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J Cox

Publications and source records attributed to J Cox.

At least 73 records · Page 4Linked to original sources
PubMed1999

The benefit of treatment intensification is age and histology-dependent in patients with locally advanced non-small cell lung cancer (NSCLC): a quality-adjusted survival analysis of radiation therapy oncology group (RTOG) chemoradiation studies.

PURPOSE: Currently, chemoradiation treatment strategies in locally advanced NSCLC are essentially the same irrespective of tumor histology or patient age. The purpose of this study is to analyze the impact of age, histology, Karnofsky performance status (KPS), and specific toxicities on the median survival time (MST) and quality-adjusted survival (QTime) for each treatment strategy. METHODS AND MATERIALS: Nine hundred seventy-nine patients with Stage II-IIIB inoperable NSCLC were enrolled on 6 prospective Phase II and III studies from 1983 to 1995. Treatment regimens ranged from standard RT (SRT) to 60 Gy, hyperfractionated RT (HRT) to 69.6 Gy, induction chemotherapy (ICT) of cisplatin (CIS) and vinblastine (VBL) followed by SRT, ICT + concurrent CT (CCT) + SRT, and CCT + HRT; CCT consisted of etoposide or VBL + CIS. Toxicities assessed were skin, mucous membrane, lung, esophagus, neurologic, hematologic, and upper GI. QTime was calculated by weighting the time spent with a specific toxicity, as well as local or distant tumor progression. Each toxicity was weighted with increasing severity as the toxicity increased in grade. RESULTS: As expected, patients with the worst KPS (50-70) had the lowest MST (7.8 months) and QTime (6.7 months). Patients <70 years had improved survival with more aggressive therapy (i.e., ICT + SRT or CCT + HRT), while patients > 70 years achieved the best QTime with standard RT (SRT) alone. In patients with squamous cell carcinoma, those treated with ICT + CCT + SRT had dramatically improved MST (25.7 months) and QTime (21.8 months) compared to the other treatment regimens (11.7-12.8 and 10.7-12 months, respectively). Patients with adenocarcinoma, however, generally manifested incrementally better MST and QTime as the therapies intensified. Within the concurrent chemoradiation arms, the upper GI and lung toxicities had the greatest impact on QTime. CONCLUSION: This quality-adjusted survival analysis suggests that there is a critical relationship between the type of histology and its optimal treatment, age and the ability to tolerate intensive therapy, and the need to reduce lung and upper GI toxicities.

Adenocarcinoma↗
PubMed1999

Effects of pregnancy and delivery on serum concentrations of Clara Cell Protein (CC16), an endogenous anticytokine: lower serum CC16 is related to postpartum depression

There is now some evidence that lower serum concentrations of Clara Cell Protein (CC16) are related to stress-induced anxiety, psychoses and major depression. This study was developed to determine whether serum CC16 is lowered in the early puerperium and whether Postnatal Depression and Postnatal Blues are associated with lower levels of serum CC16. Serum concentrations of CC16 were assayed in 17 non-pregnant women and in 98 pregnant women before delivery and 1 and 3 days after delivery. On each occasion the parturients completed the State version of the Spielberger State-Trait Anxiety Inventory (STAI) and the Zung Depression Rating Scale (ZDS). Serum CC16 was significantly lower in pregnant women, at the end of pregnancy as well as 1 and 3 days after delivery, than in the non-pregnant women. Serum CC16 was somewhat, although significantly, higher 1 and 3 days after delivery than before delivery. Parturients who developed a postpartum depression had significantly lower serum CC16 concentrations than women who did not. There were no significant differences in serum CC16 between the puerperal women whose STAI or ZDS scores increased in the puerperium and those whose scores did not. It is concluded that in puerperal women there is a decreased anti-inflammatory capacity in the serum, in part caused by lowered serum CC16, and that the latter may be related to the development of postpartum depression.

Journal Article↗
PubMed1999

Peptide based cytotoxic T-cell vaccines; delivery of multiple epitopes, help, memory and problems.

Synthetic CD8+ cytotoxic T-lymphocyte (CTL) peptide epitope based vaccines are being developed against a number of human diseases. Here we describe extensive preclinical testing of peptide epitope vaccines formulated with a protein as a source of CD4 help and Montanide ISA 720, an adjuvant currently in human clinical trials. Such water-in-oil formulations could effectively co-deliver several peptide epitopes and simultaneously induce multiple independent CTL responses. The efficiency of CTL induction by some peptides was, however, dependent on the aqueous buffer conditions, with poor performance correlating with non-covalent peptide oligomerisation. Any of a number of proteins currently used in human vaccines could supply CD4 help and no difference in CTL induction was obtained if the CD4 response was amnestic or a primary. Peptide immunisation was found to induce long term CTL memory and the recall of protective responses did not depend on an amnestic CD4 response. Slow pyroglutamic acid formation and rapid oxidation of methionine residues was observed in water-in-oil formulations, however, the latter had no effect on CTL induction. These data highlight the need to monitor for potential deleterious chemical events and interpeptide interactions, but illustrate that peptide based vaccination can effectively deliver multiple epitopes, in conjunction with any protein, and induce protective memory.

Adjuvants, Immunologic↗
PubMed1999

Say what you mean

Explore the source record for details and available documents.

Journal Article↗
PubMed1999

When the cradle falls: the treatment of postnatal depression in a psychiatric day hospital compared with routine primary care.

BACKGROUND: Postnatal depression affects one in ten women within 6 months of childbirth. The most effective treatment strategy for postnatal depression is not clear. METHODS: This prospective, naturalistic study of the treatment of postnatal depression compared 30 women treated at a specialised psychiatric day hospital with 30 women treated using routine primary care (RPC). Clinical, marital and social adjustment were assessed on three occasions over 6 months using: the Edinburgh Postnatal Depression Questionnaire (EPDS); the Clinical Interview schedule (CIS); the Anxiety Subscale of the Hospital Anxiety and Depression Scale; the Dyadic Adjustment Scale (DAS); and the Work Leisure and Family Life Questionnaire-Modified (WLFLQ-M). RESULTS: There were no significant differences between the two groups at baseline. However, there were significant differences in outcome at 3 and 6 months follow-up for all outcome measures except the DAS. At 6 month follow-up 21 of the PBDU group were no longer depressed compared with 7 of the RPC group. CONCLUSIONS: A specialised day hospital is a more effective treatment setting for postnatal depression than routine primary care. LIMITATIONS OF THE STUDY: The study is not an RCT, so systematic bias is possible. The sample size is relatively small and the duration of follow-up relatively short.

Adolescent↗
PubMed1999

bcl-2 and c-erbB-2 proteins are involved in the regulation of VEGF and of thymidine phosphorylase angiogenic activity in non-small-cell lung cancer.

Tumour angiogenesis has been recently recognised as one of the most important prognostic factors in lung cancer. Although a variety of angiogenic factors have been identified, the angiogenesis process remains poorly understood. Bcl-2, c-erbB-2 and p53 are well-known oncogenes involved in non-small-cell lung cancer pathogenesis. A direct correlation of thymidine phosphorylase (TP) and of vascular endothelial growth factor (VEGF) with intratumoural angiogenesis has been reported. In the present study we investigated the possible regulatory role of bcl-2, c-erB-2 proteins in angiogenesis and in VEGF and TP expression in non-small-cell lung cancer. Two hundred sixteen specimens from T1,2-N0,1 staged patients treated with surgery alone were immunohistochemically examined. Bcl-2 and c-erbB-2 were significantly inversely related to each other (P = 0.04) and both were inversely associated with microvessel density (P < 0.02). High TP and VEGF reactivity was statistically related to loss of bcl-2 expression (P < 0.01). A significant co-expression of c-erbB-2 with TP was noted (P = 0.01). However, TP expression was related to high angiogenesis only in cases with absence of c-erB-2 expression (P < 0.0001). c-erbB-2 expression in poorly vascularised tumours was linked with poor outcome (P = 0.03). The present study provides strong evidence that the bcl-2 gene has a suppressive function over genes involved in both angiogenesis (VEGF and TP) and cell migration (c-erbB-2) in NSCLC. TP and c-erbB-2 proteins are significantly, and often simultaneously, expressed in bcl-2 negative cases. However, expression of the c-erbB-2 abolishes the TP-related angiogenic activity. Whether this is a result of a direct activity of the c-erbB-2 protein or a consequence of a c-erbB-2-related immune response remains to be further investigated.

Aged↗
PubMed1999

A cross-cultural analysis of the use of the Edinburgh Post-Natal Depression Scale (EPDS) in health visiting practice.

This report describes a project that developed and undertook initial validation of a Punjabi version of the Edinburgh Post-Natal Depression Scale (EPDS). A multi-disciplinary and multi-ethnic project team translated the EPDS from English to Punjabi. A pilot study indicated a high level of correlation between the two scales opening the way for a larger study in which a total of 98 bi-lingual women completed both the English and Punjabi version of the scale 6-8 weeks after delivery of their child. Of these a further 52 completed the scales on a second occasion, 16-18 weeks post-partum. A small sub-group (n = 15) was subject to independent clinical assessment by a community psychiatric nurse (CPN) to determine their mental state, enabling the outcome of the assessment to be compared with the EPDS score. The scores of the English and Punjabi versions of the scale were analysed using Spearman correlation coefficient and the Bland Altman test. A high correlation was found between overall scores and most individual items on the scale. Furthermore, the independent assessment of mental health state indicated that a number of those women who scored 12 or above on the EPDS scale (the cut-off point for determining risk of post-natal depression (PND)) were diagnosed as having a post-natal depressive disorder by the CPN assessing them independently. Whilst the results to date are promising there is a need for further work to determine the validity, sensitivity and specificity of the Punjabi EPDS tool against international classification of depressive disorders and to establish optimal cut-off scores when using the Punjabi version of the EPDS.

Community Health Nursing↗
PubMed1999

Tyrosine phosphorylation modulates the interaction of calmodulin with its target proteins.

The activation of six target enzymes by calmodulin phosphorylated on Tyr99 (PCaM) and the binding affinities of their respective calmodulin binding domains were tested. The six enzymes were: myosin light chain kinase (MLCK), 3'-5'-cyclic nucleotide phosphodiesterase (PDE), plasma membrane (PM) Ca2+-ATPase, Ca2+-CaM dependent protein phosphatase 2B (calcineurin), neuronal nitric oxide synthase (NOS) and type II Ca2+-calmodulin dependent protein kinase (CaM kinase II). In general, tyrosine phosphorylation led to an increase in the activatory properties of calmodulin (CaM). For plasma membrane (PM) Ca2+-ATPase, PDE and CaM kinase II, the primary effect was a decrease in the concentration at which half maximal velocity was attained (Kact). In contrast, for calcineurin and NOS phosphorylation of CaM significantly increased the Vmax. For MLCK, however, neither Vmax nor Kact were affected by tyrosine phosphorylation. Direct determination by fluorescence techniques of the dissociation constants with synthetic peptides corresponding to the CaM-binding domain of the six analysed enzymes revealed that phosphorylation of Tyr99 on CaM generally increased its affinity for the peptides.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1999

Does an inflatable obstetric belt facilitate spontaneous vaginal delivery in nulliparae with epidural analgesia?

OBJECTIVE: To assess whether an inflatable obstetric belt, synchronised to apply uniform fundal pressure during a uterine contraction, reduces operative delivery rates when used in the second stage of labour. DESIGN: Randomised controlled trial. METHODS: Five hundred nulliparae with a singleton cephalic pregnancy at term and with an epidural in labour were recruited during the first stage and randomised at full dilatation. Standard care involved one hour passive second stage and one hour active pushing after which instrumental delivery was performed if delivery was not imminent. Those randomised to the belt group, in addition to standard care, had the inflatable obstetric belt for the whole second stage of labour. MAIN OUTCOME MEASURE: Mode of delivery. RESULTS: One hundred and eleven of the 260 women in the belt group (42.7%) compared with 94 of the 240 in the control group (39.2%) had a spontaneous vertex delivery (P = 0.423). The lift-out instrumental delivery rate was similar between the two groups: 108 belts (41.5%), compared with 101 controls (42.1%) (P = 0.902), whereas rotational instrumental deliveries in the belt group were 26 belts (10%) compared with 36 controls (15%) (P = 0.09). Fifteen women (5.8%) in the belt group and nine women (3.8%) in the control group had a caesarean section in the second stage (P = 0.292). An intact perineum was more likely in the belt group (16.5% compared with 9.6%, P = 0.022) as was a third degree tear (6.5% compared with 0.4%, P = 0.001). CONCLUSION: The inflatable obstetric belt did not significantly reduce operative delivery rates when used in this clinical setting in the second stage of labour.

Adult↗
PubMed1998

A quantitative mannose 6-phosphate receptor-based in vitro assay for recombinant human N-acetylgalactosamine-4-sulfatase.

An assay was developed, using two similar formats, to simultaneously measure both the lysosomal targeting receptor binding and enzyme activity of the recombinant human enzyme N-acetylgalactosamine-4-sulfatase. This assay also has potential application for all phosphorylated lysosomal enzymes that contain mannose-6-phosphate residues. The receptor was either purified from fetal bovine sera then adsorbed, or produced in situ by growing and fixing diploid human fibroblast-like cells, to a solid phase. The enzyme substrate was 4-methylumbelliferyl sulfate which fluoresces after cleavage of the sulfate moiety. Both the precursor and mature forms of the recombinant enzyme were used to demonstrate the specificity and usefulness of the assay. The assay is rapid and sensitive and has a wide dynamic range. Association between the receptor and the mannose-6-phosphate residues was abrogated in the presence of a competitive inhibitor, mannose 6-phosphate. However, partial activity was still measured when the mature enzyme was incubated in the presence of mannose 6-phosphate when using the fixed fibroblast format. This would indicate that the recombinant enzymes contain at least one terminal sugar moiety other than mannose 6-phosphate which can recognize receptors on the surface of human fibroblast-like cells. Other possible applications of this assay are also discussed.

Adsorption↗
PubMed1998

Phosphorylation of calmodulin alters its potency as an activator of target enzymes.

Previous work has shown that calmodulin (CaM) is constitutively phosphorylated in rat liver, probably by casein kinase II [Quadroni, M., James, P., and Carafoli, E. (1994) J. Biol. Chem. 269, 16116-16122]. A procedure is now described for the isolation of the phosphorylated forms of calmodulin (PCaM) free from CaM, since in vitro phosphorylation experiments yield a 50:50 mixture of 3-4 times phosphorylated CaM and native CaM. The activation of six target enzymes by PCaM was tested: myosin light chain kinase, 3',5'-cyclic nucleotide phosphodiesterase, plasma membrane Ca2+-ATPase, Ca2+-CaM-dependent protein phosphatase 2B (calcineurin), neuronal nitric oxide synthase, and CaM-kinase II. In general, the phosphorylation of CaM caused a decrease in enzyme binding affinity, increasing the Kact by 2-4-fold for MLCK, PDE, PM Ca2+-ATPase, and calcineurin. The Vmax at saturating concentrations of PCaM was less affected, with the exception of CaM-kinase II, which was only minimally activated by PCaM and NOS whose Vmax was increased 2.6 times by PCaM with respect to CaM. Phosphorylation of calmodulin had very little effect on the binding of calcium to the enzyme despite the fact that Ser 101 which is phosphorylated is located in the third calcium binding loop. CD measurements performed on CaM and PCaM indicated that phosphorylation causes a marked decrease in the alpha-helical content of the protein. Phosphorylated CaM is very prone to dephosphorylation and was thus tested as a substrate for several phosphatases. It was unaffected by calcineurin (PP2B), but was a reasonable substrate for the pleiotropic phosphatases PP1gamma and PP2A.

Animals↗
PubMed1998

A two-dose hepatitis B vaccine regimen: proof of priming and memory responses in young adults.

This study shows that two doses of a recombinant hepatitis B vaccine (10 micrograms or 20 micrograms of HBsAg per dose), administered 6 months apart to young, healthy adults, can induce an antibody (anti-HBs) response similar to that expected with the standard three-dose regimen of this vaccine given at intervals of 0, 1, and 6 months. While only 46-67% of the vaccinees displayed a protective anti-HBs titer of > or = 10 mIU ml-1 prior to the receipt of the second dose at 6 months, virtually all were primed as 97-99% of the subjects developed such a titer when tested a month after the second dose. Among vaccinees given 10 or 20 microgram doses, respectively, the secondary rise in antibody following the second dose yielded geometric mean titers (GMTs) of 1103 and 2538 mIU ml-1, respectively. The study further demonstrated that a two-dose regimen of vaccination induced strong immunologic memory for HBsAg, as a booster dose of vaccine given 2 years later resulted in a rapid and vigorous anamnestic antibody response.

Adolescent↗
PubMed1998

Studies on experimental adjuvanted influenza vaccines: comparison of immune stimulating complexes (Iscoms) and oil-in-water vaccines.

Detergent-disrupted influenza virus vaccines, formulated as Iscoms, or oil-in-water (o/w) emulsions, were administered parenterally to mice and evaluated for immunogenicity and protective efficacy. Both formulations enhanced both primary and secondary serum antibody responses. The magnitude of these responses with o/w emulsions was further enhanced by the addition of the non-ionic block copolymer L121 in the emulsion. Four weeks after primary immunization, mice were challenged by exposure to an aerosol containing infectious virus. Resistance to challenge in terms of survival rate and weight change correlated well with serum antibody titre for all formulations. Two major differences were observed between the adjuvant formulations. Iscom vaccines, formulated with Quil-A or the less toxic Quillaia saponin preparation Iscoprep 703, induced specific cytotoxic T-lymphocyte responses, whereas the o/w-based vaccines did not. In addition, dose-site reactivity studies in sheep showed that Iscom vaccines were less reactive than o/w-based vaccines, the degree of reactivity of the latter increasing sharply with increasing L121 concentration. On the basis of these studies, Iscoms were chosen for development as a potential adjuvant for human influenza vaccines.

Adjuvants, Immunologic↗