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1.
Dis Aquat Organ ; 135(1): 1-31, 2019 Jun 20.
Article in English | MEDLINE | ID: mdl-31219432

ABSTRACT

Seventy mortalities of North Atlantic right whales Eubalaena glacialis (NARW) were documented between 2003 and 2018 from Florida, USA, to the Gulf of St. Lawrence, Canada. These included 29 adults, 14 juveniles, 10 calves, and 17 of unknown age class. Females represented 65.5% (19/29) of known-sex adults. Fourteen cases had photos only; 56 carcasses received external examinations, 44 of which were also necropsied. Cause of death was determined in 43 cases, of which 38 (88.4%) were due to anthropogenic trauma: 22 (57.9%) from entanglement, and 16 (42.1%) from vessel strike. Gross and histopathologic lesions associated with entanglement were often severe and included deep lacerations caused by constricting line wraps around the flippers, flukes, and head/mouth; baleen plate mutilation; chronic extensive bone lesions from impinging line, and traumatic scoliosis resulting in compromised mobility in a calf. Chronically entangled whales were often in poor body condition and had increased cyamid burden, reflecting compromised health. Vessel strike blunt force injuries included skull and vertebral fractures, blubber and muscle contusions, and large blood clots. Propeller-induced wounds often caused extensive damage to blubber, muscle, viscera, and bone. Overall prevalence of NARW entanglement mortalities increased from 21% (1970-2002) to 51% during this study period. This demonstrates that despite mitigation efforts, entanglements and vessel strikes continue to inflict profound physical trauma and suffering on individual NARWs. These cumulative mortalities are also unsustainable at the population level, so urgent and aggressive intervention is needed to end anthropogenic mortality in this critically endangered species.


Subject(s)
Endangered Species , Whales , Animals , Atlantic Ocean , Canada , Female , Florida
2.
Osteoporos Int ; 28(9): 2675-2682, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28612306

ABSTRACT

The primary objective is the description of bone mineral density (BMD) and body composition in newly licensed jockeys. One in three male, flat jockeys has a very low bone mineral density. Further research is needed to assess the short-term risk of fractures and long-term health implications of these findings. INTRODUCTION: Describe bone mineral density (BMD) and body composition in entry-level male and female, flat and jump jockeys in Great Britain. METHODS: Data was collected on jockeys applying for a professional jockey license between 2013 and 2015. Areal BMD at the spine, femoral neck (FN), total hip and body composition were assessed by dual-energy X-ray absorptiometry (DXA) scan. We examined differences between BMD and body composition by gender and race type (flat or jump). Volumetric bone mineral apparent density (BMAD) of the spine and FN was also calculated to account for group differences in bone size. RESULTS: Seventy-nine male flat jockeys (age 18.5 ± 1.9, BMI 19.0 ± 1.4), 69 male jump (age 20.7 ± 2.0, BMI 20.6 ± 1.3) and 37 female flat jockeys (age 19.3 ± 2.0, BMI 20.8 ± 1.7) took part in this study. Spine BMD Z-scores ≤-2 for male flat, male jump and female flat jockeys were 29, 13 and 2.7%, respectively. Spine BMD was lower in male than female flat jockeys (p<0.001). All BMD scores were lower in male flat compared to male jump jockeys (p<0.001). Body fat percent (BF %) was lower in male flat jockeys compared to male jump and female flat jockeys (p<0.05). Lean mass index (LMI) was lower in male flat compared to male jump jockeys (p<0.001). CONCLUSIONS: Male flat jockeys had a significantly lower BMD, LMI and BF% compared to jump jockeys and female flat jockeys. Male flat jockeys had lower spine BMD scores than females. Individual bone maturation may influence these findings. Further investigation into the relevance of low BMD and altered body composition on jockey health is required.


Subject(s)
Body Composition/physiology , Bone Density/physiology , Occupational Health , Sports/physiology , Absorptiometry, Photon/methods , Adolescent , Anthropometry/methods , Body Mass Index , Female , Femur Neck/physiology , Hip Joint/physiology , Humans , Lumbar Vertebrae/physiology , Male , Sex Characteristics , Young Adult
3.
Epidemiol Infect ; 145(5): 848-856, 2017 04.
Article in English | MEDLINE | ID: mdl-28065170

ABSTRACT

Whole apples have not been previously implicated in outbreaks of foodborne bacterial illness. We investigated a nationwide listeriosis outbreak associated with caramel apples. We defined an outbreak-associated case as an infection with one or both of two outbreak strains of Listeria monocytogenes highly related by whole-genome multilocus sequence typing (wgMLST) from 1 October 2014 to 1 February 2015. Single-interviewer open-ended interviews identified the source. Outbreak-associated cases were compared with non-outbreak-associated cases and traceback and environmental investigations were performed. We identified 35 outbreak-associated cases in 12 states; 34 (97%) were hospitalized and seven (20%) died. Outbreak-associated ill persons were more likely to have eaten commercially produced, prepackaged caramel apples (odds ratio 326·7, 95% confidence interval 32·2-3314). Environmental samples from the grower's packing facility and distribution-chain whole apples yielded isolates highly related to outbreak isolates by wgMLST. This outbreak highlights the importance of minimizing produce contamination with L. monocytogenes. Investigators should perform single-interviewer open-ended interviews when a food is not readily identified.


Subject(s)
Disease Outbreaks , Foodborne Diseases/epidemiology , Listeria monocytogenes/isolation & purification , Listeriosis/epidemiology , Malus/microbiology , Candy/microbiology , Carbohydrates , Foodborne Diseases/microbiology , Genotype , Interviews as Topic , Listeria monocytogenes/classification , Listeria monocytogenes/genetics , Listeriosis/microbiology , Multilocus Sequence Typing , Survival Analysis , United States/epidemiology
4.
Epidemiol Infect ; 144(13): 2698-708, 2016 10.
Article in English | MEDLINE | ID: mdl-26122394

ABSTRACT

Listeria monocytogenes is a foodborne pathogen that can cause bacteraemia, meningitis, and complications during pregnancy. In July 2012, molecular subtyping identified indistinguishable L. monocytogenes isolates from six patients and two samples of different cut and repackaged cheeses. A multistate outbreak investigation was initiated. Initial analyses identified an association between eating soft cheese and outbreak-related illness (odds ratio 17·3, 95% confidence interval 2·0-825·7) but no common brand. Cheese inventory data from locations where patients bought cheese and an additional location where repackaged cheese yielded the outbreak strain were compared to identify cheeses for microbiological sampling. Intact packages of imported ricotta salata yielded the outbreak strain. Fourteen jurisdictions reported 22 cases from March-October 2012, including four deaths and a fetal loss. Six patients ultimately reported eating ricotta salata; another reported eating cheese likely cut with equipment also used for contaminated ricotta salata, and nine more reported eating other cheeses that might also have been cross-contaminated. An FDA import alert and US and international recalls followed. Epidemiology-directed microbiological testing of suspect cheeses helped identify the outbreak source. Cross-contamination of cheese highlights the importance of using validated disinfectant protocols and routine cleaning and sanitizing after cutting each block or wheel.


Subject(s)
Cheese/microbiology , Disease Outbreaks , Food Microbiology , Foodborne Diseases/epidemiology , Listeria monocytogenes/isolation & purification , Listeriosis/epidemiology , Adult , Aged , Aged, 80 and over , Female , Foodborne Diseases/microbiology , Foodborne Diseases/mortality , Humans , Listeria monocytogenes/classification , Listeriosis/microbiology , Listeriosis/mortality , Male , Middle Aged , Pregnancy , United States/epidemiology
5.
J Dairy Sci ; 95(12): 7210-3, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23040028

ABSTRACT

A challenge model for experimentally inducing Streptococcus uberis mastitis in bred dairy heifers was developed. Qualifying heifers (n=7) exhibited antibody titers of <1:10,000 against Strep. uberis antigens and were free of intramammary infections (IMI). Two contralateral quarters of each heifer were assigned to receive an infusion of Strep. uberis (1,000 to 2,000 cfu); remaining quarters served as unchallenged controls. For a successful challenge and infection, 3 of 4 consecutive mammary secretion samples had to culture positive for Strep. uberis. Six of the 7 heifers were challenged successfully in both infused quarters with a mean dose of 1,080 cfu; once confirmed, infections were treated with a one-time infusion of nonlactating cow therapy. Before challenge, mammary secretion leukocyte counts averaged 8.4×10(6)/mL in all quarters. At 24h after challenge, leukocyte count increased to 18.4×10(6)/mL in challenged quarters, peaking on d 5 at 24.3×10(6)/mL; unchallenged quarters remained at ≤10.4×10(6)/mL, but increased to 15.2×10(6)/mL on d 7 and then decreased. Before challenge, macrophages predominated (81%) in mammary secretions followed by lymphocytes (15.3%) and neutrophils (3.7%). By 24h after challenge, neutrophils increased in challenged quarters and predominated for the duration of the trial (65.3 to 70%), whereas macrophages predominated in unchallenged control quarters (65.2 to 75.2%). The challenge model was successful in establishing Strep. uberis IMI in 85.7% of animals, and IMI were controlled (100% cure) by administering nonlactating cow therapy. All heifers calved free of IMI and antimicrobial residues, with milk production similar to that of herd mates and with somatic cell counts (SCC) <200,000 cells/mL.


Subject(s)
Mastitis, Bovine/microbiology , Streptococcal Infections/veterinary , Streptococcus/pathogenicity , Animals , Cattle , Disease Models, Animal , Female , Leukocyte Count/veterinary , Mammary Glands, Animal/immunology , Mammary Glands, Animal/microbiology , Mastitis, Bovine/immunology , Streptococcal Infections/immunology , Streptococcal Infections/microbiology
6.
Epidemiol Infect ; 138(10): 1503-9, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20158931

ABSTRACT

Infection by Listeria monocytogenes in pregnant women may result in fetal loss or invasive disease in the newborn. We examined listeriosis cases reported through the U.S. Listeria Initiative during 2004-2007. Cases were classified as pregnancy-associated if illness occurred in a pregnant woman or an infant aged <28 days. Of 758 reported Listeria cases, 128 (16.9%) were pregnancy-associated. Maternal infection resulted in four neonatal deaths and 26 (20.3%) fetal losses. Invasive illnesses in newborns (n=85) were meningitis (32.9%) and sepsis (36.5%). Pregnant women with Listeria were more likely to report Hispanic ethnicity (52.8% vs. 25.6%, respectively; OR 3.3 95% CI 2.2-4.8) than mothers giving live birth in the USA during 2005 and were more likely to report consumption of Mexican-style cheese (OR 2.6, 95% CI 1.6-4.2) than were non-pregnant patients with Listeria infection. Pregnant woman comprised a considerable proportion of reported listeriosis cases. Further declines in pregnancy-associated listeriosis will require education about avoiding high-risk foods, and continued regulatory and industry efforts to decrease Listeria in foods.


Subject(s)
Infant, Newborn, Diseases/epidemiology , Listeria monocytogenes/isolation & purification , Listeriosis/epidemiology , Pregnancy Complications, Infectious/epidemiology , Adolescent , Adult , Ethnicity , Feeding Behavior , Female , Foodborne Diseases/epidemiology , Foodborne Diseases/microbiology , Humans , Incidence , Infant, Newborn , Infant, Newborn, Diseases/microbiology , Infant, Newborn, Diseases/mortality , Listeriosis/microbiology , Middle Aged , Pregnancy , Pregnancy Complications, Infectious/microbiology , Risk Factors , United States/epidemiology , Young Adult
7.
J Chem Phys ; 132(6): 064306, 2010 Feb 14.
Article in English | MEDLINE | ID: mdl-20151742

ABSTRACT

Computed electron removal energies for Cu(N) (-) clusters, N=9-20, are presented for the three lowest-energy isomers obtained from extensive, unbiased searches for the minimum energy structure at each size. The density functional theory (DFT) computations make use of a scheme introduced by Jellinek and Acioli (JA) [J. Chem. Phys. 118, 7783 (2003)] that obtains electron removal energies from DFT orbital energies using corrections based on DFT total energies. The computed removal energies are compared with the measured photoelectron spectra (PES) for Cu(N) (-). The patterns of computed removal energies are shown to be isomer specific for clusters in this size range. By matching the computed removal energies to the observed PES, the isomers responsible for the PES are identified. The results of the JA scheme are compared to those obtained using other DFT-based methods.


Subject(s)
Copper/chemistry , Electrons , Isomerism , Models, Molecular , Molecular Structure , Photoelectron Spectroscopy , Quantum Theory
8.
Eur J Clin Nutr ; 62(4): 537-43, 2008 Apr.
Article in English | MEDLINE | ID: mdl-17375109

ABSTRACT

OBJECTIVE: To determine the minimum number of days of dietary intake interviews required to reduce the effects of random error (day-to-day variability in dietary intake) when using the multiple-pass, multiple-day, 24-h recall method. DESIGN: Cross-sectional study. SETTING: University research department. SUBJECTS: A total of 50 healthy non-smoking overweight and obese (body mass index=26-40 kg/m2) adult men and women aged 39-45 years completed the study. Participants were randomly selected from volunteers for a larger unrelated study. INTERVENTIONS: Each participant completed 10, multiple-pass, 24-h recall interviews on randomly chosen days over 4 weeks. The minimum number of record days was determined for each macronutrient (carbohydrate, fat, protein) and energy, for each gender, to obtain a 'true' (unobservable) representative intake from reported (observed) dietary intakes. RESULTS: The greatest number of days required to obtain a 'true' representative intake was 8 days. Carbohydrate intakes required the greatest number of days of dietary record among males (7 days), whereas protein required the greatest number of days among females (8 days) in this cohort. Sunday was the day of the week that showed greatest variability in macronutrient intakes. Protein (P<0.05) and fat (P<0.001) intakes were significantly more variable than carbohydrate on Sundays compared with weekdays, for both men and women. CONCLUSION: A logistically achievable 8 days of dietary intake interviews was sufficient to minimize the effect of random error when using the multiple-pass, 24-h recall dietary intake method. Sunday should be included among the dietary interview days to ensure a 'true' representation of macronutrient intakes. This method can be confidently applied to small cohort studies in which dietary intakes from different groups are to be compared or to investigations of associations between nutrient intakes and disease.


Subject(s)
Energy Intake/physiology , Mental Recall , Nutrition Assessment , Obesity/psychology , Overweight/psychology , Adult , Body Mass Index , Cohort Studies , Cross-Sectional Studies , Diet Surveys , Dietary Carbohydrates/administration & dosage , Dietary Fats/administration & dosage , Dietary Proteins/administration & dosage , Female , Humans , Male , Reproducibility of Results , Sensitivity and Specificity , Sex Distribution , Time Factors
9.
J Clin Invest ; 107(11): 1395-402, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11390421

ABSTRACT

Myocyte loss in the ischemically injured mammalian heart often leads to irreversible deficits in cardiac function. To identify a source of stem cells capable of restoring damaged cardiac tissue, we transplanted highly enriched hematopoietic stem cells, the so-called side population (SP) cells, into lethally irradiated mice subsequently rendered ischemic by coronary artery occlusion for 60 minutes followed by reperfusion. The engrafted SP cells (CD34(-)/low, c-Kit(+), Sca-1(+)) or their progeny migrated into ischemic cardiac muscle and blood vessels, differentiated to cardiomyocytes and endothelial cells, and contributed to the formation of functional tissue. SP cells were purified from Rosa26 transgenic mice, which express lacZ widely. Donor-derived cardiomyocytes were found primarily in the peri-infarct region at a prevalence of around 0.02% and were identified by expression of lacZ and alpha-actinin, and lack of expression of CD45. Donor-derived endothelial cells were identified by expression of lacZ and Flt-1, an endothelial marker shown to be absent on SP cells. Endothelial engraftment was found at a prevalence of around 3.3%, primarily in small vessels adjacent to the infarct. Our results demonstrate the cardiomyogenic potential of hematopoietic stem cells and suggest a therapeutic strategy that eventually could benefit patients with myocardial infarction.


Subject(s)
Endothelium, Vascular/cytology , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells/physiology , Myocardial Ischemia/physiopathology , Myocardium/cytology , Regeneration/physiology , Animals , Bone Marrow/radiation effects , Endothelium, Vascular/metabolism , Humans , Immunohistochemistry , Mice , Mice, Inbred C57BL , Mice, Transgenic , Myocardial Infarction/pathology , Myocardial Ischemia/pathology , Myocardial Ischemia/therapy , Myocardium/metabolism , beta-Galactosidase/metabolism
10.
Placenta ; 28(5-6): 437-44, 2007.
Article in English | MEDLINE | ID: mdl-16914197

ABSTRACT

The aim of the study was to determine if the expression of zinc transporters in the mouse placenta is regulated by dietary zinc, commensurate with regulating the supply of zinc to the fetus. Mice were fed diets differing only in the concentration of zinc (moderately zinc-restricted (ZnR)--15 mg Zn/kg; zinc-adequate (ZnA)--50 mg Zn/kg; zinc-supplemented (ZnS)--150 mg Zn/kg) from the onset of pregnancy until collection of tissue at day 17. Compared with mice fed the other diets, fetal weight was reduced in the ZnR group and total non-embryonic weight gain was reduced in mice fed the ZnS diet. Transcript levels of metallothionein and the zinc transporters ZnT1, ZnT4 and ZIP1 were reduced in the placenta of mice fed both the ZnR and ZnS diets compared with mice fed the ZnA diet. Placental ZnT7 and fetal liver metallothionein transcript levels did not differ significantly between mice fed the three diets and placental ZnT5 was reduced in mice fed the ZnS compared with the ZnA diet but did not differ significantly between the ZnA and ZnR diets. The pattern of mRNA expression in placenta was reflected at the protein level for ZnT1. Levels of ZnT5 protein were also highest in mice fed the ZnA diet. Both ZnT1 and ZnT5 were detected in the human villous syncytiotrophoblast by immunohistochemistry. The data indicate that the expression of zinc transporters in mouse placenta is responsive to dietary zinc supply but this modulation of expression is insufficient to maintain optimum fetal nutrition at even a modest level of dietary zinc restriction.


Subject(s)
Carrier Proteins/metabolism , Cation Transport Proteins/genetics , Placenta/physiology , Zinc/pharmacology , Animals , Dietary Supplements , Female , Membrane Transport Proteins/genetics , Metallothionein/genetics , Mice , Placenta/drug effects , Pregnancy , Transcription, Genetic , Zinc/deficiency
11.
Metallomics ; 8(3): 337-43, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26824222

ABSTRACT

Only a small number of genes are known direct targets of the zinc-responsive transcription factor MTF1; therefore, the aim of this study was to gain a more complete understanding of the MTF-1 regulated zinc-responsive component of the transcriptome. A targeted siRNA was used to deplete MTF1 expression in the human intestinal cell line Caco-2. We predicted that the response to zinc of direct MTF1 target genes would be abrogated by MTF1 knockdown. Surprisingly, a greater number of genes were regulated by zinc following MFT1 knockdown, and most genes that responded to zinc under both control and MTF1-depleted conditions had an augmented response in the latter condition. Exceptions were the zinc effluxer ZnT1 and a suite of metallothionein genes, suggesting that responses of other genes to zinc are usually buffered by increases in these proteins. We propose that MTF1 heads a hierarchy of zinc sensors, and through controlling the expression of a raft of metallothioneins and other key proteins involved in controlling intracellular zinc levels (e.g. ZnT1) alters zinc buffering capacity and total cellular zinc content. We tested and validated this model by overexpressing metallothionein and observing the predicted curtailment in response of the zinc-repressed SLC30A5 (ZnT5) promoter. The model provides the framework for an integrated understanding of cellular zinc homeostasis. Because MTs can bind metals other than zinc, this framework links with overall cellular metal homeostasis.


Subject(s)
Cation Transport Proteins/metabolism , DNA-Binding Proteins/metabolism , Metallothionein/metabolism , Transcription Factors/metabolism , Transcriptome/genetics , Zinc/pharmacology , Caco-2 Cells , Cation Transport Proteins/genetics , Gene Deletion , Gene Expression Profiling , Gene Expression Regulation/drug effects , Gene Knockdown Techniques , Humans , Metallothionein/genetics , Multigene Family , Oligonucleotide Array Sequence Analysis , Promoter Regions, Genetic/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reproducibility of Results , Transcriptome/drug effects , Transcription Factor MTF-1
12.
J Food Prot ; 79(5): 806-9, 2016 05.
Article in English | MEDLINE | ID: mdl-27296429

ABSTRACT

We report on a case of listeriosis in a patient who probably consumed a prepackaged romaine lettuce-containing product recalled for Listeria monocytogenes contamination. Although definitive epidemiological information demonstrating exposure to the specific recalled product was lacking, the patient reported consumption of a prepackaged romaine lettuce-containing product of either the recalled brand or a different brand. A multinational investigation found that patient and food isolates from the recalled product were indistinguishable by pulsed-field gel electrophoresis and were highly related by whole genome sequencing, differing by four alleles by whole genome multilocus sequence typing and by five high-quality single nucleotide polymorphisms, suggesting a common source. To our knowledge, this is the first time prepackaged lettuce has been identified as a likely source for listeriosis. This investigation highlights the power of whole genome sequencing, as well as the continued need for timely and thorough epidemiological exposure data to identify sources of foodborne infections.


Subject(s)
Foodborne Diseases , Lactuca , Electrophoresis, Gel, Pulsed-Field , Food Microbiology , Humans , Listeria monocytogenes/genetics , Listeriosis
13.
BMJ Open ; 5(9): e007609, 2015 Sep 29.
Article in English | MEDLINE | ID: mdl-26419679

ABSTRACT

OBJECTIVE: Hip pain and injury as a result of activity can lead to the development of early hip osteoarthritis (OA) in susceptible individuals. Our understanding of the factors that increase susceptibility continues to evolve. The ability to clearly identify individuals (and cohorts) with activity-related hip pain who are at risk of early hip OA is currently lacking. The purpose of this study was to gain expert consensus on which key clinical measures might help predict the risk of early hip OA in individuals presenting with activity-related hip pain. The agreed measures would constitute a standardised approach to initial clinical assessment to help identify these individuals. METHODS: This Dephi study used online surveys to gain concordance of expert opinion in a structured process of 'rounds'. In this study, we asked 'What outcome measures are useful in predicting hip OA in activity-related hip pain?' The Delphi panel consisted of experts from sport and exercise medicine, orthopaedics, rheumatology, physiotherapy and OA research. RESULTS: The study identified key clinical measures in the history, examination and investigations (plain anteroposterior radiograph and femoroacetabular impingement views) that the panel agreed would be useful in predicting future risk of hip OA when assessing activity-related hip pain. The panel also agreed that certain investigations and tests (eg, MR angiography) did not currently have a role in routine assessment. There was a lack of consensus regarding the role of MRI, patient-reported outcome measures (PROMs) and certain biomechanical and functional assessments. CONCLUSIONS: We provide a standardised approach to the clinical assessment of patients with activity-related hip pain. Assessment measures rejected by the Delphi panel were newer, more expensive investigations that currently lack evidence. Assessment measures that did not reach consensus include MRI and PROMs. Their role remains ambiguous and would benefit from further research.


Subject(s)
Arthralgia/etiology , Hip Joint , Motor Activity , Osteoarthritis, Hip/diagnosis , Adult , Aged , Aged, 80 and over , Delphi Technique , Female , Humans , Male , Middle Aged , Osteoarthritis, Hip/etiology , Risk Assessment , Risk Factors
14.
Am J Clin Nutr ; 50(5): 980-2, 1989 Nov.
Article in English | MEDLINE | ID: mdl-2816805

ABSTRACT

Breast-milk lipids contain long-chain polyunsaturated fatty acids (PUFA) not found in infant formulas. Because the erythrocyte membranes of formula-fed infants are depleted in long-chain PUFA, we sought food sources of these 20- and 22-carbon polyunsaturates suitable for use as dietary supplements. A variety of commercially available infant foods containing meats and egg products in addition to some whole foods (meat, eggs) were analyzed by gas chromatography. Commercially available infant foods contained only low levels of long-chain PUFA. The richest source of omega-3 and omega-6 PUFA was found to be lamb brains but lamb and chicken livers as well as egg yolks also contained high levels. However, the lipid content of most whole foods including brains, eggs, and liver is so low that prohibitively large amounts of food would be required to be fed to infants. It is concluded that it is virtually impossible to supplement the diet of formula-fed infants to match the long-chain PUFA intake of breast-fed infants with currently available whole foods.


Subject(s)
Breast Feeding , Fatty Acids, Unsaturated/analysis , Infant Food/analysis , Infant Nutritional Physiological Phenomena , Milk, Human/analysis , Erythrocyte Membrane/metabolism , Humans , Infant , Membrane Lipids/metabolism , Nutritional Requirements
15.
Neuroscience ; 91(4): 1557-64, 1999.
Article in English | MEDLINE | ID: mdl-10391459

ABSTRACT

Episodic ataxia type 1 is a rare, autosomal dominant neurological disorder caused by missense mutations of the Kv1.1 gene from the Shaker K+ channel subfamily. To study the functional effects of the disease-causing mutations in a robust K+ channel background, we introduced seven different episodic ataxia type 1 substitutions into the corresponding, conserved residues of the Shaker K+ channel. K+ channel currents expressed in Xenopus oocytes were studied by electrophysiology. All episodic ataxia type 1 mutations produced functional K+ channels. In a Shaker N-terminal deletion mutant with fast inactivation removed, current amplitudes were significantly reduced in channels harboring an episodic ataxia type 1 mutation. Six of the seven mutations also showed depolarizing shifts (+9 to +36 mV) in the conductance voltage dependence. One mutation (F307I) shifted the midpoint of the conductance-voltage relationship by 23 mV in the hyperpolarizing direction. Episodic ataxia type 1 mutations were also expressed in ShakerH4 with intact N-terminal inactivation. In this construct, current amplitudes for episodic ataxia type 1 mutants were not significantly different from wild-type channels. All mutations altered the voltage range of steady-state inactivation; most changes were coupled to the changes in activation gating. Some episodic ataxia type 1 mutants also caused significant changes in the kinetics of N-type (F307I, E395D) or C-type (F307I, E395D, V478A) inactivation. These results suggest that episodic ataxia type 1 mutations may change K+ channel function by two mechanisms: (i) reduced channel expression and (ii) altered channel gating.


Subject(s)
Ataxia/genetics , Fasciculation/genetics , Mutation/physiology , Potassium Channels/genetics , Animals , Ataxia/physiopathology , Drosophila , Drosophila Proteins , Female , Ion Channel Gating/physiology , Oocytes/metabolism , Patch-Clamp Techniques , Shaker Superfamily of Potassium Channels , Xenopus laevis
16.
Bone Marrow Transplant ; 18(4): 705-12, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8899184

ABSTRACT

We have quantitated colony-forming unit megakaryocyte, (CFU-Mk), burst-forming unit megakaryocyte, (BFU-Mk), colony-forming unit granulocyte-macrophage (CFU-GM), and CD34+ cells in 98 mobilised PB samples from 53 patients mobilised by one of six protocols, including myelosuppressive chemotherapy alone (n = 22), or in combination with recombinant haemopoietic growth factors (n = 32), and growth factors alone (n = 17) or in combination (n = 27). The frequency of megakaryocyte progenitors (total Mk = CFU-Mk + BFU-Mk) in mobilised PB (mean 356, range 0-3240/10(6)) was similar to that in steady-state BM (mean 429, range 0-3315/10(6) n = 45). The levels of total Mk in mobilised PB (mean 1509, range 0-36 099/ml) showed a mean 75-fold increase compared with steady state PB (mean 20, range 0-86/ml, n = 15). In mobilised PB the levels of CFU-Mk were significantly correlated with levels of BFU-Mk (rs = 0.71, P < 0.0001) and the levels of megakaryocyte progenitors correlated significantly with those of myeloid progenitors (rs = 0.59, P < 0.0001) and CD34+ cells (rs = 0.69, P < 0.0001). The mobilisation of megakaryocyte progenitors into the circulation in response to high-dose chemotherapy and/or haemopoietic growth factors contributes to an understanding of the rapid platelet recovery following PBSC transplantation and suggests that the measurement of megakaryocyte progenitors may be a useful indicator for platelet reconstitutive capacity.


Subject(s)
Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells/drug effects , Megakaryocytes/drug effects , Adult , Antineoplastic Agents, Alkylating/administration & dosage , Blood Cell Count , Clinical Protocols , Colony-Forming Units Assay , Cyclophosphamide/administration & dosage , Female , Hematopoietic Cell Growth Factors/administration & dosage , Hematopoietic Stem Cells/cytology , Humans , Male , Megakaryocytes/cytology , Neoplasms/blood , Neoplasms/therapy , Platelet Count
17.
Ann N Y Acad Sci ; 938: 208-18; discussion 218-20, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11458510

ABSTRACT

Recent discoveries have demonstrated the extraordinary plasticity of tissue-derived stem cells, raising fundamental questions about cell lineage relationships and suggesting the potential for novel cell-based therapies. We have examined this phenomenon in a potential reciprocal relationship between stem cells derived from the skeletal muscle and from the bone marrow. We have discovered that cells derived from the skeletal muscle of adult mice contain a remarkable capacity for hematopoietic differentiation. Cells prepared from muscle by enzymatic digestion and 5 day in vitro culture were harvested and introduced into each of six lethally irradiated recipients together with distinguishable whole bone marrow cells. Six and twelve weeks later, all recipients showed high-level engraftment of muscle-derived cells representing all major adult blood lineages. The mean total contribution of muscle cell progeny to peripheral blood was 56%, indicating that the cultured muscle cells generated approximately 10- to 14-fold more hematopoietic activity than whole bone marrow. Although the identity of the muscle-derived hematopoietic stem cells is still unknown, they may be identical to muscle satellite cells, some of which lack myogenic regulators and could respond to hematopoietic signals. We have also found that stem cells in the bone marrow can contribute to cardiac muscle repair and neovascularization after ischemic injury. We transplanted highly purified bone marrow stem cells into lethally irradiated mice that subsequently were rendered ischemic by coronary artery occlusion and reperfusion. The engrafted stem cells or their progeny differentiated into cardiomyocytes and endothelial cells and contributed to the formation of functional tissue.


Subject(s)
Bone Marrow Cells/cytology , Hematopoiesis/physiology , Muscle, Skeletal/cytology , Stem Cells/cytology , Age Factors , Animals , Bone Marrow Transplantation , Cell Differentiation , Cell Lineage , Cell Transplantation , Cells, Cultured/transplantation , Graft Survival , Hematopoietic Stem Cells/cytology , Humans , Mice , Mice, Inbred C57BL , Muscle Development , Muscle, Skeletal/growth & development , Myocardial Ischemia/therapy , Myocardial Reperfusion Injury/therapy , Myocardium/pathology , Neovascularization, Physiologic , Organ Specificity , Radiation Chimera , Stem Cell Transplantation
18.
Science ; 152(3721): 545-6, 1966 Apr 22.
Article in English | MEDLINE | ID: mdl-17815085
19.
Vet Immunol Immunopathol ; 73(3-4): 323-9, 2000 Mar 15.
Article in English | MEDLINE | ID: mdl-10713344

ABSTRACT

Expression of the low-affinity IgE receptor (CD23) on the surface of mononuclear cells is a critical event in the development of IgE-mediated immunologic responses. Using PCR and cDNA library screening, a 2.7kb cDNA encoding equine CD23 and a 627bp PCR fragment of cattle CD23 were sequenced and characterized. The equine CD23 sequence encodes a complete and continuous open reading frame of 327 amino acids, while the shorter cattle fragment encodes 209 amino acids corresponding to nucleotides 325-1098 of the equine CD23 transcript. In addition to high identities in their nucleotides and translated amino acids with CD23 sequences published for other species, the translated equine CD23 protein also shares many of the structural features of this molecule described for human and rodents. Interestingly, an additional repetitive element of possible functional significance consisting of 18 amino acids, located between the transmembrane region and the carbohydrate-binding lectin domain of horse CD23, was also identified. Based on these sequences, molecular assays will be developed to measure CD23 mRNA in tissues and expression of recombinant proteins will be essential to the production of species-specific antibody reagents. These assays and reagents will be useful in future studies of allergic and lymphoproliferative diseases in horses and cattle.


Subject(s)
Cattle/genetics , Horses/genetics , Receptors, IgE/genetics , Amino Acid Sequence , Animals , Base Sequence , Cloning, Molecular , DNA, Complementary/analysis , Molecular Sequence Data , Polymerase Chain Reaction/veterinary , Sequence Analysis, DNA , Sequence Homology, Amino Acid
20.
Vet Immunol Immunopathol ; 97(3-4): 187-94, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14741137

ABSTRACT

Three overlapping fragments of the equine interleukin-4 receptor alpha chain gene (IL4R) were cloned and sequenced. The resulting 3553 bp cDNA sequence exhibited homology to human, murine and bovine IL4R. The equine IL4R exhibits many conserved features when compared to other species, including intron-exon boundary positions and amino acid sequence motifs characteristic of type I cytokine receptors. The IL4R gene was localized to horse chromosome ECA13 by synteny mapping on a somatic cell hybrid panel. Evidence for an alternative splice variant of IL4R was found in the genomic sequence and subsequently verified using RT-PCR on equine monocyte RNA. A polymorphism screen of the largest exon, homologous to exon 12 of the human IL4R gene, was performed using DNA from 60 horses of various breeds which yielded 11 coding-region single nucleotide polymorphisms (SNPs), 7 synonymous and 4 non-synonymous. Three of the four non-synonymous SNPs occur at high frequencies and are found very near a conserved tyrosine residue.


Subject(s)
Horse Diseases/genetics , Horse Diseases/immunology , Horses/genetics , Receptors, Interleukin-4/genetics , Alternative Splicing , Amino Acid Sequence , Animals , Base Sequence , Chromosome Mapping/veterinary , Cloning, Molecular , DNA, Complementary/genetics , Humans , Molecular Sequence Data , Polymorphism, Single Nucleotide , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Receptors, Interleukin-4/immunology , Reverse Transcriptase Polymerase Chain Reaction/veterinary , Sequence Alignment , Sequence Analysis, DNA
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