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Biomedical subjects

L Jones

Publications and source records attributed to L Jones.

At least 91 records · Page 5Linked to original sources
PubMed2000

Hormonal and other factors in relation to survival among breast cancer patients.

We have examined the relationship between all-cause mortality and various hormonal and other factors in over 1,200 women with breast cancer recruited into 2 consecutive case-control studies between 1969 and 1984. The age at diagnosis ranged from 24 to 59 years, and the majority (74%) were pre-menopausal at diagnosis. Analyses were based on follow-up to 1 January 1994, by which time 608 (50%) of the women had died. Of the factors examined, weight was most strongly associated with survival, with a significant increase in the risk of death with increasing weight. Two hormonal factors, time since last birth and time since last oral contraceptive use, were also independently associated with survival. All of these associations remained after adjustment for stage and histological nodal status. Our findings provide new evidence to suggest that reproductive factors and exogenous hormones in the form of oral contraceptives may influence survival in women with breast cancer, even after differences in stage and nodal status have been taken into account.

Adult↗
PubMed2000

Characterization of fungal spores by laser desorption/ionization time-of-flight mass spectrometry.

A considerable volume of research has now been completed on the application of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) to the analysis of bacteria; however, to date no definitive studies have been made using this technique on fungi. Preliminary studies on the application of the MALDI-MS methodology, previously developed for the analysis of bacteria, to the analysis of intact fungal spores are described here. MALDI-MS and electrospray mass spectrometry enable the high molecular weight analysis of proteins, glycoproteins, oligosaccharides and oligonucleotides. Using MALDI-MS with bacteria has demonstrated the ability to produce 'fingerprints' of the intact cells with the ions observed being associated with the proteinaceous components of the cell wall. This paper reports the adaptation of this technique to the direct analysis of fungal cells. The high percentage of carbohydrate in the fungal cell wall indicates that the ions observed in the mass spectrometric experiments may be of carbohydrate origin. Penicillium spp., Scytalidium dimidiatum and Trichophyton rubrum have been studied in this preliminary investigation and all show individually distinctive spectra which would appear to provide a profile of the cellular material with discrete peaks being observed over the mass range 2 to 13 kDa. The spectra obtained are reproducible within the method used but, as shown in our previous studies on bacteria, washing may selectively release components from the fungal cell wall.

Carbohydrates↗
PubMed2000

Constituents of Cassia laevigata.

Calendin (1), cinnamic acid (2), 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-propan-1-one (3), 2,3-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)-propan-1-one (4), 3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-propan-1-one (5), syringic acid (6) and vanillic acid (7) have been isolated from a dichloromethane extract of the leaves and branches of Cassia laevigata.

Humans↗
PubMed2000

Counselling: filling a gap in general practice.

A counsellor worked for 1 year in three practices in a rural area where there was previously no practice-based counselling. The service was evaluated, using a range of methods, in order to inform general practitioners and policy-makers about the demand for counselling, where it fits with other services, its potential value and how to organise and audit the service efficiently. Five kinds of information were collected: administrative data; patients' views; well-being scores; GPs' perceptions of individual patients; and interviews with the counsellor, GPs and other primary care staff by an independent researcher. All the GPs used the service, referring 131 people. The most common reason for referral was 'relationship difficulties'. There were improvements in patients' well-being, self-awareness and coping skills, and high satisfaction among GPs and patients. Communication with other services was seen to improve. The counselling service was found to fill a gap by addressing the needs of a substantial group of patients for whom psychiatric care was inappropriate.

Attitude of Health Personnel↗
PubMed2000

Enhanced safety and efficacy of live attenuated SIV vaccines by prevaccination with recombinant vaccines.

The only vaccines shown to be protective against intravenous challenge with virulent virus in the simian immunodeficiency virus (SIV)/macaque model are attenuated live SIVs. However, these vaccines have several disadvantages: 1) they persist indefinitely in vaccinated macaques; 2) they are pathogenic to neonatal macaques; and 3) they are lethal in some adult macaques. To enhance the safety and efficacy of these vaccines, we immunized macaques first with recombinant vaccines and then inoculated the animals with SIV(delta(nef)). In the first experiment, preimmunized macaques advanced to disease slower than controls after challenge with virulent SIV; five animals survived for 3 years without disease and only the vaccine virus (SIV(delta(nef)) could be isolated at this time. In the second experiment, preimmunized animals had lower virus loads and no disease compared to controls.

Animals↗
PubMed2000

Comparative sequencing of the proneurotensin gene and association studies in schizophrenia.

Neurotensin (NT) is an endogenous tridecapetide1 cleaved from a precursor proneurotensin/ proneuromedin protein. NT localises within dopaminergic neurones in the mesocortical, mesolimbic and nigrostriatal systems1-3 and it is now clear that NT can selectively modulate dopaminergic neurotransmission.2-9 These anatomical and functional connections have led to the hypothesis that NT dysfunction might contribute to the pathogenesis of neuropsychiatric disorders in which disordered dopaminergic neurotransmission is suspected, particularly schizophrenia.3 The latter hypothesis has been supported circumstantially by the observation that central administration of NT produces effects similar to those produced by the peripheral administration of atypical antipsychotics,10,11 and more directly by studies showing levels of NT in cerebral spinal fluid (CSF) is lower in schizophrenics than in controls.12,13 To allow such hypotheses to be tested, we used denaturing high performance liquid chromatography (DHPLC)14 to identify three sequence variants in the neurotensin gene (NTS) that might alter NT structure or expression. However, using a case-control study design and a novel genotyping system based upon a primer extension protocol and HPLC detection,15 we found no evidence to support the hypothesis that variation in the proneurotensin gene contributes to susceptibility to schizophrenia.

Alleles↗
PubMed2000

Comparative sequencing and association studies of aromatic L-amino acid decarboxylase in schizophrenia and bipolar disorder.

Aromatic L-amino acid decarboxylase (AADC) is a relatively non specific enzyme involved in the biosynthesis of several classical neurotransmitters including dopamine and 5-hydroxytryptamine (5HT; serotonin). AADC does not catalyse the rate limiting step in either pathway, but is rate limiting in the synthesis of 2-phenylethylamine (2PE) which is a positive modulator of dopaminergic transmission and a candidate natural psychotogenic compound.1 We and others have proposed that polymorphism in AADC resulting in altered 2PE activity might contribute to the pathogenesis of psychosis. In order to test this hypothesis, we have used denaturing high performance liquid chromatography (DHPLC)3 to screen 3943 bases of the AADC gene and its promoter regions for variants that might affect protein structure or expression in 15 unrelated people with schizophrenia, and 15 unrelated people with bipolar disorder. Three polymorphisms were identified by DHPLC: a insertion/deletion polymorphism in the 5' UTR of the neuronal specific mRNA (g.-33-30delAGAG, bases 586-589 of GenBank M77828), a T>A variant in the non-neuronal exon 1 (g. -67T>A, GenBank M88070), and a G>A polymorphism within intron 8 (g. IVS8 +75G>A, GenBank M84598). Case-control analysis did not suggest that genetic polymorphism in the AADC gene is associated with liability for developing schizophrenia or bipolar disorder.

Aromatic-L-Amino-Acid Decarboxylases↗
PubMed2000

The high affinity neurotensin receptor gene (NTSR1): comparative sequencing and association studies in schizophrenia.

Neurotensin and its high affinity receptor (NTSR1) localise within dopaminergic neurones in the mesocortical, mesolimbic and nigrostriatal systems and it is now clear that neurotensin can selectively modulate dopaminergic neurotransmission. This has led to the hypothesis that altered neurotensin function contributes to the pathogenesis of schizophrenia and other psychoses. This hypothesis has been supported circumstantially by a number of lines of evidence. (1) Central administration of neurotensin produces effects similar to those produced by the peripheral administration of atypical antipsychotics. (2) Observations of low levels of neurotensin in the CSF of schizophrenics. (3) Reduced numbers of neurotensin receptors in the brains of schizophrenics. Given the above link between neurotensin and dopamine, and the evidence implicating altered neurotensin function in psychosis, we have postulated that DNA sequence variation in neurotensin or its receptors might be associated with schizophrenia. In keeping with this hypothesis, an association has recently been reported between schizophrenia and the gene encoding the neurotensin high affinity receptor (NTSR1). However, caution is required because the associated marker, a tetranucleotide repeat, is located 3 kb away from the 3' end of the gene and there is no evidence that it is functional. Therefore, as a follow-up to our earlier work on neurotensin, we have now sought to test the hypothesis that DNA sequence variants that alter the structure or expression of the NTSR1 gene (VAPSEs) are associated with schizophrenia. However, while we found 14 novel sequence variants in 28 probands with psychosis, none resulted in an amino acid change, and neither direct nor indirect association studies suggested these are involved in susceptibility to schizophrenia.

Brain Chemistry↗
PubMed2000

The use of real-time quantitative polymerase chain reaction and comparative genomic hybridization to identify amplification of the REL gene in follicular lymphoma.

Using comparative genomic hybridization (CGH), aberrations in DNA copy number were studied before and after transformation of follicular lymphoma to diffuse large B-cell lymphoma in six patients (15 lymph node biopsies in total). The most common and also the most discrete and intense amplification occurring in four out of 15 biopsies from three different patients was of 2p13-16. Using real-time quantitative polymerase chain reaction (RQ-PCR), REL amplification was found to be implicated at this locus. This technique also identified amplified REL in a further two biopsies, presumably below the detection level of CGH. REL amplification was quantified by comparing it, in most cases, with three endogenous reference genes, albumin, beta2-microglobulin and CD8alpha, that lie close to REL on 2p. There was no correlation apparent between 2p13-16 amplification or REL amplification and transformation. This study shows the usefulness of coupling CGH, for detecting recurring abnormalities, with the real-time PCR technique for rapid gene dosage quantification and confirms that the REL gene is a potential candidate in the pathogenesis of a particular subset of follicular lymphomas.

DNA Primers↗
PubMed2000

Laboratory findings associated with thrombophilia are not more common in inflammatory bowel disease.

Thromboembolic disease (TED) has been recognized as a complication of inflammatory bowel disease (IBD) since the 1930s (Bargen & Barker 1936). The relative contributions of inherited or acquired thrombophilia and the inflammatory response to the mechanism of this tendency is unclear. Thrombotic events are more common in active disease although significant numbers also occur spontaneously, when the disease is in clinical remission (Talbot et al. 1986; Jackson et al. 1997). Studies looking at the prevalence of specific thrombophilic states such as Antithrombin III deficiency (Jackson et al. 1997; Lake, Stauffer & Stuart 1978; Cianco et al. 1996; Ghosh et al. 1983), Factor V Leiden mutation (APC Resistance) (Jackson et al. 1997; Probert et al. 1997; Ardizzone et al. 1998; Liebman et al. 1998), anticardiolipin antibodies (Ciancio et al. 1996), Protein C (Wyshock, Caldwell & Crowley 1988; Korsten & Reis 1992) and Protein S deficiencies (Jorens et al. 1990; Aadland et al. 1992) in IBD have been contradictory or equivocal. We had previously found that IBD patients with a history of TED are not more likely to have a laboratory thrombophilic abnormality than those with uncomplicated disease. We also demonstrated that the prevalence of heterogenous laboratory thrombophilic abnormalities (usually minor) in all IBD patients may be as high as 60%, much higher than the recognized prevalence of TED (Lim, Jones & Gould 1996). We wondered how this would compare with the healthy non-IBD population. We have therefore explored the prevalence of such thrombophilic abnormalities in a group of IBD patients who had no history of TED and compared them with healthy age and sex matched controls.

Adult↗
PubMed2000

Are p53 and MIB-1 overexpressed in cholesteatoma?

INTRODUCTION: There is controversy regarding the expression of p53 and MIB-1 in cholesteatoma.1 This study was instituted to study this. p53 is an intracellular protein which plays a critical role in control of the cell cycle at the G1 check point. MIB-1 is recognized as a marker of cellular proliferation. Using deep meatal skin controls, the question addressed was, 'are p52 and MIB-1 overexpressed in cholesteatoma'? METHOD: Immunocytochemistry using the avidin-biotin technique on frozen tissue sections with primary antibody to p53 (n = 17, controls = 17) and MIB (n = 17, controls = 7) was performed on cholesteatoma and deep meatal skin control specimens. Appropriate positive and negative controls were employed for each antibody. Slides were analysed in a blind fashion by two independent observers. Statistical analysis was performed using the Mann-Whitney test. RESULTS: Expression of p53 was minimal or absent in both cholesteatoma and controls. No significant difference in p53 expression was found between the two groups (P = 0.02). MIB-1 expression was higher in cholesteatoma than in controls, although this was not statistically significant (P = 0.09). CONCLUSION: This study did not demonstrate an increased expression of p53 cholesteatoma, indicating no evidence of a dysfunctional cell cycle. MIB-1 results showed a possible trend towards significance, which requires a more powerful study to evaluate this further. The probability that there is an increased rate of cellular proliferation in cholesteatoma, when compared to deep meatal skin controls, cannot be excluded.

Journal Article↗
PubMed2000

Epithelial inclusions in association with mucin ball development in high-oxygen permeability hydrogel lenses.

Debris trapped behind contact lenses may be associated with adverse reactions in extended wear. Although streaks and clumps of cellular material have been reported after overnight wear of conventional materials, recent experience with several high-oxygen permeability (Dk), silicone-containing hydrogel lenses indicates that certain participants are prone to the development of a unique back surface debris. This debris forms as spherical, translucent entities and results in depressions within the ocular surface after lens removal. Little information is known about these spherical bodies, particularly with respect to their composition and development. In this report, we provide photographic evidence of this debris (sometimes termed "mucin balls" or "lipid plugs"), discuss its differential diagnosis and describe a case in which material seems to be embedded in the epithelium as a direct consequence of their presence.

Adult↗
PubMed2000

An in vivo comparison of the kinetics of protein and lipid deposition on group II and group IV frequent-replacement contact lenses.

PURPOSE: To investigate the degree and rate of deposition of protein and lipid on FDA group II and group IV contact lens materials over a period of up to 28 days of wear. METHODS: Twenty-two subjects wore a group IV lens (Acuvue) and a group II lens (Soflens 66) in a randomized, cross-over study. The lenses were randomly worn for periods between 1 and 28 days and then collected for laboratory-based deposition analysis. RESULTS: The group II lenses revealed an increased degree of lipoidal spoilage (p < 0.0001) and the group IV lenses exhibited increased protein spoilage (p < 0.0001). Surface protein for both materials reached a maximum after 1 day and did not increase over the 4-week wearing period (p = NS). Total protein for group IV lenses reached a maximum between 1 and 7 days and then reached a plateau, with no further increase occurring (p = NS), whereas total protein accumulation on the group II lens continued to increase across all time periods (p < 0.05). Lipid deposition on the group IV lens was maximal after 1 day and increased no further (p = NS), whereas lipid deposition on the group II material monotonously increased and progressively built-up over the 4 weeks of wear (p < 0.0001). CONCLUSIONS: The kinetics of contact lens deposition is mediated by the chemical structure of the contact lens material under consideration. Protein deposition occurs rapidly with group IV materials before reaching a maximum, whereas N-vinyl pyrrolidone-containing group II materials progressively accumulate protein and lipid deposits, with no plateau occurring.

Adult↗
PubMed2000

Respiratory syncytial virus G and/or SH glycoproteins modify CC and CXC chemokine mRNA expression in the BALB/c mouse.

Chemokine mRNA expression by pulmonary leukocytes following infection of BALB/c mice with two strains of respiratory syncytial virus (RSV) and one strain of parainfluenza virus type 3 (PIV-3) was determined. The results suggest that RSV G and/or SH proteins inhibit early MIP-1alpha, MIP-1beta, MIP-2, MCP-1, and IP-10 mRNA expression. TCA-3 mRNA expression was found to be increased during PIV-3 infection.

Animals↗
PubMed2000

Increased matrix metalloproteinase-9 activity in unstable carotid plaques. A potential role in acute plaque disruption.

BACKGROUND AND PURPOSE: Acute disruption of atherosclerotic plaques precedes the onset of clinical syndromes, and studies have implicated a role for matrix metalloproteinases (MMPs) in this process. The aim of this study was to establish the character, level, and expression of MMPs in carotid plaques and to correlate this with clinical status, cerebral embolization, and histology. METHODS: Plaques were obtained from 75 consecutive patients undergoing carotid endarterectomy and divided into 4 groups according to symptomatology (group 1, asymptomatic; group 2, symptomatic >6 months before surgery; group 3, symptomatic within 1 to 6 months; group 4, symptomatic within 1 month). All patients underwent preoperative and intraoperative transcranial Doppler monitoring. Plaques were subjected to histological examination and quantification of MMPs by zymography and ELISA. RESULTS: The level of MMP-9 was significantly higher in group 4 (median 125.7 ng/mL for group 4, median <32 ng/mL for all other groups; P=0.003), with no difference in the levels of MMPs 1, 2, or 3. Furthermore, the MMP-9 concentration was significantly higher in plaques undergoing spontaneous embolization (P=0.019) and those with histological evidence of plaque instability (P<0.03). In situ hybridization demonstrated increased MMP-9 expression in highly symptomatic plaques in areas of intense inflammatory infiltrate. CONCLUSIONS: The concentration, production, and expression of MMP-9 is significantly higher in unstable carotid plaques. If this proves to be a causal relationship, MMP-9 may be a strong candidate for pharmacotherapy aimed at stabilizing plaques and preventing stroke.

Aged↗
PubMed2000

Medical complications after stroke: a multicenter study.

BACKGROUND AND PURPOSE: This prospective, multicenter study was performed to determine the frequency of symptomatic complications up to 30 months after stroke using prespecified definitions of complications. METHODS: We recruited 311 consecutive stroke patients admitted to hospital. Research nurses reviewed their progress on a weekly basis until hospital discharge and again at 6, 18, and 30 months after stroke. RESULTS: Complications during hospital admission were recorded in 265 (85%) of stroke patients. Specific complications were as follows: neurological-recurrent stroke (9% of patients), epileptic seizure (3%); infections-urinary tract infection (24%), chest infection (22%), others (19%); mobility related-falls (25%), falls with serious injury (5%), pressure sores (21%); thromboembolism-deep venous thrombosis (2%), pulmonary embolism (1%); pain-shoulder pain (9%), other pain (34%); and psychological-depression (16%), anxiety (14%), emotionalism (12%), and confusion (56%). During follow-up, infections, falls, "blackouts, " pain, and symptoms of depression and anxiety remained common. Complications were observed across all 3 hospital sites, and their frequency was related to patient dependency and duration after stroke. CONCLUSIONS: Our prospective cohort study has confirmed that poststroke complications, particularly infections and falls, are common. However, we have also identified complications relating to pain and cognitive or affective symptoms that are potentially preventable and may previously have been underestimated.

Accidental Falls↗
PubMed2000

Group therapy program for African-American veterans with posttraumatic stress disorder.

A Vet Center's group therapy treatment program for African-American veterans with posttraumatic stress disorder (PTSD) has met regularly and expanded since it was established in 1984. Program attributes described by participants as particularly helpful include facilitating open communication of thoughts and feelings among African-American men; providing support for coping with the intrapsychic, social, and economic effects of racism; increasing knowledge about the causes, consequences, and treatment of PTSD; and decreasing emotional and social isolation. The program appears to be a useful treatment for African-American veterans with PTSD.

Adaptation, Psychological↗