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Biomedical subjects

J Oliver

Publications and source records attributed to J Oliver.

At least 91 records · Page 5Linked to original sources
PubMed1995

Aberrant p53 expression predicts clinical resistance to cisplatin-based chemotherapy in locally advanced non-small cell lung cancer.

The development of cisplatin-based induction chemotherapy followed by surgical resection or radiation has improved the poor prognosis of stage III non-small cell lung cancer (NSCLC). In vitro studies indicate that p53 can modulate cisplatin-induced cytotoxicity, but the molecular genetic features determining response or resistance to cisplatin in vivo must be defined. For this reason, tumor specimens from 52 patients with stage IIIA NSCLC entered in a prospective clinical trial of cisplatin-based induction chemotherapy followed by surgical resection were examined for p53 expression by immunohistochemical staining before and after induction chemotherapy. p53 expression was correlated with clinical and pathological response using Fisher's exact test. No correlation was established between p53 expression and clinical response because 47 of the 52 patients studied had a major response. However, a significant association was observed between aberrant p53 expression and resistance to chemotherapy as assessed by pathological response. Only 3 of the 20 patients whose tumors exhibited a high level (+ + to + + + +) of p53 staining experienced a major (+ + + to + + + +) pathological response to chemotherapy. Only 7 of 52 cases examined before and after chemotherapy treatment exhibited a change in the level of p53 expression after cisplatin-based chemotherapy. These results indicate that cisplatin alters p53 expression infrequently and suggest a direct link between aberrant p53 expression and resistance to cisplatin-based chemotherapy in NSCLC.

Carcinoma, Non-Small-Cell Lung↗
PubMed1995

In vivo release of interleukin-1 beta into hypothalamic extracellular fluid in rats: effects of repeated sampling.

Interleukin-1 beta (Il-1 beta) concentrations in extracellular fluid (ECF) withdrawn at 10-min intervals through a push-pull cannula (PPC) located in the hypothalamus were studied in freely behaving male rats for 1 h at 24 and 72 h and again at 7 days after PPC implantation. Il-1 beta concentrations in ECF were similar in the latter. However, when ECF was sampled at 3 h and again 7 days after PPC implantation, Il-1 beta concentrations were greatly elevated at 7 days when compared to all other intervals. These results demonstrate how the relationships between Il-1 beta measured in ECF and the conditions of measurement appear to be integral parts of a whole intracerebral system: cytokine concentrations appear to be inextricably bound to intrahypothalamic conditions created by the sampling device presence and frequency of use.

Animals↗
PubMed1995

The translocation, folding, assembly and redox-dependent degradation of secretory and membrane proteins in semi-permeabilized mammalian cells.

We describe here a semi-permeabilized cell-system which reconstitutes the efficient synthesis, translocation, folding, assembly and degradation of membrane and secretory proteins. Cells grown in culture were treated with the detergent digitonin which selectively permeabilized the plasma membrane leaving the cellular organelles, such as the endoplasmic reticulum (ER) and trans-Golgi network intact. These permeabilized cells were added to an in vitro translation system, either wheatgerm or reticulocyte lysate, supplemented with RNA coding for either membrane or secretory proteins. Efficient translocation and modification of proteins by these cells was demonstrated by protease protection, photocross-linking of nascent chains to components of the translocation apparatus and by post-translational modifications such as glycosylation or hydroxylation. A comparison was made between the ability of semi-permeabilized cells and microsomal vesicles to fold and assemble proteins. The results show that the intact ER within these cells can assemble proteins much more efficiently than vesicularized ER. Furthermore, the semi-permeabilized cells carried out the redox-dependent degradation of tissue-type plasminogen activator. This system has all the advantages of conventional cell-free systems, including speed and, importantly, the ability to manipulate the components of the assay, while retaining intracellular organelles and, therefore, allowing cellular processes to occur as they would in the intact cell.

Animals↗
PubMed1995

The Sec61 complex is essential for the insertion of proteins into the membrane of the endoplasmic reticulum.

Cross-linking studies have implicated Sec61 alpha as the principal component adjacent to newly synthesised membrane proteins during insertion into the endoplasmic reticulum. Using proteoliposomes which have been reconstituted from purified components of the endoplasmic reticulum [Görlich, D and Rapoport, T.A., Cell 75 (1993) 615-630] we have found that the Sec61 complex, consisting of three subunits, is essential for the insertion of single-spanning membrane proteins. This is true for signal-anchor proteins of both orientations, and for proteins with a cleavable signal sequence. These results support the view that Sec61 alpha is a major component of the ER translocation site and promotes both the insertion of membrane proteins and the translocation of secretory proteins.

Endoplasmic Reticulum↗
PubMed1995

Drugs associated with drug-related deaths in Edinburgh and Glasgow, November 1990 to October 1992.

Between 1991 and 1992 there was a four-fold increase in drug-related deaths in Glasgow. Comparing records of the drug-related deaths for November 1990-October 1991 and November 1991-October 1992 in Edinburgh and Glasgow, it was found that the increase in Glasgow was statistically significant and that heroin, often mixed with other drugs, which most often included temazepam, diazepam and alcohol, was implicated in the increase in deaths in Glasgow. A number of the deceased had been prescribed temazepam or diazepam. Discussed are the hazards of drug mixing and the possibility that the use of buprenorphine by drug injectors previously had kept the number of overdoses relatively low.

Cross-Sectional Studies↗
PubMed1995

A combined approach to reduce mite allergen in the bedroom.

BACKGROUND: Asthma is a common chronic disease of childhood. House dust mite (HDM) are known to be a major source of allergen affecting atopic asthmatics. No single control method has been demonstrated to consistently reduce asthma. OBJECTIVE: We investigated the effect of a combination of two methods of HDM allergen control on HDM allergen content in the bedding and carpets of asthmatic children. METHODS: This was a double-blind placebo-controlled trial treating the bedrooms of 56 mite-sensitive asthmatic children. The carpet and the mattress, duvet and pillows (bedding) in the bedroom of children of the active group were treated with the acaricide Acarosan (benzyl benzoate). The bedding was then encased in vapour permeable waterproof fabric (Intervent--cotton coated with polyurethane) for 24 weeks. The carpet and bedding of the control group were treated with placebo and the bedding encased in cotton covers for 24 weeks. Dust samples were collected from all these items in a standard manner at regular intervals and Der p I content analysed. RESULTS: The group with active treatment had a median reduction of 480 ng (100%) in mite allergen from the mattress vs 215 ng (53%) reduction in placebo-treated group by 6 weeks. The Der p I content of the active group's bedding was always less than the placebo group after treatment (P < 0.01). The acaricide applied to the carpets or inside the mattress covers was ineffective in reducing allergen content. CONCLUSION: This study confirms the effectiveness of encasing covers in reducing the mite allergen exposure but indicates there is no further advantage in applying acaricide simultaneously.

Allergens↗
PubMed1995

Comparison of the number of vasopressin-producing hypothalamic neurons in rats and humans.

The aim of this study was to assess the number and proportion of vasopressin-producing neurons in the hypothalamic magnocellular nuclei in rats and humans. Accurate and unbiased neuronal counts were estimated using the optical disector method. Arginine vasopressin-containing neurons were immunohistochemically visualized in formalin-fixed tissue sections. The magnocellular neurons were similar in size and morphology in both species. While the human hypothalamus contained significantly more vasopressin-containing neurons compared with the rat (36-fold increase), the proportion of vasopressin-containing neurons between species was similar. In both species, the majority of supraoptic neurons contained vasopressin, however the proportion of vasopressin-containing neurons in the human paraventricular nucleus was double that of the rat (nearly a 100-fold increase in number). These results suggest that the paraventricular nucleus contributes significantly to the release of vasopressin from the posterior pituitary in humans, whereas in rats vasopressin is mainly released by supraoptic neurons.

Animals↗
PubMed1995

Drug abuse deaths in Glasgow in 1992--a retrospective study.

A survey of 62 drug deaths in Glasgow showed a wider age range than expected (16-49), a high male to female ratio (44:18) and, where mode of employment had been recorded, a high degree of unemployment (91%). The majority of deaths occurred near centres of known supply. Although a number occurred in the family home, a large proportion were not at the place of residence. In only two cases was morphine detected alone. The majority of the deaths were from combinations of drugs, primarily with benzodiazepines.

Adolescent↗
PubMed1995

[Aortic prosthetic endocarditis and periprosthetic abscess caused by Staphylococcus aureus].

Prosthetic endocarditis with annular abscess formation is a severe complication of cardiac valve replacement fortunately uncommon, though highly lethal. Increasing surgical experience and the high mortality with medical management have led to a widespread recommendation for early prosthetic replacement. We report a case of a 49 year old man with infective endocarditis due to Staphylococcus aureus in aortic ascendens prosthetic and aortic valve prosthetic complicated with periaortic abscess which was as successful treatment by drain of abscess without prosthetic replacement.

Abscess↗
PubMed1995

Delayed papillary muscle rupture following mild chest trauma.

A case of delayed papillary muscle rupture is reported, which developed 24 hours following a mild chest trauma. Transthoracic echocardiography established the diagnosis; immediate mitral valve replacement was carried out. The postoperative course was uneventful.

Accidental Falls↗
PubMed1995

Variable tissue reactions and endocrine responses to a jugular catheter.

Although the use of soft catheter materials allows for safe long-term venous access in humans and animals, a significant percentage of individuals react adversely. We have studied a group of 52 male rats over 30 days (d) for the category and degree of tissue responses to silicone-based catheters implanted in the jugular vein. Included in this evaluation was blood withdrawal at multiple intervals for assay of plasma hormones corticosterone (CORT) and prolactin (PRL) as they were correlated with the immune phenomena associated with early (5-7d) obstruction of the catheter tip. The intravascular portion of all catheters were covered with a transparent sheath which was composed of endothelial cells, smooth muscle cells, fibroblasts and numerous collagen fibers. Early blockage of catheters was the result of large white masses (wm) enclosing the tip which were continuous with the sheath. The wm consisted of: a) an inner zone nearest the catheter in some regions predominantly composed of numerous platelets and in others granulocytes and platelets; b) a middle zone containing numerous neutrophils; c) an outer zone containing a few inflammatory cells and many spaces filled with red blood cells. Rats that developed a wm blockage 7-10d after catheter placement had higher plasma CORT levels (3-5d post implant) when compared to those of animals with catheters remaining open 3-4 weeks. When viewed together, these observations describe a subset of a larger population of rats that have a local intravascular inflammatory reaction to silicone-based catheters. This preparation may be a useful model for investigating reported differences in human reactivity to silicone-based prostheses.

Animals↗
PubMed1995

Mitral annular calcification in CAPD patients with a low degree of hyperparathyroidism. An analysis of other possible risk factors.

Chronic renal failure has been suggested as a risk factor for mitral annular calcification (MAC), a degenerative process of the mitral annulus. The objective of the present study was to define MAC risk factors at the start of dialysis and 'de-novo' appearance after medium- or long-term CAPD, in a non-selected population (135 patients) with a low degree of secondary hyperparathyroidism. Echocardiographic studies were performed at the beginning of CAPD and every 1-1.5 years thereafter. Diagnosis of MAC was established by M mode and 2-D study. Seventeen of 135 patients studied at the start of dialysis showed MAC. Patients who showed MAC were older and presented a higher mean systolic blood pressure. The other anthropometric/demographic parameters did not show statistically significant differences. MAC thickness: mean 6.21 +/- 3.65 mm (range 3-17.2 mm). The posterior annulus was universally affected and in four patients the anterior annulus was involved. Seventeen of 76 patients included in the follow-up study developed MAC. No significant differences for demography, except age, with MAC patients being older, were found. Mean time on CAPD until de-novo MAC diagnosis was 49.7 +/- 26.9 months. MAC thickness: mean 4.97 +/- 1.6 mm (range 3-8.42 mm). The posterior annulus was affected in all patients except for one and in four patients the anterior annulus was involved. The most remarkable echocardiographic feature is the almost constant association of MAC with left atrial dilatation (LAD). The last one does not seem a consequence of mitral insufficiency, or systolic dysfunction. Left ventricular hypertrophy was universally found, with no different intensities for patients with or without MAC. In conclusion, a high incidence of mitral annular calcification has been found in CAPD patients. Our data do not confirm the role of classical invoked risk factors. Blood CaP product under 75, a moderate to mild degree of hyperparathyroidism and/or hypertension with left ventricular hypertrophy do not seem to be isolated risk factors during the CAPD period. Length of time on CAPD, for unknown reasons, seems to favour the appearance of MAC. At starting dialysis, high systolic blood pressure and left ventricular hypertrophy seem to be related to MAC. Diabetes appears to represent an additional risk factor. Further research on mitral annular calcification pathogenesis and its consequences is urgently required.

Calcinosis↗
PubMed1994

African-American factor VII-deficient variants in Georgia (FVII variants).

We studied African-American Factor (FVII)-deficient variants and carriers in Georgia by measuring their levels of FVII antigen (FVIIAG) and FVII procoagulant (FVIIC). Factor VIIAG was determined using enzyme-linked immunoassay (ELISA), whereas FVIIC was measured in two ways: 1) by fibrin clotting methods that employed human recombinant (HRFVIIC), human placental (HPFVIIC), rabbit brain (RBFVIIC), and bovine brain (BBFVIIC) thromboplastins; and 2) by an amidolytic method (AMFVIIC). Prothrombin time tests (PT) were also performed by standard methods. These 4 FVII-deficient patients and 3 carriers demonstrated the following results: PT: 18.2 +/- 6.5 sec; FVIIAG: 73.0 +/- 14.9%; HRFVIIC: 30.6 +/- 20.3%; HPFVIIC: 30.5 +/- 21.4%; RBFVIIC: 25.3 +/- 21.4%; BBFVIIC: 30.6 +/- 17.5%; AMFVIIC: 44.1 +/- 18.3%. We conclude that a group of clinically mild African-American FVII-deficient variants exists in Georgia. This group is characterized by the presence of FVIIAG and decreased FVIIC, using a variety of thromboplastins; and excellent correlation was noted for both human thromboplastins.

Antibodies↗
PubMed1994

Cellular and molecular abnormalities in the vascular endothelium of diabetes mellitus.

Diabetic vascular complications affect both micro- and macrovasculature, primarily in the retina, renal glomeruli, and multiple sites in the macrovessels. This review presents a summary of the abnormal function found in vivo and in cultured vascular cells exposed to elevated levels of glucose. We also discuss the various biochemical hypotheses that have been proposed to explain the adverse effects of hyperglycemia on vascular cells.

Diabetic Angiopathies↗
PubMed1994

Cardiac and plasma atrial natriuretic peptide after 9-day hindlimb suspension in rats.

To determine atrial natriuretic peptide (ANP) adaptation to simulated weightlessness, immunoreactive plasma (ir-NH2- and ir-COOH-terminals) and atrial (ir-COOH-terminal) ANP levels, atrial mRNA expression, immunoreactive cardiocyte ANP levels (ir-NH2- and ir-COOH-terminals), and ultrastructural observations of granules in atrial cardiocytes were assessed in male Wistar rats after a 9-day hindlimb suspension. Plasma ir-NH2- and ir-COOH-terminal ANP concentrations decreased by 17 (P < 0.05) and 37% (P < 0.05), respectively, in suspended rats. A concomitant ir-COOH-terminal ANP content reduction was also observed in left (31%; P < 0.01) and right atria (25%; P < 0.05). Atrial ANP mRNA expression was severely depleted in the right atrium and less so in the left atrium after 9 days of hindlimb suspension. Immunocytochemistry observations demonstrated lowered NH2- and COOH-terminal ANP immunoreactivities in left and right atria from suspended rats. A reduced number of storage granules (dense granules) in both atria was also noted on ultrastructural analysis. It was concluded that ANP biosynthesis, storage, and release were decreased after a 9-day hindlimb suspension.

Animals↗