Momentum for strong workplace advocacy structure within ANA continues.
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American Nurses' Association↗
Biomedical subjects
A Green
Publications and source records attributed to A Green.
Heterodimerization is required for the formation of a functional GABA(B) receptor.
GABA (gamma-aminobutyric acid) is the main inhibitory neurotransmitter in the mammalian central nervous system, where it exerts its effects through ionotropic (GABA(A/C)) receptors to produce fast synaptic inhibition and metabotropic (GABA(B)) receptors to produce slow, prolonged inhibitory signals. The gene encoding a GABA(B) receptor (GABA(B)R1) has been cloned; however, when expressed in mammalian cells this receptor is retained as an immature glycoprotein on intracellular membranes and exhibits low affinity for agonists compared with the endogenous receptor on brain membranes. Here we report the cloning of a complementary DNA encoding a new subtype of the GABAB receptor (GABA(B)R2), which we identified by mining expressed-sequence-tag databases. Yeast two-hybrid screening showed that this new GABA(B)R2-receptor subtype forms heterodimers with GABA(B)R1 through an interaction at their intracellular carboxy-terminal tails. Upon expression with GABA(B)R2 in HEK293T cells, GABA(B)R1 is terminally glycosylated and expressed at the cell surface. Co-expression of the two receptors produces a fully functional GABA(B) receptor at the cell surface; this receptor binds GABA with a high affinity equivalent to that of the endogenous brain receptor. These results indicate that, in vivo, functional brain GABA(B) receptors may be heterodimers composed of GABA(B)R1 and GABA(B)R2.
Amino Acid Sequence↗
Relationship between number of ovulatory cycles and accumulation of mutant p53 in epithelial ovarian cancer.
BACKGROUND: It has been suggested that increased numbers of ovulations might increase the risk of p53 gene (also known as TP53) mutation in the ovarian epithelium, thereby leading to the development of cancer. The data supporting this hypothesis have come from an observation that accumulation of p53 protein in epithelial ovarian cancer was strongly associated with increasing numbers of ovulatory cycles. We have further investigated the association between ovulatory history and p53 gene mutation by use of data from a large case-control study of ovarian cancer in Australia. METHODS: Tissue blocks were available for immunohistochemical analysis of p53 protein from 234 case subjects, aged 18-79 years, who had invasive epithelial ovarian cancer. Epidemiologic data were also available for these women and for 855 control subjects. Case-case comparisons were made by use of prevalence ratios and 95% confidence intervals (CIs), and case-control comparisons were made by use of odds ratios (ORs) and 95% CIs. All statistical tests were two-sided. RESULTS: There was no association between p53 accumulation and years of ovulation. Women with p53-positive cancers had undergone an average of 29.3 years of ovulation compared with 29.0 years of ovulation for women with p53-negative cancers (P=.8). Although the overall risk of ovarian cancer development was significantly increased in women who had undergone more years of ovulation (OR=2.17; 95% CI =1.54-3.05-for > or =35 years versus <23 years of ovulation), there was no difference in the risk associated with p53-positive and p53-negative cancers. CONCLUSIONS: These results confirm the association between increased ovulation and ovarian cancer risk but do not support the hypothesis that this association is due to an increased risk of p53 mutation with a greater number of ovulatory cycles.
Adult↗
Alteration of zif268 zinc-finger motifs gives rise to non-native zinc-co-ordination sites but preserves wild-type DNA recognition.
Zinc fingers are among the major structural motifs found in proteins that are involved in eukaryotic gene regulation. Many of these zinc-finger domains are involved in DNA binding. This study investigated whether the zinc-co-ordinating (Cys)2(His)2 motif found in the three zinc fingers of zif268 could be replaced by a (Cys)4 motif while still preserving DNA recognition. (Cys)2(His)2-to-(Cys)4 mutations were generated in each of the three zinc fingers of zif268 individually, as well as in fingers 1 and 3, and fingers 2 and 3 together. Whereas finger 1 and finger 3 tolerate the switch, such an alteration in finger 2 renders the polypeptide incapable of DNA recognition. The protein-DNA interaction was examined in greater detail by using a methylation-interference assay. The mutant polypeptides containing the (Cys)4 motif in fingers 1 or 3 recognize DNA in a manner identical to the wild-type protein, suggesting that the (Cys)4 motif appears to give rise to a properly folded finger. Additional results indicate that a zif268 variant containing a (Cys)2(His)(Ala) arrangement in finger 1 is also capable of DNA recognition in a manner identical to the wild-type polypeptide. This appears to be the first time that such alterations, in the context of an intact DNA-binding domain, have still allowed for specific DNA recognition. Taken together, the work presented here enhances our understanding of the relationship between metal ligation and DNA-binding by zinc fingers.
Amino Acid Sequence↗
Identification of non-heme diiron proteins that catalyze triple bond and epoxy group formation.
Acetylenic bonds are present in more than 600 naturally occurring compounds. Plant enzymes that catalyze the formation of the Delta12 acetylenic bond in 9-octadecen-12-ynoic acid and the Delta12 epoxy group in 12,13-epoxy-9-octadecenoic acid were characterized, and two genes, similar in sequence, were cloned. When these complementary DNAs were expressed in Arabidopsis thaliana, the content of acetylenic or epoxidated fatty acids in the seeds increased from 0 to 25 or 15 percent, respectively. Both enzymes have characteristics similar to the membrane proteins containing non-heme iron that have histidine-rich motifs.
Acetylene↗
The shady side of solar protection.
OBJECTIVE: To determine the value of shade in protecting humans from solar ultraviolet (UV) radiation. DESIGN AND SETTING: Measurement with photometers of protection factors for ultraviolet B radiation (UVB) and for total solar radiation for different types of trees and other structures during the summer months (1995-1997) in south-east Queensland. (The protection ratio is the ratio of the intensity of UVB or total solar radiation in direct sunlight to that in shade.) RESULTS: For summer sun at midday, the mean (SD) UV protection ratio for the shade of trees (n = 65) was 4.21 (1.36) on a horizontal surface and 1.33 (0.30) on a vertical surface. In contrast, the mean (SD) protection ratio for total solar energy (primarily infrared) was much higher (12.1 [1.4]). Trees common in recreational areas in Australia (eucalypts: UV protection ratio, 3.52 [0.79]; Norfolk Island pines: UV protection ratio, 3.72 [0.98]) offered reduced protection compared with trees with more dense foliage (UV protection ratio, 5.48 [1.44]). Over a whole day, measurement of shade by trees and other structures showed that the UV protection ratio was lower in the morning and afternoon. Shade from awnings, buildings and hats gave similar results to those for trees. Both at midday and over a whole day satisfactory protection (UV protection ratio > 15) was obtained only in shade which eliminated exposure to the sky as well as to direct sunlight; for example, in thickly wooded areas and under low, widely overhanging structures. CONCLUSIONS: Most forms of shade, while useful, offer people insufficient protection from solar UV. A fair-skinned person sheltering under a tree could suffer sunburn after less than one hour. There is a need for appropriate design of structural shade, use of other solar protection measures in conjunction with shade, and research on behavioural responses to shade.
Facility Design and Construction↗
[Insulin-dependent diabetes in the county of Funen 1970-2020. An epidemiological description].
We present an epidemiological model applicable to insulin-dependent diabetes mellitus (IDDM), based on which prevalence rates are estimated from assumed rates of incidence and mortality of diabetes. The model is illustrated by analysing epidemiological data on IDDM in Fyn County, Denmark for the period 1970-1990, with predictions of prevalence rates during 1990-2020. The epidemiological model assumes known prevalence rates as well as incidence rates and mortality at a given point of time. Under assumed rates of incidence and mortality of IDDM and its complications, the prevalence rate is the dependent variable which is estimated as a function of calendar time. We used epidemiological data on IDDM (operationally defined as insulin-treated diabetes with onset before age 30 years), blindness and nephropathy as well as mortality as reported for the years 1973 and 1987 in Fyn County, Denmark. During 1970-1990 the prevalence of IDDM increased steadily, due to increasing incidence and decreasing risk of complications and mortality. The relative prevalence of patients with nephropathy increased whereas that of blind patients decreased considerably. Under specified assumptions regarding the future levels of incidence of disease, complications and of mortality, it is estimated that the prevalence rate of IDDM in the year 2020 will be 45-60% higher than the level in 1990. The relative prevalence of patients with nephropathy will increase further, whereas the relative prevalence of blind patients will remain constant at a low level. We conclude that IDDM will represent an increasing public health problem in Denmark over the next decades, with increasing overall prevalence rates and a rising proportion of patients with nephropathy. The major determinants of this trend are increasing incidence, combined with declining mortality and declining risk of complications. It is recommended that epidemiological modelling techniques be further developed to provide improved data for the planning of the future diabetes care.
Denmark↗
The origin of red blood cell biopterin.
Data are presented to support the hypothesis that the biopterin content of red blood cells arises during erythropoiesis. Only when the plasma concentration rises above the erythrocyte concentration of biopterin is there likely to be diffusion into the cell.
Adult↗
Epidemiology of childhood IDDM in Athens: trends in incidence for the years 1989-1995. Eurodiab ACE G1 Group.
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Adolescent↗
Alterations in colonic mucosal vessels in patients with cirrhosis and noncirrhotic portal hypertension.
Changes in intestinal mucosal microvasculature as a cause of lower gastrointestinal hemorrhage in patients with portal hypertension have been well documented clinically, but the analogous histomorphological changes have not been well characterized. The goal of this study was to evaluate qualitative and quantitative changes in colonic mucosal vessels in patients with cirrhosis or clinically evident portal hypertension and to correlate these changes with endoscopic and clinical findings. Colon biopsy or resection specimen slides from 46 patients with biopsy-proven cirrhosis (44 patients) or noncirrhotic portal hypertension (two patients) were reviewed. Immunoperoxidase stain for CD34 antigen was used to facilitate visualization of mucosal vessels, and vessel diameter was measured with a micrometer. Patients with inflammatory bowel disease were excluded. Twenty-four normal colon biopsy specimens served as controls. Mucosal vessels were divided into superficial, intermediate, and deep layers. As a group, the cirrhotic patients had a significantly higher mean diameter of vessels in all three layers. Qualitatively, increased numbers of small vessels and prominent branching were noted, especially in the superficial and intermediate layers. Tortuous, thick-walled vessels, suggesting arterialization of venules, were present in some cases. Eleven patients had endoscopic findings suggestive of vascular abnormalities, including erythematous mucosal patches, red macules, and telangiectasias. Eighteen had esophageal varices, and five had portal gastropathy. Nineteen patients had gastrointestinal (GI) bleeding, localized to the lower GI tract in 11. These qualitative and quantitative findings suggest that colonic mucosal vascular lesions are common in portal hypertension and may represent a potential source of clinically significant lower GI hemorrhage in these patients.
Adult↗
Comparative pupil dilation using phenylephrine alone or in combination with tropicamide.
OBJECTIVE: A prevalence survey of actinic and other eye diseases was conducted in Nambour, Queensland, Australia, in 1992. Pupils were dilated with phenylephrine alone for cataract identification because there were concerns that patient discomfort, due to cycloplegia occurring with the usual dilating agents of tropicamide and phenylephrine, may influence future compliance in an associated intervention study. This validation study was undertaken to measure the possible underestimation of cataract prevalence in this community study, which may have occurred because of inadequate dilation from phenylephrine alone. DESIGN: The study design was a repeated measures experimental design. PARTICIPANTS: Forty-seven normal subjects participated in the study. Both eyes were tested. INTERVENTION: Pupil diameter after dilation with three drops of 10% phenylephrine alone was compared with pupil diameter after dilation with three drops of 10% phenylephrine together with three drops of 1% tropicamide. The two regimens were given to the same subjects 1 week apart. Reversal was attempted with thymoxamine hydrochloride 0.5%. MAIN OUTCOME MEASURES: Pupil diameter was assessed using a Neitz cataract camera, and accommodation reserve also was measured. Subjects' subjective appreciation of return of ocular function was assessed by a questionnaire. Repeated measures analysis of variance, paired t test, McNemar's test, and Wilcoxon signed rank test were used to analyze outcomes. RESULTS: Mean maximum pupil size with 10% phenylephrine and 1% tropicamide was significantly larger than pupil size after the use of 10% phenylephrine alone (F1,19 = 18.99, P = 0.0003). However, there was no significant difference between the two dilation regimens when comparing the proportion of subjects who dilated to 6 mm or more (McNemar's X(2)1 = 2.7, P > 0.1). Compared with 10% phenylephrine and 1% tropicamide, pupil diameters were significantly smaller (t46 = 16.77, P = 0.0001), and accommodation reserve greater (t46 = 4.14, P = 0.0001), 40 minutes after reversal with thymoxamine in the group dilated with 10% phenylephrine alone. CONCLUSION: Pupil dilation with 10% phenylephrine alone, if allowed at least 40 minutes to act, will be as satisfactory for the identification of cataracts in a normal population as 10% phenylephrine and 1% tropicamide and is more acceptable because of reduced problems with glare and accommodation.
Accommodation, Ocular↗
Relationship of endogenous sex hormones to lipids and blood pressure in mid-aged women.
PURPOSE: The relationship between endogenous sex hormones and blood lipids was examined in a representative sample of 438 Australian-born women 45 to 56 years of age taking part in a longitudinal study of the menopausal transition. Data from 363 women who were taking neither exogenous hormones nor lipid-altering medications, were not diabetic, and who had provided blood samples were available for analysis. METHODS: Multiple linear regression was used to examine the relationship between sex hormones and high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), triglycerides, and diastolic blood pressure (DBP), taking account of the effects of age, body mass index (BMI), smoking, alcohol intake, and exercise. RESULTS: There was no significant relationship between estradiol and HDL, LDL, triglyceride, or DBP levels. Free androgen index was positively associated with LDL. However, BMI was an important predictor of all three lipid measures and DBP. HDL was positively associated with age and was highest among women with lowest BMI, high alcohol intake, and in nonsmokers. LDL increased with BMI, free androgen index, and age, but was lower amongst women who exercised more than two or three times per week. Triglyceride also increased with BMI, and was higher among smokers. DBP increased with BMI only. CONCLUSIONS: The results do not support the view that endogenous sex hormones are strongly associated with cardiovascular risk factors around the time of menopause.
Androgens↗
Milk consumption, galactose metabolism and ovarian cancer (Australia).
OBJECTIVES: It has been suggested that increased exposure to galactose, due to high consumption of dairy foods or reduced galactose metabolism, is associated with the development of ovarian cancer. We have investigated this in a large case-control study conducted in three Australian states between 1990 and 1993. METHODS: Approximately 800 histologically-confirmed cases, 800 community controls and 300 controls recruited through breast-screening clinics completed dietary questionnaires. Approximately 100 cases and all breast-screening controls also provided a blood sample for analysis of galactose-1-phosphate-uridyltransferase (GALT). RESULTS: Ovarian cancer risk was positively associated with increasing consumption of whole milk and other full-fat dairy foods, but was not associated with consumption of low-fat dairy foods and was inversely related to consumption of skimmed milk. There was no association between ovarian cancer and GALT except among women with abnormally low GALT who had a non-significant 2.5-fold increased risk of ovarian cancer. CONCLUSIONS: These data do not support the hypothesis that galactose plays a major role in the development of ovarian cancer and suggest that reported associations between milk consumption and ovarian cancer are due to the fat content of milk and not to lactose or galactose. An increased risk of ovarian cancer in women with abnormally low levels of GALT cannot, however, be ruled out.
Adolescent↗
Suppression of tumorigenic and metastatic potentials of human melanoma cell lines by mutated (143 Val-Ala) p53.
Metastatic melanoma, compared with other cancers, appears to be unusual because of its low frequency of p53 mutations and prevalence of wild-type p53 protein in advanced malignancy. Here, we examined the effects of wild-type and mutated p53 (143 Val-Ala) on tumorigenic and metastatic potential of two human melanoma cell lines. The cell line UISO-MEL-4 contains wild-type p53 and is tumorigenic, whereas UISO-MEL-6 lacks p53 and produces lung and liver metastasis upon s.c. injection into athymic mice. Our study showed that UISO-MEL-4 stably transfected with wild-type p53 cDNA driven by cytomegalovirus promoter-enhancer sequences expressed high levels of p53 and p21 and formed s.c. tumours in vivo. Mutated p53 (143 Val-Ala) expression, on the other hand, inhibited tumour growth in 50% of cases and produced significantly slower growing non-metastatic tumours. Reduced tumour growth involved necrotic as well as apoptotic cell death. Inhibition of tumour growth was abrogated by the addition of Matrigel (15 mg ml(-1)). With UISO-MEL-6 cells, stably transfected with mutant p53, tumour growth was delayed and metastasis was inhibited. In soft agar colony formation assay, both wild-type and mutant p53 transfectants reduced anchorage-independent colony formation in vitro. These data suggest that mutated (143 Val-Ala) p53, which retains DNA binding and some of the transactivation functions of the wild-type p53 protein, suppresses tumorigenic and metastatic potentials of human melanoma cell lines in vivo.
Animals↗
Serum inhibins A and B fall differentially as FSH rises in perimenopausal women.
BACKGROUND: Serum FSH levels rise with increasing age in normal women, particularly as they enter the menopausal transition and progress to the postmenopausal state. The contributions of decreasing levels of inhibin-A (INH-A) and inhibin-B (INH-B) to this rise are presently unclear, as there are no reports of dimeric INH levels in relation to menopausal status. The present study was undertaken in order to provide preliminary data on relationships amongst the dimeric inhibins, oestradiol (E2) and FSH in normal subjects of defined menopausal status. METHODS: Single serum samples were obtained between cycle days 3 and 8 in regularly cycling women, or at random in those with irregular cycles or amenorrhoea, in 110 women, aged 48-59 years, in the third year of a prospective longitudinal study of the menopausal transition, 'The Melbourne Women's Mid-Life Health Project'. Samples were assayed for FSH, E2, INH-A, INH-B and immunoreactive inhibin (IR-INH) and results were analysed following logarithmic transformation. Undetectable values were assigned the limit of sensitivity of the respective assays. The relationships between hormones were evaluated as a function of menopausal stage. The latter was assigned as Stage 1, premenopausal (no reported change in menstrual cycle pattern), Stage 2, early peri-menopausal (reported change in menstrual cycle frequency in the preceding year with a bleed in the preceding 3 months), Stage 3, late peri-menopausal (no menses in the preceding 3-11 months) and Stage 4, postmenopausal (no menses in the preceding 12 months). RESULTS: The hormone concentrations in premenopausal subjects (geometric means, FSH 13.5 IU/l, E2 306 pmol/l, IR-INH 217 U/l, INH-A 96 ng/l, and INH-B 48 ng/l) were used as reference points for the other stages of menopausal status. Early peri-menopausal subjects had significantly lower levels of IR-INH (147 U/l) and INH-B (13.5 ng/l) in the presence of a small, statistically nonsignificant rise in FSH (to 21.4 U/l) and no significant change in E2 or INH-A. In late peri-menopausal subjects, IR-INH fell to 76 U/l, INH-A fell to 4.2 ng/l, whilst INH-B was not significantly different at 14 ng/l. FSH had risen significantly to 72.21 U/l. Oestradiol also fell significantly to 89 pmol/l. In the postmenopausal subjects there were no further significant changes in the peptide hormones or FSH, but E2 fell further to 41 pmol/l. There was a significant (P < 0.05) inverse correlation between FSH and E2 (R = -0.78), FSH and IR-INH (R = -0.66), FSH and INH-A (R = -0.53), FSH and INH-B (R = -0.29) while IR-INH and either INH-A or INH-B were positively correlated (R = +0.57 and +0.35, respectively). The data are consistent with negative feedback roles for both dimeric inhibins and E2 as contributors to the regulation of FSH secretion as menopausal status changes. CONCLUSIONS: The major significant endocrine event in women in the early peri-menopausal phase of the menopausal transition is a substantial fall in the circulating levels of inhibin-B with no significant change in inhibin-A or oestradiol. Progression to late peri-menopausal status is accompanied by a marked fall in inhibin-A and oestradiol and a rise in FSH without further change in inhibin-B. Inhibin-B, a marker of follicle number, is a significant factor in the endocrinology of the menopausal transition.
Cross-Sectional Studies↗
Functional characterization and exon 2-intron 2-exon 3 gene sequence of HLA-B*2712 as found in a British family.
The HLA-B*27 group of alleles has been extensively studied due to the association of particular B*27 alleles with ankylosing spondylitis (AS). We describe here an HLA-B*27 allele (B*2712) encoding an antigen that lacks reactivity with B27 monoclonal antibodies (moabs) and alloantisera but reacts with some B40/B60 moabs and alloantisera and expresses the Bw6 public epitope. This allele was discovered by the segregation of an HLA-B allele undetectable by PCR-SSP within a Caucasian family from the British population referred for routine bone marrow transplant HLA typing and found in the haplotype A*29; B*2712; Cw*1203; DRB1*13; DQB1*0603. Serological typing showed a lack of reactivity with four B27 moabs and four alloantisera but positive reactivity with moabs and alloantisera specific for B40/B60 and Bw6 public epitopes. Subsequent sequencing showed the closest homology was with B*2708 with three mismatches in exon 2 at positions 204, 209 and 210. The intron 2 sequence was identical with other B*27 lineage alleles including a 2 base pair deletion at positions 95 and 96. The relationship between HLA-B*2712 and reported B60 associations with susceptibility to AS remains to be determined.
Alleles↗
Systemic lupus erythematosus in Denmark: clinical and epidemiological characterization of a county-based cohort.
A population based cohort of patients with systemic lupus erythematosus (SLE) was recruited from a for epidemiological purposes representative Danish region. Patients were ascertained from 4 different sources with a high degree of completeness as estimated by using capture-recapture analysis. The diagnosis was verified by means of case records, patient interviews, and clinical examinations. Patients were classified according to the 1982 revised ACR criteria as Definite SLE (D-SLE) fulfilling > or = 4 criteria and Incomplete SLE (I-SLE) with < 4 criteria. As of January 1, 1995, the point prevalences of D-SLE and I-SLE were 21.7 and 5.2 per 100000 respectively. The cohort comprised 98% white Europeans. The annual incidence of D-SLE increased from 1.0/100,000 to 3.6/100,000 during the study period 1980-94. D-SLE patients had clinical profiles comparable to other Western European study populations. The I-SLE subclass had milder disease manifested by lower criterial load and absence of cerebral and kidney involvement. Tissue and organ damage expressed as SLICC-score increased in the order of live I-SLE, live D-SLE, and deceased patients.
Adolescent↗
Hematopoietic cytokine-mediated FDG uptake simulates the appearance of diffuse metastatic disease on whole-body PET imaging.
FDG-PET is increasingly being used to assess malignant tumors. However, leukocyte colony-stimulating factors (CSFs), which promote the expansion of hematopoietic bone marrow, have also been demonstrated to cause increased bone-marrow FDG uptake. Three hundred FDG-PET studies conducted over a 1-year period were reviewed for diffuse bone-marrow uptake. Elevated bone-marrow uptake on PET was correlated with pathological findings and courses of granulocyte-CSF (G-CSF) therapy. These results demonstrate that G-CSF mediated FDG uptake in bone marrow is often indistinguishable from that caused by disseminated metastatic disease. However, the bone-marrow response to G-CSF decreases rapidly following the last CSF administration. Therefore, FDG-PET in patients receiving G-CSF should be delayed, when possible, until 5 days after the end of G-CSF therapy.
Adolescent↗