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Biomedical subjects

N Day

Publications and source records attributed to N Day.

At least 55 records · Page 3Linked to original sources
PubMed1999

Synthesis and characterization of a series of novel glutamic gamma-15N-anilide dipeptides.

The preparation of a series of novel Cbz-Gln-Gly dipeptide derivatives is reported, wherein the gamma-carboxamide groups of the glutamine side chains have been modified to gamma-15N-anilides which are substituted in the para position with -NO2, -Cl, -H, -CH3, -OCH3, and -N(CH3)2. Characterization of the free anilines (p(kappa)a values and 15N NMR chemical shifts) and corresponding gamma-anilides (15N NMR chemical shifts and FTIR wavenumbers) is also reported. Correlation of these physicochemical data to Hammett substituent parameters ((sigma)para) is discussed. These novel dipeptide derivatives should prove to be generally useful for structure-function enzymology studies of gamma-glutamyl transferring enzymes.

Anilides↗
PubMed1999

High-risk mammographic parenchymal patterns and anthropometric measures: a case-control study.

Mammographic parenchymal patterns are related to breast cancer risk and are also affected by anthropometric measure. We carried out a case-control study comprising 200 cases with high-risk (P2 and DY) mammographic parenchymal pattern and 200 controls with low-risk (N1 and P1) patterns in order to investigate the effect of body size and shape and breast size on mammographic patterns. Women in the highest quartile of body mass index (BMI) distribution were significantly less likely to have a high-risk pattern (odds ratio (OR) = 0.21, 95% confidence interval (CI) 0.08-0.52, P-value for trend = 0.001) compared to those in the lowest quartile. Relative to women with a waist to hip ratio (WHR) of less than 0.75, the OR of having a high-risk pattern in women with a WHR greater than 0.80 was 0.30 (95% CI 0.14-0.63). Breast size as measured by cup size was significantly and negatively related to high-risk pattern. Our study indicates that both BMI and WHR are negatively associated with high-risk patterns. However, both phenomena are associated with increased risk of breast cancer in postmenopausal women. This negative confounding of two positive risk factors means that the effect of parenchymal patterns on risk will tend to be underestimated when not adjusted for BMI and WHR and vice versa. Thus we may have underestimated the importance of BMI and mammographic parenchymal patterns in the past. Further studies are needed to determine a measure of parenchymal density that is independent of anthropometric measures and breast size.

Aged↗
PubMed1999

Evidence of blood-brain barrier dysfunction in human cerebral malaria.

Patients infected with the malaria parasite Plasmodium falciparum may develop a diffuse reversible encephalopathy, termed cerebral malaria. It is unclear how the intraerythrocytic parasite, which sequesters in the cerebral microvasculature but does not enter the brain parenchyma, induces this neurological syndrome. Adhesion of parasitized red blood cells in the brain microvasculature is mediated by specific receptors on the host endothelium, including intercellular adhesion molecule (ICAM)-1, CD36 and CD31. Leucocyte binding to cerebral endothelial cells in culture induces intracellular signalling via ICAM-1. The hypothesis that parasitized red blood cells binding to receptors on cerebral endothelial cells causes changes in the integrity of the blood-brain barrier was tested. Immunohistochemistry was used to examine the blood-brain barrier in human cerebral malaria, with antibodies to macrophage and endothelial activation markers, intercellular junction proteins, and plasma proteins. The distribution of the cell junction proteins occludin, vinculin and ZO-1 were altered in cerebral malaria cases compared to controls. While fibrinogen was the only plasma protein detected in the perivascular space, there was widespread perivascular macrophage activation, suggesting that these cells had been exposed to plasma proteins. It was concluded that functional changes to the blood-brain barrier occur in cerebral malaria, possibly as a result of the binding of parasitized red blood cells to cerebral endothelial cells. These changes require further examination in vitro.

Adolescent↗
PubMed1999

An mRNA stability complex functions with poly(A)-binding protein to stabilize mRNA in vitro.

The stable globin mRNAs provide an ideal system for studying the mechanism governing mammalian mRNA turnover. alpha-Globin mRNA stability is dictated by sequences in the 3' untranslated region (3'UTR) which form a specific ribonucleoprotein complex (alpha-complex) whose presence correlates with mRNA stability. One of the major protein components within this complex is a family of two polycytidylate-binding proteins, alphaCP1 and alphaCP2. Using an in vitro-transcribed and polyadenylated alpha-globin 3'UTR, we have devised an in vitro mRNA decay assay which reproduces the alpha-complex-dependent mRNA stability observed in cells. Incubation of the RNA with erythroleukemia K562 cytosolic extract results in deadenylation with distinct intermediates containing a periodicity of approximately 30 nucleotides, which is consistent with the binding of poly(A)-binding protein (PABP) monomers. Disruption of the alpha-complex by sequestration of alphaCP1 and alphaCP2 enhances deadenylation and decay of the mRNA, while reconstitution of the alpha-complex stabilizes the mRNA. Similarly, PABP is also essential for the stability of mRNA in vitro, since rapid deadenylation resulted upon its depletion. An RNA-dependent interaction between alphaCP1 and alphaCP2 with PABP suggests that the alpha-complex can directly interact with PABP. Therefore, the alpha-complex is an mRNA stability complex in vitro which could function at least in part by interacting with PABP.

3' Untranslated Regions↗
PubMed1999

Implementation of screening as a public health policy: issues in design and evaluation.

OBJECTIVE: To propose principles of design and measures of effect for cancer screening as a public health policy. MATERIAL: Finnish routine screening programme with mammography. DESIGN: Evaluation of mortality from breast cancer by before-after time trends among Finnish women, by geographical (by municipalities) comparisons, and by intention to screen at an individual level with individual controls who were cluster randomised and matched for age. OUTCOME MEASURES: Standardised mortality ratios (SMRs) from breast cancer (total), SMRs from breast cancers diagnosed during the screening programme (refined), deaths prevented, prolongation of life for each breast cancer detected, for each death prevented, for each compliant woman, for each screen, and for each invitation. Relative prolongation of life--that is, time gained versus time spent. RESULTS: SMRs only at an individual level with deaths from cancers diagnosed during the screening programme and individually selected controls showed 24% protection, whereas the other SMR measures were too crude or biased because of dilution and selection. Prolongation of life varied from 15 years for each death prevented to two days for each woman screened, with approximation for the prolongation relative to time spent of 3 to 1. CONCLUSIONS: A public health policy should be introduced gradually. Those not covered immediately by the policy serve as controls and they should be randomly allocated. The most relevant outcome measure is prolongation of life, and for public health purposes it should be given per unit of intervention, such as screen or invitation, and also related to the time spent for the intervention. Such gains are often small in a Western society, which implies that medicine, including research, should focus more on other aspects of life than length.

Adult↗
PubMed1999

Observed behaviors of patients with probable Alzheimer's disease who are hospitalized for diagnostic tests.

This study examines observed behaviors of hospitalized patients with probable Alzheimer's disease (AD) undergoing invasive diagnostic procedures. Data was obtained from nursing documentation in the medical records of 30 patients, 10 in each stage of AD (i.e., mild, moderate, severe). In general, analysis of the data revealed that changes in behavior occurred immediately prior to, during, and following these procedures. Specifically, the moderately impaired patients showed the most significant curve over the 5-day observation period, while patients in the mildly impaired group showed a high peak of behavioral change on the test day. The severely impaired group of patients had a higher sustained level of activity throughout the 5-day period. Routine assessment of the patients' usual behaviors, care-givers' knowledge of the stage of disease, and awareness of the potential impact that diagnostics may have on cognitively impaired patients could help care providers decide what interventions most likely would lead to successful outcomes.

Aged↗
PubMed1998

Breast cancer in East Anglia: the impact of the breast screening programme on stage at diagnosis.

OBJECTIVES: To assess the impact of the National Health Service breast screening programme on overall and stage-specific incidence of breast cancer in East Anglia; also, to predict the magnitude of the screening induced reduction in breast cancer mortality. SETTING: Women resident in East Anglia aged 50-69, diagnosed between 1976 and 1995. METHODS: Comparison of numbers and incidence of breast cancer by age, stage, and mode of detection; investigation of relative contributions of advanced (stages II, III, and IV) cancers to total incidence by detection mode; estimation of the reduction in advanced cancer incidence. RESULTS: There has been a large increase in early stage incidence in the age group 50-64 targeted by the screening programme. By 1995, the estimated decrease in advanced cancer incidence was between 7 and 19%. In 1995, of all breast cancers arising in the age group 50-69 years, 33% were screen detected, 27% were interval cancers, 15% were in non-attenders, 9% were in lapsed attenders, 7% occurred before invitation, and 4% arose in women outside the birth year range for invitation. Of the advanced cancers diagnosed in 1995, 31% were interval cancers, 20% were screen detected, 19% were in non-attenders, 12% were in lapsed attenders, 8% occurred before invitation, and 4% presented in women outside the birth year range for invitation. CONCLUSIONS: Screening has brought about a large increase in detection of early stage cancers. This increase has not yet been fully matched by a corresponding deficit in advanced cancers, possibly because the full effect of screening has not yet been achieved. Reducing the proportion of interval cancers is necessary to increase the effect of screening on mortality.

Aged↗
PubMed1998

Mammographic parenchymal patterns and mode of detection: implications for the breast screening programme.

OBJECTIVES: To assess the effects of mammographic parenchymal patterns on the risk of breast cancer detected at first screen, second screen, and in the interval between these two screens. SETTINGS: A nested case-control study within a screening cohort in East Anglia was designed. The study group comprised 502 patients with cancer at the prevalence screening round, 198 patients with interval cancer, and 175 with cancer at the first incidence screen. These patients were matched with 2601 controls. METHODS: The mammographic parenchymal patterns of breast tissue were assessed according to Wolfe's classification. Statistical analysis was by conditional logistic regression. RESULTS: Overall, 67% of patients and 59% of controls were considered to have high risk pattern (P2 + DY) mammogram. The risk associated with P2 or DY mammographic patterns compared with N1 was higher for interval cancers (odds ratios (ORs) 2.2 and 2.4 respectively) than for screen detected cancers (ORs 1.7 and 1.1 respectively). For interval cancers in the first 18 months after the last negative mammogram, the risk was particularly high (ORs 3.8 for P2 and 4.1 for DY compared with N1). The high risk associated with P2 and DY patterns was concentrated on invasive ductal grade III cancers (ORs 2.7 and 3.8) rather than grade I or II cancers (ORs 1.6 and 1.2). CONCLUSIONS: The study strongly suggests that screening effectiveness is reduced for high risk parenchymal patterns which are associated with high grade cancers. Changes should aim at improving screening sensitivity for dense parenchymal patterns, and the diagnosis of high grade tumours.

Aged↗
PubMed1998

Intracorporal injection of hSlo cDNA in rats produces physiologically relevant alterations in penile function.

The Ca2+-sensitive K+ channel (maxi-K+) is an important modulator of corporal smooth muscle tone. The goal of these studies was twofold: 1) to determine the feasibility of transfecting corporal smooth muscle cells in vivo with the hSlo cDNA, which encodes for the human smooth muscle maxi-K+ channel, and 2) to determine whether transfection of the maxi-K+ channel would affect the physiological response to cavernous nerve stimulation in a rat model in vivo. Intracorporal microinjection of pCMVbeta/Lac Z DNA in 10-wk-old rats resulted in significant incorporation and expression of beta-galactosidase activity in 10 of 12 injected animals for up to 75 days postinjection. Moreover, electrical stimulation of the cavernous nerve revealed that, relative to the responses obtained in age-matched control animals (N = 12), intracavernous injection of naked pcDNA/hSlo DNA was associated with a statistically significant elevation in the mean amplitude of the intracavernous pressure response at all levels of current stimulation (range 0.5-10 mA) at both 1 mo (N = 5) and 2 mo (N = 8) postinjection. Furthermore, qualitatively similar observations were made at 3 mo (N = 2) and 4 mo (N = 2) postinjection. These data indicate that naked hSlo DNA is quite easily incorporated into corporal smooth muscle and, furthermore, that expression is sustained for at least 2 mo in corporal smooth muscle cells in vivo. Finally, after expression, hSlo is capable of measurably altering nerve-stimulated penile erection. Taken together, these data provide compelling evidence for the potential utility of gene therapy in the treatment of erectile dysfunction.

Animals↗
PubMed1997

Retrospective study of reasons for improved survival in patients with breast cancer in east Anglia: earlier diagnosis or better treatment.

OBJECTIVES: To investigate the recent fall in mortality from breast cancer in England and Wales, and to determine the relative contributions of improvements in treatment and earlier detection of tumours. DESIGN: Retrospective study of all women with breast cancer registered by the East Anglian cancer registry and diagnosed between 1982 and 1989. SUBJECTS: 3965 patients diagnosed 1982-5 compared with 4665 patients diagnosed 1986-9, in three age groups 0-49, 50-64, > or = 65 years, with information on stage at diagnosis and survival. MAIN OUTCOME MEASURES: Three year relative survival rates by time period, age group, and stage; relative hazard ratios for each time period and age group derived from Cox's proportional hazards model, adjusted for single year of age and stage. RESULTS: Survival improved in the later time period, although there was little stage specific improvement. The proportion of early stage tumours increased especially in the 50-64 year age group, and adjustment for stage accounted for over half of the improvement in survival in women aged under 65 years. CONCLUSION: Over half of the drop in mortality in women aged under 65 years seems to be attributable to earlier detection of tumours, which has been observed since the mid-1980s. This could have resulted from an increase in breast awareness predating the start of the breast screening programme.

Adolescent↗
PubMed1997

A comparison of the performance and impact of breast cancer screening programmes in East Anglia, U.K. and Bouches du Rhône, France.

The purpose of this study was to compare results from the first screening round of two breast cancer screening programmes of similar design implemented in different health care settings. The East Anglian programme is part of the U.K. National Health Service Breast Screening Programme, which is a centralised programme with a limited number of dedicated screening units. The Bouches du Rhône programme is one of 13 French programmes based on a decentralised model using existing radiology clinics. Compliance and cancer detection rates were lower in the Bouches du Rhône programme. Detection rates for small invasive cancers (< or = 10 mm) were similar in the two programmes, although larger cancers (> or = 20 mm) were detected in the Bouches du Rhône programme. Significantly, the shift towards more favourable distribution of prognostic characteristics associated with screen-detected breast cancers compared with those arising outside the programme is less marked in the Bouches du Rhône programme. This is probably due to the more favourable underlying disease status in the district resulting from a long history of breast awareness and spontaneous mammography.

Breast Neoplasms↗
PubMed1997

Asymptomatic lymphoma associated with elevation of immunoglobulin E.

BACKGROUND: Elevation of immunoglobulin E (IgE) is rarely detected in patients with underlying malignancy. There has been only one report of such a finding in a patient with a T cell lymphoma and none to our knowledge in association with a B-cell lymphoma. OBJECTIVE: To report a patient with elevation of IgE associated with a B-cell lineage lymphoma. MATERIAL AND METHODS: Case report and review of literature. RESULTS: A 73-year-old woman was found to have elevated IgE (11,766 IU/mL) in a routine evaluation for rhinitis. No underlying allergic diathesis or disease associated with IgE elevation was noted. Because of an abnormal lymphocyte profile, an extensive malignancy evaluation was performed which revealed a B-cell lymphoma. CONCLUSION: B-cell lineage lymphoma can be associated with elevated of IgE and should be included in the differential diagnosis in a patient presenting with this finding.

Aged↗
PubMed1997

Traumatic grief as a risk factor for mental and physical morbidity.

OBJECTIVE: The aim of this study was to confirm and extend the authors' previous work indicating that symptoms of traumatic grief are predictors of future physical and mental health outcomes. METHOD: The study group consisted of 150 future widows and widowers interviewed at the time of their spouse's hospital admission and at 6-week and 6-, 13-, and 25- month follow-ups. Traumatic grief was measured with a modified version of the Grief Measurement Scale. Mental and physical health outcomes were assessed by self-report and interviewer evaluation. Survival analysis and linear and logistic regressions were used to determine the risk for adverse mental and physical health outcomes posed by traumatic grief. RESULTS: Survival and regression analyses indicated that the presence of traumatic grief symptoms approximately 6 months after the death of the spouse predicted such negative health outcomes as cancer, heart trouble, high blood pressure, suicidal ideation, and changes in eating habits at 13- or 25-month follow-up. CONCLUSIONS: The results suggest that it may not be the stress of bereavement, per se, that puts individuals at risk for long-term mental and physical health impairments and adverse health behaviors. Rather, it appears that psychiatric sequelae such as traumatic grief are of critical importance in determining which bereaved individuals will be at risk for long-term dysfunction.

Anxiety Disorders↗
PubMed1997

Cathepsin B and middle cerebral artery occlusion in the rat.

Lysosomal proteases, although tightly regulated under physiological conditions, are known to contribute to cell injury after various forms of tissue ischemia have occurred. Because cathepsin B is a prominent lysosomal protease found in brain parenchyma, the authors hypothesized that it may contribute to neuronal cell death after focal cerebral ischemia. The authors measured the expression and spatial distribution of cathepsin B within the ischemic brain in 43 animals by means of immunohistochemical analysis in a rat model of transient middle cerebral artery (MCA) occlusion. Cathepsin B activity was also measured within specific ischemic brain regions by using an in vitro assay (22 animals). In addition, the authors tested the therapeutic effect of preischemic intraventricular administration of stefin A, a cysteine protease inhibitor, on the volume of cerebral infarction after transient MCA occlusion (15 animals). Increased cathepsin B immunoreactivity was detected exclusively within the ischemic neurons after 2 hours of reperfusion following a 2-hour MCA occlusion. Cathepsin B immunolocalization in the ischemic region decreased by 24 hours of reperfusion, but then increased by 48 hours of reperfusion because the infarct was infiltrated by inflammatory cells. Increased immunolocalization of cathepsin B in the inflammatory cells located in the necrotic infarct core continued through 7 days of reperfusion. Cathepsin B enzymatic activity was significantly increased in the ischemic tissue at 2, 8, and 48 hours, but not at 24 hours of reperfusion after 2 hours of MCA occlusion. Continuous intraventricular infusion of stefin A, before 2 hours of MCA occlusion (15 animals), significantly reduced infarct volume compared with control animals (12 animals): the percentage of hemispheric infarct volume was 20+/-3.9 compared with 33+/-3.5 (standard error of the mean; p = 0.025). These data indicate that neuronal cathepsin B undergoes increased expression and activation within 2 hours of reperfusion after a 2-hour MCA occlusion and may be a mechanism contributing to neuronal cell death. Intraventricular infusion of stefin A, an inhibitor of cathepsin B, significantly reduces cerebral infarct volume in rats.

Animals↗
PubMed1997

The effects of prenatal alcohol exposure.

Exposure to alcohol during gestation can cause persistent abnormalities in physical and cognitive development. Children who meet the clinical definition of fetal alcohol syndrome (FAS) are small for their age, exhibit characteristic facial anomalies, and demonstrate deficits in central nervous system development. Alcohol effects in children with prenatal exposure, but not FAS, are similar, although of smaller magnitude and not necessarily present in all three systems. The degree to which a person is affected by prenatal alcohol exposure depends on the amount, timing, and duration of the mother's alcohol consumption during pregnancy as well as maternal characteristics (e.g., age and comorbid psychiatric disorders) and environmental factors (e.g., socioeconomic status and family problems). Some exposure-related effects, such as growth deficits, are directly related to the amount of alcohol consumed, however, so that even a small amount of alcohol may affect child development. Therefore, the best policy continues to be abstinence during pregnancy.

Alcohol Drinking↗