ABSTRACT
We evaluated the effects of fatty acid (FA) supplement blends containing 60% palmitic acid (C16:0) and either 30% stearic acid (C18:0) or 30% oleic acid (cis-9 C18:1) on nutrient digestibility and milk production of low- and high-producing dairy cows. Twenty-four multiparous Holstein cows [118 ± 44 d in milk (DIM)] were divided into 2 blocks by milk production and then randomly assigned to treatment sequence in four 3 × 3 Latin squares within production level, balanced for carryover effects in three consecutive 21-d periods. Cows were blocked by milk yield and assigned to 1 of 2 groups (n = 12 per group): (a) low group (42.5 ± 3.54 kg/d; 147 ± 42 DIM) and (b) high group (55.8 ± 3.04 kg/d; 101 ± 34 DIM). Commercially available fat supplements were combined to provide treatments that consisted of the following: (1) control (CON; diet with no supplemental FA), (2) FA supplement blend containing 60% C16:0 and 30% C18:0 (PA+SA), and (3) FA supplement blend containing 60% C16:0 and 30% cis-9 C18:1 (PA+OA) The FA blends were fed at 1.5% of dry matter (DM) and replaced soyhulls from CON. Preplanned contrasts were (1) overall effect of FA treatments [CON vs. the average of the FA treatments (FAT); 1/2 (PA+SA + PA+OA)], and (2) effect of FA supplement (PA+SA vs. PA+OA). Regardless of production level, overall FAT reduced DMI compared with CON. Also, regardless of level of milk production, PA+OA increased total-tract FA digestibility compared with PA+SA. Treatment by production level interactions were observed for neutral detergent fiber (NDF) digestibility, total FA intake, and the yields of 3.5% fat-corrected milk (FCM), energy-corrected milk (ECM), and milk fat. In low-producing cows, FAT increased DM and NDF digestibility compared with CON. In high-producing cows PA+SA increased DM and NDF digestibility compared with PA+OA. In low-producing cows, PA+SA increased 3.5% FCM, ECM, and milk fat yield compared with PA+OA. However, in high-producing cows PA+OA tended to increase 3.5% FCM compared with PA+SA. In conclusion, low-producing cows responded better to a FA blend containing 60% C16:0 and 30% C18:0, whereas high-producing dairy cows responded more favorably to a FA blend containing 60% C16:0 and 30% cis-9 C18:1. However, further research is required to validate our observations that higher-yielding cows have improved production responses when supplemented with cis-9 C18:1 compared with C18:0.
Subject(s)
Milk , Palmitic Acid , Animal Feed/analysis , Animals , Cattle , Diet/veterinary , Dietary Supplements , Digestion , Fatty Acids , Female , Lactation , Nutrients , Oleic AcidABSTRACT
Objective: To examine how measures of infertility based on medical criteria and based on self-perception relate to depressive symptoms among women with infertility. Background: Survey-based studies of depressive symptoms have used either measures of self-reported infertility based on meeting medical criteria or measures of self-perceived fertility problems, but seldom both. It is, therefore, not known which type of measure is more closely associated with depressive symptoms. Materials and Methods: Using ordinary least-squares multiple regression, this study compares associations between a measure of meeting medical criteria for infertility and a measure of self-perceived fertility problems with a common measure of depressive symptoms. Data come from the National Survey of Fertility Barriers, a population-based survey of 4,711 U.S. women. Results: Both meeting medical criteria for infertility and self-perception were associated with depressive symptoms after controlling for a number of relevant variables, but the coefficient for the self-perception measure was slightly higher than the coefficient for medical criteria. Conclusion: If possible, both medical criteria and self-perception measures should be used in studies of the consequences of infertility for psychosocial outcomes. If only one measure can be used, self-perception of a fertility problem is an acceptable measure.
ABSTRACT
BACKGROUND: Many women who are at increased risk of breast cancer due to a mother or sister diagnosed with breast cancer aged under 40 do not currently qualify for surveillance before 40â¯years of age. There are almost no available data to assess whether mammography screening aged 35-39â¯years would be effective in this group, in terms of detection of breast cancer at an early stage or cost effective. METHODS: A cohort screening study (FH02) with annual mammography was devised for women aged 35-39 to assess the sensitivity and screening performance and potential survival of women with identified tumours. FINDINGS: 2899 women were recruited from 12/2006-12/2015. These women underwent 12,086 annual screening mammograms and were followed for 13,365.8â¯years. A total of 55 breast cancers in 54 women occurred during the study period (one bilateral) with 50 cancers (49 women) (15 CIS) adherent to the screening. Eighty percent (28/35) of invasive cancers were ≤ 2â¯cm and 80% also lymph node negative. Invasive cancers diagnosed in FH02 were significantly smaller than the comparable (POSH-unscreened prospective) study group (45% (131/293)â¯≤â¯2â¯cm in POSH vs 80% (28/35) in FH02 pâ¯<â¯0.0001), and were less likely to be lymph-node positive (54% (158/290, 3 unknown) in POSH vs 20% (7/35) in FH02: pâ¯=â¯0.0002. Projected and actual survival were also better than POSH. Overall radiation dose was not higher than in an older screened population at mean dose on study per standard sized breast of 1.5â¯mGy. INTERPRETATION: Mammography screening aged 35-39â¯years detects breast cancer at an early stage and is likely to be as effective in reducing mortality as in women at increased breast cancer risk aged 40-49â¯years.
ABSTRACT
BACKGROUND: Implantable cardioverter defibrillators (ICD) have been demonstrated to reduce mortality in survivors of life-threatening arrhythmias (secondary prevention) and in patients at increased risk of sudden cardiac death (primary prevention). Other nations have reported significant increases in ICD use in recent years. AIM: To investigate Australian nationwide trends of ICD procedures over a 10-year period (2000-2009). METHODS: A retrospective analysis of the Australian Institute of Health and Welfare's National Hospital Morbidity Database was performed to determine the annual number of ICD implantation and replacement procedures between 2000 and 2009. Rates were calculated using Australian Bureau of Statistics data on the annual estimated population. Time trends in the yearly procedure number and rate were analysed using negative binomial regression models with comparisons made by age and sex. RESULTS: The number of new ICD implantations increased from 708 to 3198 procedures between 2000 and 2009. Replacement procedures increased from 290 to 1378. The implantation rate (per million) increased from 37.0 to 145.6 and the replacement rate from 15.1 to 62.7. When rates were adjusted for age and sex, the implantation rate increased annually by 15.8% and the replacement rate by 16.6% (P < 0.0001). Procedures occurred most commonly in men (implantations: 80.1%; replacements: 78.0%) between ages 70-79. CONCLUSIONS: ICD procedures increased significantly in Australia between 2000-2009. Despite these increases, other studies have suggested ICD devices are currently under-utilised. During the study period, males accounted for the majority of ICD procedures. While there are numerous reasons for this, it is not known if device under-use is more common in females.
Subject(s)
Arrhythmias, Cardiac/epidemiology , Arrhythmias, Cardiac/therapy , Defibrillators, Implantable/statistics & numerical data , Defibrillators, Implantable/trends , Adult , Aged , Aged, 80 and over , Australia/epidemiology , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
Toll-like receptor 9 (TLR9) triggering is a promising novel strategy to combat cancer as it induces innate and adaptive immunity responses. B-cell lymphoma is unique in this context as tumor cells express TLR9 and may harbor latent Epstein-Barr virus (EBV), a gamma-herpesvirus with remarkable oncogenic potential when latent. Latent EBV may be promoted by TLR9 triggering via suppression of lytic EBV. Here, we elaborated an initial assessment of the impact of TLR9 triggering on EBV-positive and EBV-negative B-cell lymphoma using Burkitt's lymphoma (BL) cell lines as an in vitro model. We show that, independent of the presence of EBV, the TLR9 ligand oligodeoxynucleotide (ODN) CpG-2006 may or may not induce caspase-dependent cell death in BL cells. Moreover, ODN CpG-2006-induced cell death responses of BL cells were associated with TLR9 single-nucleotide polymorphisms (SNPs) rs5743836 or rs352140, which we detected in primary BL tumors and in peripheral blood from healthy individuals at similar frequencies. Thus, our findings suggest that the effect of TLR9 agonists on BL cells should be tested in vitro before installment of therapy and TLR9 SNPs in BL patients should be determined as potential biological markers for the therapeutic response to treatment targeting innate immunity.
Subject(s)
Burkitt Lymphoma/metabolism , Oligodeoxyribonucleotides/pharmacology , Polymorphism, Genetic , Toll-Like Receptor 9/agonists , Toll-Like Receptor 9/genetics , Adult , Aged , Burkitt Lymphoma/pathology , Burkitt Lymphoma/virology , Cell Death/drug effects , CpG Islands , Herpesvirus 4, Human/physiology , Humans , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Middle Aged , Receptors, Interleukin-1/genetics , Receptors, Interleukin-1/metabolismABSTRACT
According to EUSOMA position paper 'The requirements of a specialist breast unit', each breast unit should have a core team made up of health professionals who have undergone specialist training in breast cancer. In this paper, on behalf of EUSOMA, authors have identified the standards of training in breast cancer, to harmonise and foster breast care training in Europe. The aim of this paper is to contribute to the increase in the level of care in a breast unit, as the input of qualified health professionals increases the quality of breast cancer patient care.
Subject(s)
Breast Neoplasms/therapy , Education, Medical , Health Personnel/education , Medical Oncology/education , Education, Nursing/methods , Female , General Surgery/education , Humans , Nuclear Medicine/education , Radiology/educationABSTRACT
We investigated the effect of hypoxia on rat osteoblast function in long-term primary cultures. Reduction of pO2 from 20% to 5% and 2% decreased formation of mineralized bone nodules 1.7-fold and 11-fold, respectively. When pO2 was reduced further to 0.2%, bone nodule formation was almost abolished. The inhibitory effect of hypoxia on bone formation was partly due to decreased osteoblast proliferation, as measured by 3H-thymidine incorporation. Hypoxia also sharply reduced osteoblast alkaline phosphatase (ALP) activity and expression of mRNAs for ALP and osteocalcin, suggesting inhibition of differentiation to the osteogenic phenotype. Hypoxia did not increase the apoptosis of osteoblasts but induced a reversible state of quiescence. Transmission electron microscopy revealed that collagen fibrils deposited by osteoblasts cultured in 2% O2 were less organized and much less abundant than in 20% O2 cultures. Furthermore, collagen produced by hypoxic osteoblasts contained a lower percentage of hydroxylysine residues and exhibited an increased sensitivity to pepsin degradation. These data demonstrate the absolute oxygen requirement of osteoblasts for successful bone formation and emphasize the importance of the vasculature in maintaining bone health. We recently showed that hypoxia also acts in a reciprocal manner as a powerful stimulator of osteoclast formation. Considered together, our results help to explain the bone loss that occurs at the sites of fracture, tumors, inflammation and infection, and in individuals with vascular disease or anemia.
Subject(s)
Cell Differentiation/physiology , Hypoxia , Osteoblasts/physiology , Osteogenesis/physiology , Oxygen/metabolism , Alkaline Phosphatase/genetics , Alkaline Phosphatase/metabolism , Animals , Animals, Newborn , Biomarkers/metabolism , Cells, Cultured , Collagen/metabolism , Collagen/ultrastructure , Osteoblasts/cytology , Rats , Rats, Sprague-DawleyABSTRACT
The negative effect of acidosis on the skeleton has been known for almost a century. Bone mineral serves an important pathophysiologic role as a reserve of hydroxyl ions to buffer systemic protons if the kidneys and lungs are unable to maintain acid-base balance within narrow physiologic limits. Extracellular hydrogen ions are now thought to be the primary activation signal for osteoclastic bone resorption, and osteoclasts are very sensitive to small changes in pH within the pathophysiologic range. Herein, we investigated the effects of acidosis on osteoblast function by using mineralized bone nodule-forming primary osteoblast cultures. Osteoblasts harvested from neonatal rat calvariae were cultured up to 21 days in serum-containing medium, with ascorbate, beta-glycerophosphate and dexamethasone. pH was manipulated by addition of 5 to 30 mmol/L HCl and monitored by blood gas analyzer. Abundant, matrix-containing mineralized nodules formed in osteoblast cultures at pH 7.4, but acidification progressively reduced mineralization of bone nodules, with complete abolition at pH 6.9. Osteoblast proliferation and collagen synthesis, assessed by 3H-thymidine and 3H-proline incorporation, respectively, were unaffected by pH in the range 7.4 to 6.9; no effect of acidification on collagen ultrastructure and organization was evident. The apoptosis rate of osteoblasts, assessed by the enrichment of nucleosomes in cell lysates, was also unaffected by pH within this range. However, osteoblast alkaline phosphatase activity, which peaked strongly near pH 7.4, was reduced eight-fold at pH 6.9. Reducing pH to 6.9 also downregulated messenger ribonucleic acid (mRNA) for alkaline phosphatase, but upregulated mRNA for matrix Gla protein, an inhibitor of mineralization. The same pH reduction is associated with two-and four-fold increases in Ca2+ and PO4(3-) solubility for hydroxyapatite, respectively. Our results show that acidosis exerts a selective, inhibitory action on matrix mineralization that is reciprocal with the osteoclast activation response. Thus, in uncorrected acidosis, the deposition of alkaline mineral in bone by osteoblasts is reduced, and osteoclast resorptive activity is increased in order to maximize the availability of hydroxyl ions in solution to buffer protons.
Subject(s)
Acidosis/metabolism , Calcification, Physiologic/physiology , Extracellular Matrix/metabolism , Osteoblasts/metabolism , Osteogenesis/physiology , Alkaline Phosphatase/genetics , Alkaline Phosphatase/metabolism , Animals , Animals, Newborn , Apoptosis , Cell Proliferation , Cells, Cultured , Collagen/metabolism , Extracellular Matrix Proteins , Gene Expression Regulation , Hydrogen-Ion Concentration , Nucleosomes/metabolism , Osteoblasts/pathology , Osteocalcin/genetics , Osteocalcin/metabolism , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Skull/cytologyABSTRACT
The mean glandular doses (MGD) to samples of women attending for mammographic screening are measured routinely at screening centres in the UK Breast Screening Programme (NHSBSP). This paper reviews a large representative sample of dose measurements collected during screening in the NHSBSP in 2001 and 2002 for 53 218 films, using 290 X-ray sets, for 16 505 women. The average MGD was 2.23 mGy per oblique film and 1.96 mGy per craniocaudal film; similar to those found previously in the NHSBSP for the years 1997 and 1998. Increasing use of sophisticated units with automatic beam quality selection has reduced the radiation dose received by large breasts, with only 2% of oblique mammograms having doses in excess of 5 mGy. The increasing use of large format film has also reduced the doses to this sub-group. However the total dose per woman has increased due to the introduction of two view screening at every visit. The MGD to the standard breast was found to vary from 0.76 mGy to 2.29 mGy, with 97% of units below the recommended upper limit of 2 mGy, illustrating the benefit of strict quality control. A reduction in dose of 3% was observed between the age bands 50-54 years and 60-64 years. This study has confirmed that the proposed national diagnostic reference level (NDRL) of 3.5 mGy for 55 mm thick breasts is an appropriate value to identify systems giving unusually high doses, with just 3.5% of systems exceeding this level. In most cases these higher doses were explained by the design of one particular make of X-ray set and its mode of operation. Average doses for oblique views of average sized breasts were fairly well correlated with the dose to the standard breast, and typically 42% higher. This highlights the need for a revised definition of the standard breast used in the UK to better reflect the exposure factors and doses received in clinical practice.
Subject(s)
Breast Neoplasms/diagnostic imaging , Age Factors , Aged , Breast Neoplasms/pathology , Female , Humans , Mammography/methods , Mammography/statistics & numerical data , Mass Screening/methods , Mass Screening/statistics & numerical data , Middle Aged , Radiation Dosage , Reference Values , United KingdomSubject(s)
Escherichia coli Infections/veterinary , Goat Diseases/microbiology , Intestine, Small/pathology , Adhesins, Bacterial , Animals , Colon/microbiology , Colon/pathology , Diarrhea/etiology , Diarrhea/veterinary , Disease Outbreaks/veterinary , Escherichia coli Infections/microbiology , Escherichia coli Infections/pathology , Escherichia coli Proteins , Female , Gastrointestinal Contents/microbiology , Goat Diseases/pathology , Goats , Intestine, Small/microbiology , Intestine, Small/ultrastructure , Kidney/pathologyABSTRACT
During replication of herpes simplex virus type 1 (HSV-1), viral DNA is synthesized in the infected cell nucleus, where DNA-free capsids are also assembled. Genome-length DNA molecules are then cut out of a larger, multigenome concatemer and packaged into capsids. Here we report the results of experiments carried out to test the idea that the HSV-1 UL6 gene product (pUL6) forms the portal through which viral DNA passes as it enters the capsid. Since DNA must enter at a unique site, immunoelectron microscopy experiments were undertaken to determine the location of pUL6. After specific immunogold staining of HSV-1 B capsids, pUL6 was found, by its attached gold label, at one of the 12 capsid vertices. Label was not observed at multiple vertices, at nonvertex sites, or in capsids lacking pUL6. In immunoblot experiments, the pUL6 copy number in purified B capsids was found to be 14.8 +/- 2.6. Biochemical experiments to isolate pUL6 were carried out, beginning with insect cells infected with a recombinant baculovirus expressing the UL6 gene. After purification, pUL6 was found in the form of rings, which were observed in electron micrographs to have outside and inside diameters of 16.4 +/- 1.1 and 5.0 +/- 0.7 nm, respectively, and a height of 19.5 +/- 1.9 nm. The particle weights of individual rings as determined by scanning transmission electron microscopy showed a majority population with a mass corresponding to an oligomeric state of 12. The results are interpreted to support the view that pUL6 forms the DNA entry portal, since it exists at a unique site in the capsid and forms a channel through which DNA can pass. The HSV-1 portal is the first identified in a virus infecting a eukaryote. In its dimensions and oligomeric state, the pUL6 portal resembles the connector or portal complexes employed for DNA encapsidation in double-stranded DNA bacteriophages such as phi29, T4, and P22. This similarity supports the proposed evolutionary relationship between herpesviruses and double-stranded DNA phages and suggests the basic mechanism of DNA packaging is conserved.
Subject(s)
Capsid Proteins , Capsid/physiology , DNA, Viral/physiology , Virus Assembly , Amino Acid Sequence , Animals , Capsid/analysis , Capsid/chemistry , Chlorocebus aethiops , Microscopy, Electron , Molecular Sequence Data , Vero Cells , Viral ProteinsABSTRACT
Viral assembly is an ideal system in which to investigate the transient recognition and interplay between proteins. During morphogenesis, scaffolding proteins temporarily associate with structural proteins, stimulating conformational changes that promote assembly and inhibit off-pathway reactions. Microviridae morphogenesis is dependent on two scaffolding proteins, an internal and an external species. The external scaffolding protein is the most conserved protein within the Microviridae, whose canonical members are phiX174, G4, and alpha3. However, despite 70% homology on the amino acid level, overexpression of a foreign Microviridae external scaffolding protein is a potent cross-species inhibitor of morphogenesis. Mutants that are resistant to the expression of a foreign scaffolding protein cannot be obtained via one mutational step. To define the requirements for and constraints on scaffolding protein interactions, chimeric external scaffolding proteins have been constructed and analyzed for effects on in vivo assembly. The results of these experiments suggest that at least two cross-species inhibitory domains exist within these proteins; one domain most likely blocks procapsid formation, and the other allows procapsid assembly but blocks DNA packaging. A mutation conferring resistance to the expression of a chimeric protein (chiD(r)) that inhibits DNA packaging was isolated. The mutation maps to gene A, which encodes a protein essential for packaging. The chiD(r) mutation confers resistance only to a chimeric D protein; the mutant is still inhibited by the expression of foreign D proteins. The results presented here demonstrate how closely related proteins could be developed into antiviral agents that specifically target virion morphogenesis.
Subject(s)
Bacteriophage phi X 174/physiology , Recombinant Fusion Proteins/physiology , Viral Structural Proteins/physiology , Amino Acid Sequence , Molecular Sequence Data , Morphogenesis , Virus AssemblyABSTRACT
Microviridae morphogenesis is dependent on two scaffolding proteins, an internal and external species. Both structural and genetic analyses suggest that the COOH-terminus of the internal protein is critical for coat protein recognition and specificity. To test this hypothesis, chimeric internal scaffolding genes between Microviridae members phiX174, G4, and alpha3 were constructed and the proteins expressed in vivo. All of the chimeric proteins were functional in complementation assays. However, the efficient complementation was observed only when the viral coat protein and COOH-terminus of internal scaffolding were of the same origin. Genes with 5' deletions of the phiX174 internal scaffolding gene were also constructed and expressed in vivo. Proteins lacking the first 10 amino acids, which self-associate across the twofold axes of symmetry in the atomic structure, efficiently complement phiX174 am(B) mutants at temperatures above 24 degrees C. These results suggest that internal scaffolding protein self-associations across the twofold axes of symmetry are required only at lower temperatures.
Subject(s)
Microviridae/metabolism , Recombinant Fusion Proteins/metabolism , Viral Structural Proteins , Viral Structural Proteins/metabolism , Genes, Viral , Microviridae/genetics , Protein Folding , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/genetics , Sequence Deletion , Viral Structural Proteins/chemistry , Viral Structural Proteins/geneticsABSTRACT
The mean glandular doses (MGDs) to samples of women attending for mammographic screening are measured routinely at screening centres in the UK Breast Screening Programme (NHSBSP). This paper reviews the data collected during screening in the NHSBSP in 1997 and 1998 for 23,752 films, using 171 X-ray sets, for 8745 women. Average MGD was 2.03 mGy per oblique film and 1.65 mGy per craniocaudal film, similar to the MGDs found previously in the NHSBSP for the years 1994 and 1995. MGD was found to increase with compressed breast thickness where the tube potential was selected manually, so that the average dose for 10 cm thick breasts was 2.7 times the average for all breasts. For large breasts (> 70 mm) the use of X-ray sets such as the IGE DMR, which automatically select the beam quality for each breast, resulted in lower doses compared with sets using manual tube potential selection. MGD to the standard breast was found to vary from 0.7 to 2.2 mGy and to be correlated with the average MGD per mediolateral oblique film for the women screened on that system (R = 0.79). No correlation between age and MGD was found within the invited age range of 50-64 years.
Subject(s)
Breast Neoplasms/diagnostic imaging , Mass Screening/standards , Age Factors , Breast/anatomy & histology , Female , Humans , Mammography , Middle Aged , Quality Control , Radiation DosageABSTRACT
An empty precursor particle called the procapsid is formed during assembly of the single-stranded DNA bacteriophage phiX174. Assembly of the phiX174 procapsid requires the presence of the two scaffolding proteins, D and B, which are structural components of the procapsid, but are not found in the mature virion. The X-ray crystallographic structure of a "closed" procapsid particle has been determined to 3.5 A resolution. This structure has an external scaffold made from 240 copies of protein D, 60 copies of the internally located B protein, and contains 60 copies of each of the viral structural proteins F and G, which comprise the shell and the 5-fold spikes, respectively. The F capsid protein has a similar conformation to that seen in the mature virion, and differs from the previously determined 25 A resolution electron microscopic reconstruction of the "open" procapsid, in which the F protein has a different conformation. The D scaffolding protein has a predominantly alpha-helical fold and displays remarkable conformational variability. We report here an improved and refined structure of the closed procapsid and describe in some detail the differences between the four independent D scaffolding proteins per icosahedral asymmetric unit, as well as their interaction with the F capsid protein. We re-analyze and correct the comparison of the closed procapsid with the previously determined cryo-electron microscopic image reconstruction of the open procapsid and discuss the major structural rearrangements that must occur during assembly. A model is proposed in which the D proteins direct the assembly process by sequential binding and conformational switching.
Subject(s)
Bacteriophage phi X 174/metabolism , Capsid/metabolism , Amino Acid Sequence , Capsid/chemistry , Crystallography, X-Ray , Microscopy, Electron , Models, Molecular , Molecular Sequence Data , Protein Conformation , Virus AssemblyABSTRACT
The assembly of the viral structural proteins into infectious virions is often mediated by scaffolding proteins. These proteins are transiently associated with morphogenetic intermediates but not found in the mature particle. The genes encoding three Microviridae (phiX174, G4 and alpha3) internal scaffolding proteins (B proteins) have been cloned, expressed in vivo and assayed for the ability to complement null mutations of different Microviridae species. Despite divergence as great as 70% in amino acid sequence over the aligned length, cross-complementation was observed, indicating that these proteins are capable of directing the assembly of foreign structural proteins into infectious particles. These results suggest that the Microviridae internal scaffolding proteins may be inherently flexible. There was one condition in which a B protein could not cross-function. The phiX174 B protein cannot productively direct the assembly of the G4 capsid at temperatures above 21 degreesC. Under these conditions, assembly is arrested early in the morphogenetic pathway, before the first B protein mediated reaction. Two G4 mutants, which can productively utilize the phiX174 B protein at elevated temperatures, were isolated. Both mutations confer amino acid substitutions in the viral coat protein but differ in their relative abilities to utilize the foreign scaffolding protein. The more efficient substitution is located in a region where coat-scaffolding interactions have been observed in the atomic structure and may emphasize the importance of interactions in this region.
Subject(s)
Microviridae/physiology , Viral Proteins/chemistry , Amino Acid Sequence , Bacteriophage phi X 174/genetics , Bacteriophage phi X 174/physiology , DNA-Binding Proteins/chemistry , Escherichia coli/virology , Molecular Sequence Data , Sequence Homology, Amino Acid , Viral Proteins/physiology , Virus AssemblyABSTRACT
OBJECTIVE: To determine age- and sex-adjusted reference ranges (ASARRs) for glomerular filtration status using data from nondiabetic subjects and to apply these to newly presenting type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: Glomerular filtration rate corrected for body surface area (cGFR) was determined using a radionuclide (51Cr-EDTA) method in 75 non-diabetic subjects (37 men, 38 women) and 219 type 2 diabetic subjects (157 men, 62 women). The 95% constant reference ranges (CRRs) were calculated as mean nondiabetic cGFR+/-1.96 SD. The 95% ASARRs were calculated by Altman's method from the nondiabetic cGFR versus age regression residuals for both male and female subjects. RESULTS: Using Altman's method, the intercepts, but not the gradients, of the cGFR versus age regressions were significantly different between male and female subjects (intercept difference [95% CI] 8.2 [1.3-15.1], gradient difference -0.4 [-1.1 to 0.3]). Fitting a common gradient, 95% ASARRs for normofiltration were found to be from 123.9 - (0.89 X age) to 181.7 - (0.89 x age) for male subjects, and from 116.0 - (0.89 X age) to 173.2 - (0.89 X age) for female subjects. The 95% CRR for normofiltration was 70.2-138.1 ml x min(-1) x (1.73 m)(-2). When applied to the diabetic cGFRs, the CRRs and ASARRs gave, respectively, 17% (37/219) versus 21% (46/219) hyperfiltrators and 83% (181/219) versus 79% (172/219) normofiltrators. Using the ASARRs, 14 normofiltrators (6 men, 8 women) were reclassified as hyperfiltrators (change [n/total n] [95% CI] 8% [14/181] [4-12]), and 5 hyperfiltrators (5 men, 0 women) were reclassified as normofiltrators (change 14% [5/37] [5-30]). CONCLUSIONS: We conclude that age and sex adjustment are essential to assess glomerular filtration status.
Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Kidney Glomerulus/physiopathology , Adult , Age Factors , Aged , Female , Glomerular Filtration Rate , Humans , Male , Middle Aged , Reference Values , Sex FactorsABSTRACT
A survey of radiation dose and compressed breast thickness was conducted in samples of women undergoing mammography in the United Kingdom National Health Service breast screening programme. The aims were to determine the average value and distribution of dose and thickness, and to identify technical difficulties in carrying out such a survey. Values of breast thickness and mean glandular dose, calculated from exposure factors and measured X-ray beam parameters, were collected for 4633 women in 92 screening units in 1994 and 1995. The median (lower quartile, upper quartile) dose per film was 1.7 (1.2, 2.4) mGy for the mediolateral oblique view (mean thickness 57 mm) and 1.4 (1.1, 2.0) mGy for the craniocaudal view (mean thickness 52 mm). The median dose per woman was 1.8 (1.3, 2.5) mGy for a one-view examination and 3.3 (2.3, 4.6) mGy for a two-view examination. The dose per film showed an exponential relationship to breast thickness, but no relationship was found between median dose and median breast thickness in the different screening units, possibly because of errors in breast thickness measurement. The values of breast thickness and dose were generally consistent with those in other published surveys, allowing for differences in radiographic technique. No relationship between breast dose and standard optical density was demonstrated. Some recommendations for the conduct of future surveys of breast dose in the UK are proposed.
Subject(s)
Breast Neoplasms/diagnostic imaging , Breast/radiation effects , Mammography , Mass Screening , Radiation Dosage , Breast/anatomy & histology , Breast Neoplasms/prevention & control , Female , Health Care Surveys/methods , Humans , Mammography/adverse effects , Mammography/standards , Middle Aged , Pilot Projects , United KingdomABSTRACT
This study examined visual analog scaling (VAS) judgments of disfluency by normal listeners in response to oral reading by speakers with spasmodic dysphonia (SD) and by nondysphonic controls, as well as the variables of frequency of occurrence of disfluencies, speaking rate, number of reading errors, and temporal acoustic measures of interword interval duration and articulation time. MANOVA yielded statistically significant differences between SD and control speakers for all variables except reading errors. Although no significant fluency-related differences were observed in terms of type of vocal spasm or voice tremor, significant differences in disfluency measures were obtained for clinical ratings of severity of dysphonia. Greater dysphonia severity ratings were associated with decreased fluency, but milder ratings were not necessarily associated with disfluency. Stepwise multiple regression analysis demonstrated that frequency of disfluency occurrence, speaking rate, and reading errors accounted for more than three fourths of the variability in VAS judgments of disfluency. Findings suggest that although disfluency is not a defining feature of SD, it does contribute significantly to the overall clinical impression of severity of the disorder.