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1. Persistent bacteremia predicts poor outcomes among neutropenic patients with carbapenem-resistant gram-negative bloodstream infections receiving appropriate therapy

Author

Sathya Kumar, Abi Manesh, George, Mithun Mohan, Bhanuprasad, Kundakarla, John, Grace Mary, Korula, Anu, Abraham, Aby, Mathews, Vikram, Kulkarni, Uday Prakash, Shankar, Chaitra, Premkumar, Prasanna Samuel, Chacko, Binila, Subramani, K., Varghese, George M., Balaji, V., and George, Biju

Published
2023
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3. A stomatal safety-efficiency trade-off constrains responses to leaf dehydration.

Author

Henry, Christian, John, Grace P, Pan, Ruihua, Bartlett, Megan K, Fletcher, Leila R, Scoffoni, Christine, and Sack, Lawren

Subjects
Plant Leaves, Water, Environment, Ecosystem, California, Plant Stomata, Droughts
Abstract

Stomata, the microvalves on leaf surfaces, exert major influences across scales, from plant growth and productivity to global carbon and water cycling. Stomatal opening enables leaf photosynthesis, and plant growth and water use, whereas plant survival of drought depends on stomatal closure. Here we report that stomatal function is constrained by a safety-efficiency trade-off, such that species with greater stomatal conductance under high water availability (gmax) show greater sensitivity to closure during leaf dehydration, i.e., a higher leaf water potential at which stomatal conductance is reduced by 50% (Ψgs50). The gmax - Ψgs50 trade-off and its mechanistic basis is supported by experiments on leaves of California woody species, and in analyses of previous studies of the responses of diverse flowering plant species around the world. Linking the two fundamental key roles of stomata-the enabling of gas exchange, and the first defense against drought-this trade-off constrains the rates of water use and the drought sensitivity of leaves, with potential impacts on ecosystems.

Published
2019

4. ABA Accumulation in Dehydrating Leaves Is Associated with Decline in Cell Volume, Not Turgor Pressure

Author

Sack, Lawren, John, Grace P, and Buckley, Thomas N

Subjects
Abscisic Acid, Cell Size, Dehydration, Models, Biological, Plant Leaves, Pressure, Water, Biological Sciences, Agricultural and Veterinary Sciences, Plant Biology & Botany
Abstract

Reanalysis of published experimental data shows that in dehydrating leaves ABA accumulation is linked with reduction of cell volume rather than turgor, providing clues toward signaling mechanisms.

Published
2018

5. The anatomical and compositional basis of leaf mass per area

Author

John, Grace P, Scoffoni, Christine, Buckley, Thomas N, Villar, Rafael, Poorter, Hendrik, and Sack, Lawren

Subjects
Plant Biology, Biological Sciences, Ecology, Life History Traits, Magnoliopsida, Models, Biological, Plant Leaves, Deciduous, evergreen, functional traits, leaf anatomy, leaf density, leaf economics, leaf thickness, mesophyll, SLA, specific leaf area, SLA, Ecological Applications, Evolutionary Biology, Ecological applications, Environmental management
Abstract

Leaf dry mass per unit leaf area (LMA) is a central trait in ecology, but its anatomical and compositional basis has been unclear. An explicit mathematical and physical framework for quantifying the cell and tissue determinants of LMA will enable tests of their influence on species, communities and ecosystems. We present an approach to explaining LMA from the numbers, dimensions and mass densities of leaf cells and tissues, which provided unprecedented explanatory power for 11 broadleaved woody angiosperm species diverse in LMA (33-262 g m-2 ; R2  = 0.94; P

Published
2017

6. The Sites of Evaporation within Leaves

Author

Buckley, Thomas N, John, Grace P, Scoffoni, Christine, and Sack, Lawren

Subjects
Algorithms, Biological Transport, Computer Simulation, Humidity, Light, Mesophyll Cells, Models, Biological, Plant Epidermis, Plant Leaves, Plant Stomata, Plant Transpiration, Plants, Species Specificity, Temperature, Water, Xylem, Biological Sciences, Agricultural and Veterinary Sciences, Plant Biology & Botany
Abstract

The sites of evaporation within leaves are unknown, but they have drawn attention for decades due to their perceived implications for many factors, including patterns of leaf isotopic enrichment, the maintenance of mesophyll water status, stomatal regulation, and the interpretation of measured stomatal and leaf hydraulic conductances. We used a spatially explicit model of coupled water and heat transport outside the xylem, MOFLO 2.0, to map the distribution of net evaporation across leaf tissues in relation to anatomy and environmental parameters. Our results corroborate earlier predictions that most evaporation occurs from the epidermis at low light and moderate humidity but that the mesophyll contributes substantially when the leaf center is warmed by light absorption, and more so under high humidity. We also found that the bundle sheath provides a significant minority of evaporation (15% in darkness and 18% in high light), that the vertical center of amphistomatous leaves supports net condensation, and that vertical temperature gradients caused by light absorption vary over 10-fold across species, reaching 0.3°C. We show that several hypotheses that depend on the evaporating sites require revision in light of our findings, including that experimental measurements of stomatal and hydraulic conductances should be affected directly by changes in the location of the evaporating sites. We propose a new conceptual model that accounts for mixed-phase water transport outside the xylem. These conclusions have far-reaching implications for inferences in leaf hydraulics, gas exchange, water use, and isotope physiology.

Published
2017

8. Leaf vein xylem conduit diameter influences susceptibility to embolism and hydraulic decline.

Author

Scoffoni, Christine, Albuquerque, Caetano, Brodersen, Craig R, Townes, Shatara V, John, Grace P, Cochard, Hervé, Buckley, Thomas N, McElrone, Andrew J, and Sack, Lawren

Subjects
Plant Leaves, Dehydration, Water, Imaging, Three-Dimensional, Species Specificity, Models, Biological, Computer Simulation, Xylem, X-Ray Microtomography, cavitation, microCT, percentage loss of conductivity, venation architecture, xylem collapse, Imaging, Three-Dimensional, Models, Biological, Biological Sciences, Agricultural And Veterinary Sciences, Plant Biology & Botany, Agricultural and Veterinary Sciences
Abstract

Ecosystems worldwide are facing increasingly severe and prolonged droughts during which hydraulic failure from drought-induced embolism can lead to organ or whole plant death. Understanding the determinants of xylem failure across species is especially critical in leaves, the engines of plant growth. If the vulnerability segmentation hypothesis holds within leaves, higher order veins that are most terminal in the plant hydraulic system should be more susceptible to embolism to protect the rest of the water transport system. Increased vulnerability in the higher order veins would also be consistent with these experiencing the greatest tensions in the plant xylem network. To test this hypothesis, we combined X-ray micro-computed tomography imaging, hydraulic experiments, cross-sectional anatomy and 3D physiological modelling to investigate how embolisms spread throughout petioles and vein orders during leaf dehydration in relation to conduit dimensions. Decline of leaf xylem hydraulic conductance (Kx ) during dehydration was driven by embolism initiating in petioles and midribs across all species, and Kx vulnerability was strongly correlated with petiole and midrib conduit dimensions. Our simulations showed no significant impact of conduit collapse on Kx decline. We found xylem conduit dimensions play a major role in determining the susceptibility of the leaf water transport system during strong leaf dehydration.

Published
2017

11. Allometries of cell and tissue anatomy and photosynthetic rate across leaves of C 3 and C 4 grasses

Author

Baird, Alec S., Taylor, Samuel H., Reddi, Sachin, Pasquet‐Kok, Jessica, Vuong, Christine, Zhang, Yu, Watcharamongkol, Teera, John, Grace P., Scoffoni, Christine, Osborne, Colin P., Sack, Lawren, Baird, Alec S., Taylor, Samuel H., Reddi, Sachin, Pasquet‐Kok, Jessica, Vuong, Christine, Zhang, Yu, Watcharamongkol, Teera, John, Grace P., Scoffoni, Christine, Osborne, Colin P., and Sack, Lawren

Abstract

Allometric relationships among the dimensions of leaves and their cells hold across diverse eudicotyledons, but have remained untested in the leaves of grasses. We hypothesised that geometric (proportional) allometries of cell sizes across tissues and of leaf dimensions would arise due to the coordination of cell development and that of cell functions such as water, nutrient and energy transport, and that cell sizes across tissues would be associated with light‐saturated photosynthetic rate. We tested predictions across 27 globally distributed C3 and C4 grass species grown in a common garden. We found positive relationships among average cell sizes within and across tissues, and of cell sizes with leaf dimensions. Grass leaf anatomical allometries were similar to those of eudicots, with exceptions consistent with the fewer cell layers and narrower form of grass leaves, and the specialised roles of epidermis and bundle sheath in storage and leaf movement. Across species, mean cell sizes in each tissue were associated with light‐saturated photosynthetic rate per leaf mass, supporting the functional coordination of cell sizes. These findings highlight the generality of evolutionary allometries within the grass lineage and their interlinkage with coordinated development and function.

Published
2024

12. Leaf mass per area is independent of vein length per area: avoiding pitfalls when modelling phenotypic integration (reply to )

Author

Sack, Lawren, Scoffoni, Christine, John, Grace P, Poorter, Hendrik, Mason, Chase M, Mendez-Alonzo, Rodrigo, and Donovan, Lisa A

Subjects
Photosynthesis, Plant Transpiration, Plant Vascular Bundle, Plants, Functional traits, leaf hydraulics, leaf mass per area, leaf nutrient concentrations, photosynthetic rate, vasculature, vein patterning, vein patterning., Genetics, Plant Biology, Crop and Pasture Production, Plant Biology & Botany
Abstract

It has been recently proposed that leaf vein length per area (VLA) is the major determinant of leaf mass per area ( MA), and would thereby determine other traits of the leaf economic spectrum (LES), such as photosynthetic rate per mass (A(mass)), nitrogen concentration per mass (N(mass)) and leaf lifespan (LL). In a previous paper we argued that this 'vein origin' hypothesis was supported only by a mathematical model with predestined outcomes, and that we found no support for the 'vein origin' hypothesis in our analyses of compiled data. In contrast to the 'vein origin' hypothesis, empirical evidence indicated that VLA and LMA are independent mechanistically, and VLA (among other vein traits) contributes to a higher photosynthetic rate per area (A(area)), which scales up to driving a higher A(mass), all independently of LMA, N(mass) and LL. In their reply to our paper, Blonder et al. (2014) raised questions about our analysis of their model, but did not address our main point, that the data did not support their hypothesis. In this paper we provide further analysis of an extended data set, which again robustly demonstrates the mechanistic independence of LMA from VLA, and thus does not support the 'vein origin' hypothesis. We also address the four specific points raised by Blonder et al. (2014) regarding our analyses. We additionally show how this debate provides critical guidance for improved modelling of LES traits and other networks of phenotypic traits that determine plant performance under contrasting environments.

Published
2014

13. Embracing 3D Complexity in Leaf Carbon–Water Exchange

Author

Earles, J. Mason, Buckley, Thomas N., Brodersen, Craig R., Busch, Florian A., Cano, F. Javier, Choat, Brendan, Evans, John R., Farquhar, Graham D., Harwood, Richard, Huynh, Minh, John, Grace P., Miller, Megan L., Rockwell, Fulton E., Sack, Lawren, Scoffoni, Christine, Struik, Paul C., Wu, Alex, Yin, Xinyou, and Barbour, Margaret M.

Published
2019
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17. Predicting plant species climate niches on the basis of mechanistic traits

Author

Medeiros, Camila D., primary, Henry, Christian, additional, Trueba, Santiago, additional, Anghel, Ioana, additional, Guerrero, Samantha Dannet Diaz de Leon, additional, Pivovaroff, Alexandria, additional, Fletcher, Leila R., additional, John, Grace P., additional, Lutz, James A., additional, Méndez Alonzo, Rodrigo, additional, and Sack, Lawren, additional

Published
2023
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18. Spectral ecophysiology: hyperspectral pressure–volume curves to estimate leaf turgor loss.

Author

Castillo‐Argaez, Raiza, Sapes, Gerard, Mallen, Nicole, Lippert, Alston, John, Grace P., Zare, Alina, and Hammond, William M.

Subjects
ECOPHYSIOLOGY, TURGOR, SPECTRAL reflectance, DROUGHT tolerance, PLANT mortality, PLANT-water relationships, LEAF physiology
Abstract

Summary: Turgor loss point (TLP) is an important proxy for plant drought tolerance, species habitat suitability, and drought‐induced plant mortality risk. Thus, TLP serves as a critical tool for evaluating climate change impacts on plants, making it imperative to develop high‐throughput and in situ methods to measure TLP.We developed hyperspectral pressure–volume curves (PV curves) to estimate TLP using leaf spectral reflectance. We used partial least square regression models to estimate water potential (Ψ) and relative water content (RWC) for two species, Frangula caroliniana and Magnolia grandiflora. RWC and Ψ's model for each species had R2 ≥ 0.7 and %RMSE = 7–10. We constructed PV curves with model estimates and compared the accuracy of directly measured and spectra‐predicted TLP.Our findings indicate that leaf spectral measurements are an alternative method for estimating TLP. F. caroliniana TLP's values were −1.62 ± 0.15 (means ± SD) and −1.62 ± 0.34 MPa for observed and reflectance predicted, respectively (P > 0.05), while M. grandiflora were −1.78 ± 0.34 and −1.66 ± 0.41 MPa (P > 0.05).The estimation of TLP through leaf reflectance‐based PV curves opens a broad range of possibilities for future research aimed at understanding and monitoring plant water relations on a large scale with spectral ecophysiology. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Allometries of cell and tissue anatomy and photosynthetic rate across leaves of C3 and C4 grasses.

Author

Baird, Alec S., Taylor, Samuel H., Reddi, Sachin, Pasquet‐Kok, Jessica, Vuong, Christine, Zhang, Yu, Watcharamongkol, Teera, John, Grace P., Scoffoni, Christine, Osborne, Colin P., and Sack, Lawren

Subjects
CELL anatomy, PHOTOSYNTHETIC rates, CELL size, ALLOMETRY, GRASSES, CELL physiology, EPIDERMIS
Abstract

Allometric relationships among the dimensions of leaves and their cells hold across diverse eudicotyledons, but have remained untested in the leaves of grasses. We hypothesised that geometric (proportional) allometries of cell sizes across tissues and of leaf dimensions would arise due to the coordination of cell development and that of cell functions such as water, nutrient and energy transport, and that cell sizes across tissues would be associated with light‐saturated photosynthetic rate. We tested predictions across 27 globally distributed C3 and C4 grass species grown in a common garden. We found positive relationships among average cell sizes within and across tissues, and of cell sizes with leaf dimensions. Grass leaf anatomical allometries were similar to those of eudicots, with exceptions consistent with the fewer cell layers and narrower form of grass leaves, and the specialised roles of epidermis and bundle sheath in storage and leaf movement. Across species, mean cell sizes in each tissue were associated with light‐saturated photosynthetic rate per leaf mass, supporting the functional coordination of cell sizes. These findings highlight the generality of evolutionary allometries within the grass lineage and their interlinkage with coordinated development and function. Summary statement: Allometries among leaf cell sizes and of cell sizes with leaf dimensions and photosynthetic rate hold across grass species, supporting their basis in developmental and functional coordination. [ABSTRACT FROM AUTHOR]

Published
2024
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27. The structural and compositional basis of leaf traits and their influence on plant water use and drought tolerance

Author

John, Grace Patricia

Subjects
Plant sciences, Physiology, Ecology, drought tolerance, leaf anatomy, plant physiology, scaling, urban trees, water use
Abstract

Plants provide invaluable ecosystem services to urban centers. Yet, these services cannot be decoupled from the cost to maintain landscaping plants. Costs are particularly difficult to quantify in urban ecosystems, like Los Angeles, where a combination of mild climate and a legacy of landscape design driven by social and economic factors has produced unprecedented species diversity. As these plants subsist entirely on irrigation water, the resulting ‘global common garden’ is ideally suited for testing anatomical and physiological scaling hypotheses across many diverse species to inform generalized predictive models for other species and ecosystems. My dissertation seeks to uncover relationships between leaf anatomy and function to build models estimating water use and drought tolerance in Los Angeles.I first analyzed allometric slopes describing relationships between the dimensions of leaf cells and tissues and found cell sizes, cell wall thickness and leaf thickness scale together across tissues and species. I then created a mathematically explicit model that predicted leaf mass per area (LMA) from its constitutive anatomy and composition with unprecedented explanatory power. Cell size, the number of mesophyll cell layers, and cell mass density principally drove species differences in LMA and had strong impacts on the Leaf Economics Spectrum. I linked leaf structure with physiology by resurrecting a classic method for quantifying loss of rehydration capacity in dehydrating leaves, placed associated thresholds in the sequence of drought response (e.g. stomatal closure, turgor loss), and tested their relationship with structure and composition. I found leaves to be considerably more vulnerable than previously believed. This prompted a study in which I tested canopy stomatal conductance across minor shifts in vapor pressure deficit (VPD) modeled from plant traits against empirical sap flux and leaf area data collected in urban trees. Finally, I found enormous variation in functional traits across Los Angeles species, influenced by climates of origin, growth forms, leaf habit and canopy position (i.e., sun versus shade leaves). The vast trait diversity in Los Angeles urban trees demonstrates the need for integration of species information into predictive models in urban ecosystems and highlights Los Angeles as an invaluable resource for future ecophysiological study.

Published
2017

28. Impact of Percutaneous Coronary Intervention in the Right Coronary Artery on Right Ventricular Function in Patients with Acute Myocardial Infarction.

Author

Kiran, Ganthala Paul, Santosh, T., John, Grace Madhuri, and Rao, M. Srinivasa

Subjects
ECHOCARDIOGRAPHY, LEFT heart ventricle, PERCUTANEOUS coronary intervention, CLINICAL trials, VENTRICULAR ejection fraction, RIGHT heart ventricle, RESEARCH methodology, MYOCARDIAL infarction, TERTIARY care, CARDIAC contraction, TRICUSPID valve, TREATMENT effectiveness, PRE-tests & post-tests, COMPARATIVE studies, MYOCARDIAL revascularization, DESCRIPTIVE statistics, RIGHT ventricular dysfunction, CORONARY arteries, HEART physiology, DATA analysis, DATA analysis software, DIASTOLE (Cardiac cycle), ACUTE diseases, LONGITUDINAL method
Abstract

Background: Right ventricular (RV) dysfunction is a potent predictor of mortality and morbidity after acute myocardial infarction (MI). Even though elective percutaneous coronary intervention (PCI) has significantly decreased myocardial damage of the left ventricle; in literature, there has been a lack of information regarding the effect of PCI on RV function. Objective: The objective of this study is to examine the effect of the right coronary artery (RCA) revascularization on systolic and diastolic functions of the right ventricle following acute inferior wall MI (IWMI). Subjects and Methods: Fifty-nine patients diagnosed with acute IWMI following RCA revascularization were prospectively investigated between April 2018 and January 2020. Patients were subjected to two-dimensional echocardiography. RV systolic and diastolic functions were reported before and after the PCI procedure and compared using different echocardiographic RV systolic and diastolic parameters. Results: After PCI, echocardiographic RV systolic and diastolic functions were significantly improved in proximal and mid RCA in terms of tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RVFAC), and early RV filling velocity/late RV filling velocity (E/A). Significant improvement was found in mid RCA in terms of peak systolic (S') velocity (P = 0.008) and proximal RCA in terms of early RV filling velocity/early diastolic tricuspid annulus velocity (E/e') (P = 0.021). Overall echocardiographic systolic and diastolic parameters in patients with RV dysfunction following PCI were improved (TAPSE [37.29% vs. 81.82%], S' velocity [37.29% vs. 68.18%], RVFAC [33.90% vs. 90.00%], and E/A [33.90% vs. 75.00%]). Conclusions: Patients with RV dysfunction were remarkably improved after RCA revascularization. Hence, RCA revascularization can become an appropriate treatment alternative for the recovery of patients who suffer from RV dysfunction. [ABSTRACT FROM AUTHOR]

Published
2023
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30. Embracing 3D Complexity in Leaf Carbon-Water Exchange

Author

Earles, Jeffrey Mason, Buckley, Thomas N., Brodersen, Craig R., Busch, Florian, Cano, Francisco Javier, Choat, Brendan, Evans, John R., Farquhar, Graham, Harwood, Richard, Huynh, Minh, John, Grace P., Miller, Megan L., Rockwell, F. E., Earles, Jeffrey Mason, Buckley, Thomas N., Brodersen, Craig R., Busch, Florian, Cano, Francisco Javier, Choat, Brendan, Evans, John R., Farquhar, Graham, Harwood, Richard, Huynh, Minh, John, Grace P., Miller, Megan L., and Rockwell, F. E.

Abstract

Leaves are a nexus for the exchange of water, carbon, and energy between terrestrial plants and the atmosphere. Research in recent decades has highlighted the critical importance of the underlying biophysical and anatomical determinants of CO2 and H2O transport, but a quantitative understanding of how detailed 3D leaf anatomy mediates within-leaf transport has been hindered by the lack of a consensus framework for analyzing or simulating transport and its spatial and temporal dynamics realistically, and by the difficulty of measuring within-leaf transport at the appropriate scales. We discuss how recent technological advancements now make a spatially explicit 3D leaf analysis possible, through new imaging and modeling tools that will allow us to address long-standing questions related to plant carbon–water exchange.

Published
2019

33. Outside-Xylem Vulnerability, Not Xylem Embolism, Controls Leaf Hydraulic Decline during Dehydration1[CC-BY]

Author

Scoffoni, Christine, Albuquerque, Caetano, Brodersen, Craig R., Townes, Shatara V., John, Grace P., Bartlett, Megan K., Buckley, Thomas N., McElrone, Andrew J., and Sack, Lawren

Subjects
Dehydration, fungi, food and beverages, Water, Biological Transport, Articles, X-Ray Microtomography, Models, Biological, Droughts, Plant Leaves, Magnoliopsida, Species Specificity, Xylem, Computer Simulation, sense organs, skin and connective tissue diseases
Abstract

Changes in leaf outside-xylem properties drive leaf and whole-plant hydraulic decline with dehydration, protecting plants from catastrophic embolism in xylem conduits.

Published
2017

36. Leaf mass per area is independent of vein length per area: avoiding pitfalls when modelling phenotypic integration (reply to Blonder et al. 2014).

Author

Sack, Lawren, Sack, Lawren, Scoffoni, Christine, John, Grace P, Poorter, Hendrik, Mason, Chase M, Mendez-Alonzo, Rodrigo, Donovan, Lisa A, Sack, Lawren, Sack, Lawren, Scoffoni, Christine, John, Grace P, Poorter, Hendrik, Mason, Chase M, Mendez-Alonzo, Rodrigo, and Donovan, Lisa A

Abstract

It has been recently proposed that leaf vein length per area (VLA) is the major determinant of leaf mass per area ( MA), and would thereby determine other traits of the leaf economic spectrum (LES), such as photosynthetic rate per mass (A(mass)), nitrogen concentration per mass (N(mass)) and leaf lifespan (LL). In a previous paper we argued that this 'vein origin' hypothesis was supported only by a mathematical model with predestined outcomes, and that we found no support for the 'vein origin' hypothesis in our analyses of compiled data. In contrast to the 'vein origin' hypothesis, empirical evidence indicated that VLA and LMA are independent mechanistically, and VLA (among other vein traits) contributes to a higher photosynthetic rate per area (A(area)), which scales up to driving a higher A(mass), all independently of LMA, N(mass) and LL. In their reply to our paper, Blonder et al. (2014) raised questions about our analysis of their model, but did not address our main point, that the data did not support their hypothesis. In this paper we provide further analysis of an extended data set, which again robustly demonstrates the mechanistic independence of LMA from VLA, and thus does not support the 'vein origin' hypothesis. We also address the four specific points raised by Blonder et al. (2014) regarding our analyses. We additionally show how this debate provides critical guidance for improved modelling of LES traits and other networks of phenotypic traits that determine plant performance under contrasting environments.

Published
2014

38. Effect of breastfeeding on mortality among HIV-1 infected women: a randomised trial

Author

Nduati, Ruth, Richardson, Barbra A, John, Grace, Mbori-Ngacha, Dorothy, Mwatha, Anthony, Ndinya-Achola, Jeckoniah, Bwayo, Job, Onyango, Francis E, and Kreiss, Joan

Abstract

We have completed a randomised clinical trial of breastfeeding and formula feeding to identify the frequency of breastmilk transmission of HIV-1 to infants. However, we also analysed data from this trial to examine the effect of breastfeeding on maternal death rates during 2 years after delivery. We report our findings from this secondary analysis.

Published
2001
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39. Maternal SDF1 3'A Polymorphism Is Associated with Increased Perinatal Human Immunodeficiency Virus Type 1 Transmission

Author

John, Grace C., Rousseau, Christine, Dong, Tao, Rowland-Jones, Sarah, Nduati, Ruth, Mbori-Ngacha, Dorothy, Rostron, Tim, Kreiss, Joan K., Richardson, Barbra A., and Overbaugh, Julie

Abstract

ABSTRACTGenetic polymorphisms in chemokine and chemokine receptor genes influence susceptibility to human immunodeficiency virus type 1 (HIV-1) infection and disease progression, but little is known regarding the association between these allelic variations and the ability of the host to transmit virus. In this study, we show that the maternal heterozygous SDF1 genotype (SDF1 3'A/wt) is associated with perinatal transmission of HIV-1 (risk ratio [RR], 1.8; 95% confidence interval [CI], 1.0 to 3.3) and particularly postnatal breastmilk transmission (RR, 3.1; 95% CI, 1.1 to 8.6). In contrast, the infant SDF1 genotype had no effect on mother-to-infant transmission. These data suggest that SDF1, which is a ligand for the T-tropic HIV-1 coreceptor CXCR4, may affect the ability of a mother to transmit the virus to her infant. This suggests that a genetic polymorphism in a gene encoding a chemokine receptor ligand may be associated with increased infectivity of the index case and highlights the importance of considering transmission as well as clinical outcome in designing chemokine-based therapies for HIV-1.

Published
2000
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40. Subtypes of Human Immunodeficiency Virus Type 1 and Disease Stage among Women in Nairobi, Kenya

Author

Neilson, Joel R., John, Grace C., Carr, Jean K., Lewis, Paul, Kreiss, Joan K., Jackson, Stephanie, Nduati, Ruth W., Mbori-Ngacha, Dorothy, Panteleeff, Dana D., Bodrug, Sharon, Giachetti, Christina, Bott, Martha A., Richardson, Barbra A., Bwayo, Job, Ndinya-Achola, Jeckoniah, and Overbaugh, Julie

Abstract

ABSTRACTIn sub-Saharan Africa, where the effects of human immunodeficiency virus type 1 (HIV-1) have been most devastating, there are multiple subtypes of this virus. The distribution of different subtypes within African populations is generally not linked to particular risk behaviors. Thus, Africa is an ideal setting in which to examine the diversity and mixing of viruses from different subtypes on a population basis. In this setting, it is also possible to address whether infection with a particular subtype is associated with differences in disease stage. To address these questions, we analyzed the HIV-1 subtype, plasma viral loads, and CD4 lymphocyte levels in 320 women from Nairobi, Kenya. Subtype was determined by a combination of heteroduplex mobility assays and sequence analyses of envelope genes, using geographically diverse subtype reference sequences as well as envelope sequences of known subtype from Kenya. The distribution of subtypes in this population was as follows: subtype A, 225 (70.3%); subtype D, 65 (20.5%); subtype C, 22 (6.9%); and subtype G, 1 (0.3%). Intersubtype recombinant envelope genes were detected in 2.2% of the sequences analyzed. Given that the sequences analyzed represented only a small fraction of the proviral genome, this suggests that intersubtype recombinant viral genomes may be very common in Kenya and in other parts of Africa where there are multiple subtypes. The plasma viral RNA levels were highest in women infected with subtype C virus, and women infected with subtype C virus had significantly lower CD4 lymphocyte levels than women infected with the other subtypes. Together, these data suggest that women in Kenya who are infected with subtype C viruses are at more advanced stages of immunosuppression than women infected with subtype A or D. There are at least two models to explain the data from this cross-sectional study; one is that infection with subtype C is associated with a more rapid disease progression, and the second is that subtype C represents an older epidemic in Kenya. Discriminating between these possibilities in a longitudinal study will be important for increasing our understanding of the role of specific subtypes in the transmission and pathogenesis of HIV-1.

Published
1999
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41. Five-Year Knowledge Retention by Volunteer Primary Health Workers in Western Nigeria

Author

Ryan, Julie M., John, Grace C., and Brieger, William R.

Abstract

A volunteer primary health worker (PHW) must acquire a basic knowledge of preventive and curative medicine to approach his community with authority. Knowledge gained during training must be retained as a foundation for village level action. This study is a follow-up survey of knowledge among PHWs in a Western Nigerian town five years after training. The same end of course test was administered and results compared with age, sex, level of education and level of activity in PHC programming. The follow-up test scores showed an expected decrease in information retained. The only demographic factor consistently associated with knowledge after training and at follow-up was level of education. In addition level of PHC activity (e.g., attending PHW meetings, maintaining a village drug box) was associated with greater knowledge, but was also positively related to level of education. It is therefore recommended that PHC programs ideally recruit PHWs with vernacular literacy, but where this is not possible, extra effort must be put into close follow-up supervision of trainees.

Published
1990
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42. Cesarean delivery in women with genital herpes in Washington state, 1989–1991

Author

Marrazzo, Jeanne M., John, Grace C., and Krohn, Marijane A.

Abstract

The purpose of this study was to determine whether the proportion of cesarean deliveries in pregnant women with a history of genital herpes and no active lesions at birth is higher than that in women with no history of genital herpes, and to determine whether this risk was modified by birth facilities' underlying prevalence of cesarean delivery. This was a retrospective survey. Women who gave birth in Washington state from 1989 to 1991 were identified from the state birth records and were classified as having clinical genital herpes during pregnancy (N = 1,094) or history of genital herpes only (N = 4,163) at delivery. Women without genital herpes (N = 5,257) were randomly selected from remaining births. The main outcome measure was primary cesarean delivery, excluding those performed for indications other than genital herpes. Prevalence of primary cesarean delivery was 59.5% in women with clinical herpes during pregnancy and 12.5% in women with history of herpes, both significantly different from prevalence of 11.2% in unexposed women. Age-adjusted risk for cesarean delivery among women with a history of herpes was 1.13 [95% confidence interval (CI): 0.93, 1.37]. When baseline cesarean delivery prevalence was above 20%, this risk was 1.2 (95% CI: 1.0, 1.4; P = 0.058), compared to 1.1 (95% CI: 0.9, 1.3; P = 0.186) where cesarean delivery prevalence was below 20%. Women with history of genital herpes appear to have a slightly elevated risk of cesarean delivery, particularly in hospital settings with baseline prevalence of primary cesarean delivery above 20%. This rate is somewhat lower than that noted in a previous survey, suggesting that practitioners are following standard guidelines. Evaluations of cesarean delivery for genital herpes in other states should be performed. Infect. Dis. Obstet. Gynecol. 5:29–35, 1997. © 1997 Wiley-Liss, Inc

Published
1997
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43. Rapid Method for Screening Dried Blood Samples on Filter Paper for Human Immunodeficiency Virus Type 1 DNA

Author

Panteleeff, Dana DeVange, John, Grace, Nduati, Ruth, Mbori-Ngacha, Dorothy, Richardson, Barbra, Kreiss, Joan, and Overbaugh, Julie

Abstract

ABSTRACTPCR is a highly sensitive method for the detection of human immunodeficiency virus type 1 (HIV-1) nucleic acids in blood mononuclear cells and plasma. However, blood separation techniques require extensive laboratory support systems and are difficult when a limited volume of blood is available, which is often the case for infants. The use of blood samples stored on filter paper has many advantages for the detection of perinatal HIV-1 infection, but current methods require extraction and purification of target DNA prior to PCR amplification. We report a highly sensitive and rapid method for the extraction and detection of HIV-1 DNA in infant blood samples stored on filter papers. Because this rapid protocol does not involve steps for the removal of potential inhibitors of the PCR, the highest sensitivity is achieved by testing the filter paper lysate in quadruplicate. Assays for HIV-1 DNA were done by using nested PCR techniques that amplify HIV-1 gagDNA from blood spot samples on filter paper and from corresponding viably frozen mononuclear cells separated from venous blood samples obtained from 111 infants born to HIV-1-seropositive mothers. PCR results with blood from filter papers showed 100% specificity (95% confidence internal [CI] 93.1 to 100%) and 96% (95% CI, 88.65 to 98.9%) and 88% (95% CI, 79.2 to 94.5%) sensitivity (for quadruplicate and duplicate tests, respectively) compared to PCR results with blood mononuclear cells. Moreover, this method could detect HIV-1 sequences of multiple subtypes.

Published
1999
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44. Effect of Breastfeeding and Formula Feeding on Transmission of HIV-1 A Randomized Clinical Trial

Author

Nduati, Ruth, John, Grace, Mbori-Ngacha, Dorothy, Richardson, Barbra, Overbaugh, Julie, Mwatha, Anthony, Ndinya-Achola, Jeckoniah, Bwayo, Job, Onyango, Francis E., Hughes, James, and Kreiss, Joan

Abstract

The risk of transmitting human immunodeficiency virus type I (HIV-1) in breast milk is an established one, but its magnitude remains uncertain, and it is not clear whether this risk exceeds that of dying from formula-related diarrhea in developing countries. A randomized trial was started in Nairobi, Kenya, in 1992 to compare mortality and the risk of HIV infection in breast-fed and formula-fed infants. Initially 425 HIV-1–seropositive pregnant women who had received no antiretroviral study were enrolled in the trial. The infant was breast-fed in 212 instances and formula fed in 213. Randomization took place at about 32 weeks. End points were assessed after a median follow-up of 2 years in 401 mother-infant pairs. The study population was primarily of lower socioeconomic status. The median maternal age was 23 years.

Published
2000

47. Cesarean Delivery in Women With Genital Herpes in Washington State, 1989–1991

Author

M. Marrazzo, Jeanne, C. John, Grace, A. Krohn, Marijane, and Corey, Lawrence

Abstract

Objective: The purpose of this study was to determine whether the proportion of cesarean deliveries in pregnant women with a history of genital herpes and no active lesions at birth is higher than that in women with no history of genital herpes, and to determine whether this risk was modified by birth facilities' underlying prevalence of cesarean delivery.

Published
1997
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48. Human Immunodeficiency Virus Type 1-Infected Cells in Breast Milk: Association with Immunosuppression and Vitamin A Deficiency

Author

Nduati, Ruth W., John, Grace C., Richardson, Barbra A., Overbaugh, Julie, Welch, Mary, Ndinya-Achola, Jackoniah, Moses, Stephen, Holmes, King, Onyango, Francis, and Kreiss, Joan K.

Abstract

Breast milk samples from human immunodeficiency virus type 1 (HIV-1)-seropositive women were analyzed by polymerase chain reaction to determine the prevalence and determinants of HIV-1-infected cells in breast milk. Breast milk samples (212) were collected from 107 women, and 58% of the samples had detectable HIV-1 DNA. The proportion of HIV-1-infected cells in the milk samples ranged from 1 to 3255/104 cells. Breast milk samples with detectable HIV-1 DNA were more likely to be from women with absolute CD4 cell counts of <400 (odds ratio, 3.1; 95% confidence interval [CI], 1.5–7.0). Severe vitamin A deficiency (<20 µg/dL) was associated with a 20-fold increased risk of having HIV-1 DNA in breast milk among women with <400 CD4 cells/mm3 (95% CI, 2.1–188.5). Women with CD4 cell depletion, especially those with vitamin A deficiency, may be at increased risk of transmitting HIV-1 to their infants through breast milk.

Published
1995
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49. Cell-Free Human Immunodeficiency Virus Type 1 in Breast Milk

Author

Lewis, Paul, Nduati, Ruth, Kreiss, Joan K., John, Grace C., Richardson, Barbra A., Mbori-Ngacha, Dorothy, Ndinya-Achola, Jeckoniah, and Overbaugh, Julie

Abstract

Breast-feeding may be an important route of human immunodeficiency virus type 1 (HIV-1) vertical transmission in settings where it is routinely practiced. To define the prevalence and quantity of HIV-1 in cell-free breast milk, samples from HIV-1-seropositive women were analyzed by quantitative competitive reverse transcription-polymerase chain reaction (QC-RT-PCR). HIV-1 RNA was detected in 29 (39%) of 75 specimens tested. Of these 29 specimens, 16 (55%) had levels that were near the detection limit of the assay (240 copies/mL), while 6 (21%) had <900 copies/mL. The maximum concentration of HIV-1 RNA detected was 8100 copies/mL. The prevalence of cell-free HIV-1 was higher in mature milk (47%) than in colostrum (27%, P = 0.1). Because mature milk is consumed in large quantities, these data suggest that cell-free HIV-1 in breast milk may contribute to vertical transmission of HIV-1.

Published
1998
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50. Genital Shedding of Human Immunodeficiency Virus Type 1 DNA during Pregnancy: Association with Immunosuppression, Abnormal Cervical or Vaginal Discharge, and Severe Vitamin A Deficiency

Author

John, Grace C., Nduati, Ruth W., Mbori-Ngacha, Dorothy, Overbaugh, Julie, Welch, Mary, Richardson, Barbra A., Ndinya-Achola, Jeckoniah, Bwayo, Job, Krieger, John, Onyango, Francis, and Kreiss, Joan K.

Abstract

The presence of human immunodeficiency virus type 1 (HIV-1) in genital secretions may be a determinant of vertical HIV-1 transmission. Cervical and vaginal secretions from HIV-1–seropositive pregnant women were evaluated to determine prevalence and correlates of HIV-1–infected cells in the genital tract. HIV-1 DNA was detected by polymerase chain reaction in 32% of 212 cervical and 10% of 215 vaginal specimens. Presence of HIV 1 DNA in the cervix was associated with cervical mucopus and a significantly lower absolute CD4 cell count (354 vs. 469, P < .001). An absolute CD4 cell count < 200 was associated with a 9.6-fold increased odds of cervical HIV-1 DNA detection compared with a count 500 (95% confidence interval, 2.8–34.2). Detection of vaginal HIV-1 DNA was associated with abnormal vaginal discharge, lower absolute CD4 cell count, and severe vitamin Adeficiency. Presence of HIV-1–infected cells in genital secretions was associated with immunosuppression and abnormal cervical or vaginal discharge.

Published
1997
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