasma (PRP) from some individuals ("responders") but not in PRP from others ("non-responders"). In vitro testing of PRP from the same subjects, incubated with 10(-4)M dazoxiben, correlated with the effect of dazoxiben ingestion on NaAA-induced release. Platelets from "non-responders" tended to undergo a more extensive release reaction than platelets from "responders" even in the absence of any drug although there was some overlap between the results in the two groups. Platelets from "non-responders" required significantly lower concentrations of NaAA to induce release reaction than platelets from "responders". Platelets from "responders" and "non-responders" did not differ in the amount of malondialdehyde (MDA) produced or in the effectiveness with which dazoxiben ingestion inhibited MDA production. 3 Low dose aspirin had comparable effects on NaAA-induced release to dazoxiben, but in contrast to dazoxiben, the effectiveness of low-dose aspirin in inhibiting NaAA induced release reaction was related to its effectiveness in inhibiting MDA generation. 4 Neither dazoxiben nor low-dose aspirin significantly affected the release reaction induced by adenosine diphosphate (ADP), although both drugs significantly inhibited adrenaline-induced release. 5 A combination of dazoxiben and low dose aspirin had a greater effect on platelet behaviour in response to NaAA, ADP, and adrenaline than either drug alone.

Adenosine Diphosphate↗
PubMed1983

Effects of dazoxiben, an inhibitor of thromboxane synthetase, on forearm vasoconstriction in response to cold stimulation, and on human blood vessel prostacyclin production.

1 In healthy male volunteers dazoxiben (UK 37248), an inhibitor of thromboxane synthetase, abolished the arterial and venous vasoconstriction produced in the forearm by cold stimulation. 2 Aspirin alone had no effect on this vasoconstriction but negated the effect of dazoxiben. 3 In vitro dazoxiben increased the production of prostacyclin by human arteries and veins. 4 By reducing the synthesis of thromboxane A2, a potent vasoconstrictor, and by increasing the synthesis of prostacyclin, a potent vasodilator, dazoxiben may have a therapeutic role in conditions associated with abnormal vasoconstriction.

Adult↗
PubMed1982

PEP4 gene function is required for expression of several vacuolar hydrolases in Saccharomyces cerevisiae.

The pep4-3 mutation results in a 90-95% reduction in the levels of five vacuolar hydrolases in yeast, including proteinases A and B, carboxypeptidase Y, RNase(s) and the repressible alkaline phosphatase. The mutation is without effect on two secreted glycoproteins, on an enzyme of the vacuolar membrane, and on a proteinase located outside of the vacuole. Mutations at the PEP4 locus exhibit a dosage effect on the levels of some, but not all, of the enzymes whose expression requires the function of the gene.

Alkaline Phosphatase↗