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Biomedical subjects

S Woodward

Publications and source records attributed to S Woodward.

At least 19 recordsLinked to original sources

Fourier transform-infrared spectroscopy as a new method for evaluating host resistance in the Dutch elm disease complex.

Resistance of elms (Ulmus spp.) to the pathogenic fungus Ophiostoma novo-ulmi Brasier depends on chemical and anatomical factors that confine the spread of the pathogen in the vascular system of the host. This study focused on detecting chemical differences in 4-year-old Ulmus minor Mill. seedlings before and after inoculation with a virulent O. novo-ulmi isolate. According to symptom development over 60 days, the trees were divided into resistant (0-33% wilting) and susceptible (67-100% wilting) groups. Histochemical tests and Fourier transform-infrared (FT-IR) spectroscopy analysis were performed on transverse sections of 2-year-old twigs, 2 days before and 40 days after inoculation. Although histochemical tests did not clearly discriminate susceptible from resistant elms, chemical differences between resistant, susceptible and control trees were detected by FT-IR. The average spectrum for resistant tree samples had higher absorbance peaks than the spectra from the susceptible and control samples, indicating increased formation of lignin and suberin. The roles of lignin and suberin in the resistance of the elms against O. novo-ulmi and the usefulness and sensitivity of the FT-IR technique for analyzing metabolic changes caused by pathogens in plants are discussed.

Ascomycota↗

Microglial activation by uptake of fDNA via a scavenger receptor.

The fate of the fragmented DNA (fDNA) observed in neuronal nuclei in Alzheimer brain is unknown. However, its fate is suggested as fDNA is found in the cytoplasm of adjacent activated microglia. After a brief incubation with fDNA, approximately 70% of microglia had fDNA in their cytoplasm, were activated, and overexpressed interleukin-1beta. Microglial activation enhanced uptake whereas blocking scavenger receptors suppressed this uptake. These results suggest that the brain rids itself of fDNA from dying neurons through microglial uptake, activation, and overexpression of IL-1. Such overexpression of IL-1 in Alzheimer brain has been linked to Alzheimer pathogenesis.

Alzheimer Disease↗

Temperamental contributions to the affect family of anxiety.

The discovery of pharmacologic interventions that mute the intensity of anxiety and guilt in some individuals has been a benevolent gift to those who suffer from these disabling states. Although some commentators have wondered about the social consequences of large numbers of asymptomatic persons taking these drugs, few have questioned the advantages for the smaller group of anguished patients. It is likely, however, that, during the next century, scientists will discover a drug that eliminates the feeling components of guilt and remorse while leaving intact the semantic knowledge that certain acts are ethically improper. An individual who took this drug regularly would continue to know that deceiving a friend, lying to a client, and stealing from an employer are morally wrong but would be protected from the uncomfortable feeling of guilt or remorse that accompanies a violation of a personal moral standard. It is reasonable to wonder, therefore, whether our society would be changed in a major way if many citizens were protected from guilt and remorse. Most Western philosophers, especially Kant, made reason the bedrock of conscience. People acted properly, Kant believed, because they knew that the behavior was morally right. All individuals wish to regard the self as virtuous and try to avoid the uncertainty that follows detection of the inconsistency that is created when they behave in ways that are not in accord with their view of the self's desirable attributes. Kant believed that, although the moral emotions restrain asocial acts, they were not necessary for the conduct of a moral life. On the other hand, some philosophers, such as Peirce and Dewey, argued that anticipation of anxiety, shame, and guilt motivate a continued loyalty to one's ethical standards. A person who was certain that he or she was protected from these uncomfortable emotions would find it easier to ignore the moral imperatives acquired during childhood and adolescence. It is not obvious that a drug that blocks remorse also will eliminate the mutual social obligations that make a society habitable; nonetheless, a posture of vigilance that is appropriate for--unlike gorillas--humans can hold representations of envy, anger, and dislike toward people they have never met for a very long time. While we wait for future inquiry to resolve this issue, it is useful to acknowledge that a satisfying analysis of this problem will require a deeper appreciation of the differences between the representations of the biological events that are the foundation of an emotion and the representations that define the semantic networks for the concepts good and bad.

Adult↗

Enantioselective reduction of prochiral ketones by catecholborane catalysed by chiral group 13 complexes

LiGaH4, in combination with the S,O-chelate 2-hydroxy-2'-mercapto-1,1'-binaphthyl (MTBH2), forms an active catalyst for the asymmetric reduction of prochiral ketones, with catecholborane as the hydride source. Enantioface differentiation is on the basis of the steric requirements of the ketone substituents. Aryl/ n-alkyl ketones are reduced in 90-93% ee and RC(O)Me (e.g. R = iPr, cycloC6H11, tBu) in 60-72% ee. Other borane sources and alternative catalyst structures based on indium do not form enantioselective catalysts.

Journal Article↗

Overexpression of the neuritotrophic cytokine S100beta precedes the appearance of neuritic beta-amyloid plaques in APPV717F mice.

Homozygous APPV717F transgenic mice overexpress a human beta-amyloid precursor protein (betaAPP) minigene encoding a familial Alzheimer's disease mutation. These mice develop Alzheimer-type neuritic beta-amyloid plaques surrounded by astrocytes. S100beta is an astrocyte-derived cytokine that promotes neurite growth and promotes excessive expression of betaAPP. S100beta overexpression in Alzheimer's disease correlates with the proliferation of betaAPP-immunoreactive neurites in beta-amyloid plaques. We found age-related increases in tissue levels of both betaAPP and S100beta mRNA in transgenic mice. Neuronal betaAPP overexpression was found in cell somas in young mice, whereas older mice showed betaAPP overexpression in dystrophic neurites in plaques. These age-related changes were accompanied by progressive increases in S100beta expression, as determined by S100beta load (percent immunoreactive area). These increases were evident as early as 1 and 2 months of age, months before the appearance of beta-amyloid deposits in these mice. Such precocious astrocyte activation and S100beta overexpression are similar to our earlier findings in Down's syndrome. Accelerated age-related overexpression of S100beta may interact with age-associated overexpression of mutant betaAPP in transgenic mice to promote development of Alzheimer-like neuropathological changes.

Aging↗

Community perceptions about the tobacco industry and tobacco control funding.

OBJECTIVES: To determine community views about the believability and standards of honesty and ethics of tobacco companies, related policy options, and mechanisms for tobacco control funding. METHOD: A representative population survey of 808 South Australians aged 18 years and older, contacted by telephone, using an electronic white pages sampling frame, with a response rate of 72%. RESULTS: 80% of respondents and 74% of smokers thought tobacco companies mostly did not or never told the truth about smoking and health, children and smoking and addictiveness of tobacco. With regard to perceived standards of honesty and ethics, tobacco company executives were rated the lowest of all professional groups, with 74% of respondents judging them to have low or very low standards. 89% of smokers would support full product information on the pack about chemicals and additives in cigarettes. 77% thought shopkeepers should pay back the amount they gain from children smoking cigarettes and 80% thought tobacco companies should do so, or be fined or taxed accordingly. 53% agreed the government should spend an amount equal to the amount gained from children's smoking and 21% indicated a higher expenditure. CONCLUSION: Tobacco companies are held in low regard by the public and by smokers who are their customers. There is a high degree of support for tobacco control efforts to be financed by being indexed to the level of children's smoking in the community, through the amount made by shopkeepers, manufacturers and the government from children's cigarette consumption.

Adult↗

The impact of smoke-free workplaces on declining cigarette consumption in Australia and the United States.

OBJECTIVES: This study estimates the contribution of smoke-free workplaces to the recent national declines in cigarette consumption in Australia and the United States. METHODS: Nineteen studies of the impact of smoke-free workplaces on workday cigarette consumption were reviewed. The number and cost of cigarettes forgone were calculated and extrapolated to a scenario in which all indoor work areas were smoke-free. RESULTS: Of the 19 studies, 18 reported declines in daily smoking rates, and 17 reported declines in smoking prevalence. Smoke-free workplaces are currently responsible for an annual reduction of some 602 million cigarettes, or 1.8% of all cigarettes that might otherwise be consumed, in Australia, and an annual reduction of 9.7 billion cigarettes (2%) in the United States. Approximately 22.3% of the 2.7 billion decrease in cigarette consumption in Australia between 1988 and 1995 can be attributed to smoke-free workplaces, as can 12.7% of the 76.5 billion decrease in the United States between 1988 and 1994. CONCLUSIONS: If workplaces were universally smoke-free, the number of cigarettes forgone annually would increase to 1.14 billion (3.4%) in Australia and 20.9 billion (4.1%) in the United States.

Australia↗

Expression of the Zn finger gene, EVI-1, in acute promyelocytic leukemia.

The EVI-1 gene encodes a Zn finger, DNA binding protein previously detected in some acute myelogenous leukemias (AML) and myelodysplasias (MDS), but not in normal marrow or cord blood cells. Experimental studies suggest EVI-1 blocks cellular differentiation by binding to GATA-1 or other specific DNA sequences controlling gene expression, and may be involved in the pathogenesis of some AMLs. To further define potential roles for EVI-1 in leukemia pathogenesis, we studied its regulation in acute promyelocytic leukemias (APL). Seven of 11 APL cases expressed EVI-1 RNA detected by RNA PCR at diagnosis, and expression was detected in two additional cases after treatment with all-trans retinoic acid (ATRA). Two of four cases studied at relapse also expressed EVI-1 RNA. To investigate regulation of EVI-1 expression in APL, we examined its expression in the NB4 APL cell line. NB4 cells did not express EVI-1 under basal conditions, but expressed EVI-1 after ATRA-induced differentiation. When NB4 cells were exposed to ATRA and transferred to cultures with N,N'-hexamethylene-bis-acetamide (HMBA), differentiation occurred but EVI-1 RNA was not detected, indicating that EVI-1 expression was not required for terminal, NB4 differentiation. ATRA-resistant NB4 cells were obtained by continuous culture in gradually increasing concentrations of ATRA. These cells did not express markers of differentiation but continued to express EVI-1 for several weeks even after ATRA withdrawal. To assess whether expression of the APL PML-RAR alpha fusion gene alone was sufficient for ATRA induction of EVI-1, the PML-RAR alpha gene cDNA was expressed in U937 histiocytic lymphoma cells. ATRA treatment of PML-RAR alpha-transfected or control U937 cells did not induce EVI-1 expression. In conclusion, this study demonstrates the EVI-1 gene is consistently expressed in APL cells either constitutively or after ATRA treatment. ATRA represents the first biologically active agent shown to specifically regulate EVI-1 expression in blood cells. In contrast to previous studies in AML and MDS, the pattern of EVI-1 expression suggests it may facilitate rather than inhibit myeloid differentiation during ATRA treatment. However, effects of EVI-1 expression are likely to be complex, and expression in ATRA-resistant APL cells may indicate multiple roles for this gene.

Acetamides↗

Expression of the zinc finger gene EVI-1 in ovarian and other cancers.

The EVI-1 gene was originally detected as an ectopic viral insertion site and encodes a nuclear zinc finger DNA-binding protein. Previous studies showed restricted EVI-1 RNA or protein expression during ontogeny; in a kidney and an endometrial carcinoma cell line; and in normal murine oocytes and kidney cells. EVI-1 expression was also detected in a subset of acute myeloid leukaemias (AMLs) and myelodysplasia. Because EVI-1 is expressed in the urogenital tract during development, we examined ovarian cancers and normal ovaries for EVI-1 RNA expression using reverse transcription polymerase chain reaction (RT-PCR) and RNAase protection. Chromosome abnormalities were examined using karyotypes and whole chromosome 3 and 3q26 fluorescence in situ hybridisation (FISH). RNA from six primary ovarian tumours, five normal ovaries and 47 tumour cell lines (25 ovarian, seven melanoma, three prostate, seven breast and one each of bladder, endometrial, lung, epidermoid and histiocytic lymphoma) was studied. Five of six primary ovarian tumours, three of five normal ovaries and 22 of 25 ovarian cell lines expressed EVI-1 RNA. A variety of other non-haematological cancers also expressed EVI-1 RNA. Immunostaining of ovarian cancer cell lines revealed nuclear EVI-1 protein. In contrast, normal ovary stained primarily within oocytes and faintly in stroma. Primary ovarian tumours showed nuclear and intense, diffuse cytoplasmic staining. Quantitation of EVI-1 RNA, performed using RNAase protection, showed ovarian carcinoma cells expressed 0 to 40 times the EVI-1 RNA in normal ovary, and 0-6 times the levels in leukaemia cell lines. Southern analyses of ovarian carcinoma cell lines showed no amplification or rearrangements involving EVI-1. In some acute leukaemias, activation of EVI-1 transcription is associated with translocations involving 3q26, the site of the EVI-1 gene. Ovarian carcinoma karyotypes showed one line with quadruplication 3(q24q27), but no other clonal structural rearrangements involving 3q26. However, whole chromsome 3 and 3q26 FISH performed on lines with high EVI-1 expression showed translocations involving chromosome 3q26. EVI-1 is overexpressed in ovarian cancer compared with normal ovaries, suggesting a role for EVI-1 in solid tumour carcinogenesis or progression. Mechanisms underlying EVI-1 overexpression remain unclear, but may include rearrangements involving chromosome 3q26.

Blotting, Southern↗

Nutritional support for head-injured patients.

Brain-injured patients require increased nutritional support in order to prevent complications of inadequate nutrition. Nurses are in a strong position to influence the nutritional support provided to such patients.

Craniocerebral Trauma↗

Core body temperature during menopausal hot flushes.

OBJECTIVE: To measure core body temperature by ingested radiotelemetry pill and rectal temperature during menopausal hot flushes under controlled laboratory conditions. DESIGN: Patients were recorded during sleep using both methods in a sound-proofed, temperature and humidity-controlled laboratory room. SETTING: University medical center. PATIENTS: Eight postmenopausal women who were amenorrheic for > or = 1 year and reported frequent hot flushes. RESULTS: Thirty-seven hot flushes were detected by criterion increases in sternal skin conductance level. Significant increases in telemetered but not rectal temperature occurred before 24 of the hot flushes. CONCLUSIONS: Core body temperature elevations precede a majority of menopausal hot flushes and serve as one trigger of this heat-loss phenomenon.

Body Temperature↗

Core body temperature and circadian rhythm of hot flashes in menopausal women.

Postmenopausal hot flashes are characterized by sweating and peripheral vasodilation and occur more frequently during increased heat loads. The circadian rhythm of core body temperature (TC) is well known and suggests that hot flashes will be most frequent when core temperature is highest. This hypothesis has not been tested previously. Ten symptomatic and six asymptomatic postmenopausal women were recruited from advertisements and screened. Each received 24-h ambulatory monitoring of sternal skin conductance levels to detect hot flashes, ambient temperature, skin temperature, and TC. The last measure was recorded using an ingested radiotelemetry pill. Cosinor analysis demonstrated a circadian rhythm (P < 0.02) of hot flashes with a peak at about 1825 h. TC values of the symptomatic women were lower than those of the asymptomatic women (P < .05) from 0000-0400 h and at 1500 and 2200 h. The majority of hot flashes were preceded by elevations in TC. Thus, elevated TC may serve as one trigger of menopausal hot flashes.

Body Temperature↗

Nurse and patient perceptions of pain.

Patient pain is a problem frequently encountered by nurses, who are often directly responsible for its management. Accurate pain assessment is vital for appropriate management. The nurse's role in pain control should evolve to one of empowering patients to determine the management of their own pain where possible.

Attitude of Health Personnel↗

Expression of EVI1 in myelodysplastic syndromes and other hematologic malignancies without 3q26 translocations.

The EVI1 gene encodes a zinc-finger, DNA-binding protein originally described as the transforming gene associated with a common ecotropic viral insertion site in myeloid leukemias. Previous studies demonstrated EVI1 expression in human leukemias in cases with 3q26 translocations, but not in normal blood or bone marrow. These studies also suggested an association between EVI1 expression and chromosome 7 deletion (del). Because of this association, we examined expression of EVI1 using RNA polymerase chain reaction (PCR) in patients with myelodysplastic syndromes (MDS) and acute leukemia with and without 3q26 translocations. EVI1 RNA was expressed in 29% of 34 (95% confidence interval, 20% to 50%) patients with the MDS subtypes refractory anemia (RA), refractory anemia with excess blasts (RAEB), or refractory anemia with excess blasts in transformation (RAEB-T). The vast majority of these cases occurred in patients with RAEB and RAEB-T. EVI1 expression was not detected in patients with chronic myelomonocytic leukemia (CMML), normal bone marrow or cord blood, or a variety of other hematologic malignancies. EVI1 RNA was detected in three of 18 patients with acute myelogenous leukemia (AML) and in two of four patients with acute promyelocytic leukemia (APL). Karyotypes showed that only one AML patient had karyotype 3q26 abnormalities, indicating that EVI1 expression is associated with cases that do not have structural abnormalities involving chromosome 3q26. These studies document for the first time the abnormal expression of EVI1 RNA by patients with MDS, and suggest an important role for EVI1 in the pathogenesis or progression of some myeloid malignancies.

Adult↗