PubMed Health⌕ Search

Biomedical subjects

Robert Klein

Publications and source records attributed to Robert Klein.

17 recordsLinked to original sources

Multiple urban and asthma-related risks and their association with asthma morbidity in children.

OBJECTIVE: To determine whether a multi-dimensional cumulative risk index (CRI) is a stronger predictor of asthma morbidity in urban, school-aged children with asthma, than poverty or severity alone. METHODS: A total of 163 children with asthma, ages 7-15 years (42% female; 69% ethnic minority) and their primary caregivers completed interview-based questionnaires, focusing on potential cultural, contextual, and asthma-specific risks that can impact asthma morbidity. RESULTS: Higher levels of cumulative risks were associated with more asthma morbidity, after controlling for poverty level or asthma severity. Analyses by ethnic group and subgroup also supported the relationship between the CRI and specific indices of asthma morbidity. CONCLUSIONS: This study demonstrates the utility of multiple-dimensional risk models for predicting variations in asthma morbidity in urban children. Research efforts with urban families who have children with asthma need to consider the context of urban poverty as it relates to children's cultural backgrounds and specific asthma outcomes.

Adolescent↗

Sorghum stay-green QTL individually reduce post-flowering drought-induced leaf senescence.

Sorghum is an important source of food, feed, and biofuel, especially in the semi-arid tropics because this cereal is well adapted to harsh, drought-prone environments. Post-flowering drought adaptation in sorghum is associated with the stay-green phenotype. Alleles that contribute to this complex trait have been mapped to four major QTL, Stg1-Stg4, using a population derived from BTx642 and RTx7000. Near-isogenic RTx7000 lines containing BTx642 DNA spanning one or more of the four stay-green QTL were constructed. The size and location of BTx642 DNA regions in each RTx7000 NIL were analysed using 62 DNA markers spanning the four stay-green QTL. RTx7000 NILs were identified that contained BTx642 DNA completely or partially spanning Stg1, Stg2, Stg3, or Stg4. NILs were also identified that contained sub-portions of each QTL and various combinations of the four major stay-green QTL. Physiological analysis of four RTx7000 NILs containing only Stg1, Stg2, Stg3, or Stg4 showed that BTx642 alleles in each of these loci could contribute to the stay-green phenotype. RTx7000 NILs containing BTx642 DNA corresponding to Stg2 retained more green leaf area at maturity under terminal drought conditions than RTx7000 or the other RTx7000 NILs. Under post-anthesis water deficit, a trend for delayed onset of leaf senescence compared with RTx7000 was also exhibited by the Stg2, Stg3, and Stg4 NILs, while significantly lower rates of leaf senescence in relation to RTx7000 were displayed by all of the Stg NILs to varying degrees, but particularly by the Stg2 NIL. Greener leaves at anthesis relative to RTx7000, indicated by higher SPAD values, were exhibited by the Stg1 and Stg4 NILs. The RTx7000 NILs created in this study provide the starting point for in-depth analysis of stay-green physiology, interaction among stay-green QTL and map-based cloning of the genes that underlie this trait.

Chromosome Mapping↗

Expansion of symmetric exon-bordering domains does not explain evolution of lineage specific genes in mammals.

In order to examine the evolution of lineage specific genes, we analyzed intron phase distributions and exon-bordering domains in primate and rodent specific genes. We found that the expansion of symmetric exon-bordering domains could not explain the evolution of lineage specific genes. Rather internal intron loss of a domain can partially explain the excess of class 1-1 intron phases in the lineage specific genes. We suggest the event that led to excess of symmetric exons in lineage specific genes had little bearing on shaping the phenotypes specific to the individual lineage. Instead, Kruppel-associated box (KRAB) proteins associated with zinc finger C2H2 (zf-C2H2) type are likely to be responsible for the lineage specific function.

Animals↗

Membrane initiated steroid signaling (MISS): computational, in vitro and in vivo evidence for a plasma membrane protein initially involved in genomic steroid hormone effects.

Steroid hormones are indispensable for control of vital processes, development, reproduction and modulation of behavior. Lack or complete dysfunction of glucocorticoid (GC) signaling, in particular, have lethal consequences. Even a minor change in the level of circulating cortisol can be of physiological and clinical significance. Analysis of the action mechanisms of GC is therefore of major importance, especially since natural and synthetic GC are widely used in the therapy of GC-responsive diseases. According to the classical genomic concept of steroid hormone action, the effects of GC are mediated by specific nuclear receptors (GR). Recent findings provide evidence for the existence of additional, plasma membrane (PM) located steroid receptors, which are thought to be responsible for rapid, non-genomic responses. We present evidence for a PM-residing protein, termed "steroid hormone recognition and effector complex" (SHREC), which plays a pivotal role in the complex network of PM-related non-genomic responses leading to GR-mediated genomic effects. This conclusion was drawn from studies using different in vitro and in vivo models of a GC-target: (1) highly purified fractions of osmotically active PM-vesicles isolated from rat and human hepatocytes, (2) a computational model of SHREC generated by the "automated receptor modeling" (ARM) method, (3) rat liver cell lines transfected with a GC-responsive reporter gene construct and (4) young women orally administered with selected steroids. We conclude that SHREC and the GR participate in the same signaling chain, SHREC<-->steroid interaction is the initial step and an interdependent part of the complete GC signal propagation, thus called "membrane initiated steroid signaling" (MISS).

Administration, Oral↗

The reliability of anterior segment lesions as indicators of onchocercal eye disease in Guatemala.

World Health Organization certification criteria for onchocerciasis elimination use anterior segment eye lesion prevalence as an indicator of mass ivermectin treatment program success. Lesions either contain visible microfilaria (noninflammatory punctate keratitis [PK] or microfilariae in anterior chamber [MFAC]), or microfilaria obscured by inflammation (inflammatory PK). To assess the utility of these disease indicators, two experienced ophthalmologists independently examined persons from endemic (N = 325) and nonendemic (N = 348) Guatemalan communities. Thirty-six (11.1%) and nine (2.6%) persons from endemic and nonendemic areas respectively had lesions found by either ophthalmologist (prevalence ratio = 4.3, 95% CI 2.1-8.8, P < 0.001). All lesions in nonendemic areas were inflammatory PK in whom no persons were seropositive for onchocerciasis. Overall, observer agreement was moderate (Kappa = 0.49), and most (61%) discordance occurred with inflammatory PK lesions. Our findings suggest that inflammatory punctate keratitis is neither a specific nor a reliable indicator of onchocercal eye disease. Future prevalence surveys should rely upon noninflammatory lesions as disease indicators.

Animals↗

Sorghum expressed sequence tags identify signature genes for drought, pathogenesis, and skotomorphogenesis from a milestone set of 16,801 unique transcripts.

Improved knowledge of the sorghum transcriptome will enhance basic understanding of how plants respond to stresses and serve as a source of genes of value to agriculture. Toward this goal, Sorghum bicolor L. Moench cDNA libraries were prepared from light- and dark-grown seedlings, drought-stressed plants, Colletotrichum-infected seedlings and plants, ovaries, embryos, and immature panicles. Other libraries were prepared with meristems from Sorghum propinquum (Kunth) Hitchc. that had been photoperiodically induced to flower, and with rhizomes from S. propinquum and johnsongrass (Sorghum halepense L. Pers.). A total of 117,682 expressed sequence tags (ESTs) were obtained representing both 3' and 5' sequences from about half that number of cDNA clones. A total of 16,801 unique transcripts, representing tentative UniScripts (TUs), were identified from 55,783 3' ESTs. Of these TUs, 9,032 are represented by two or more ESTs. Collectively, these libraries were predicted to contain a total of approximately 31,000 TUs. Individual libraries, however, were predicted to contain no more than about 6,000 to 9,000, with the exception of light-grown seedlings, which yielded an estimate of close to 13,000. In addition, each library exhibits about the same level of complexity with respect to both the number of TUs preferentially expressed in that library and the frequency with which two or more ESTs is found in only that library. These results indicate that the sorghum genome is expressed in highly selective fashion in the individual organs and in response to the environmental conditions surveyed here. Close to 2,000 differentially expressed TUs were identified among the cDNA libraries examined, of which 775 were differentially expressed at a confidence level of 98%. From these 775 TUs, signature genes were identified defining drought, Colletotrichum infection, skotomorphogenesis (etiolation), ovary, immature panicle, and embryo.

DNA, Complementary↗

The design and synthesis of a herbicide targeted library of N-[1-(1,3-benzoxazol-2-yl)alkyl]-6-alkyl-1,3,5-triazine-2,4-diamines.

Amino acids were immobilised by attaching them via a carbamate linker to Wang resin. These intermediates were converted to 1-(1,3-benzoxazol-2-yl)alkanamines over three steps, followed by coupling with 4-alkyl-6-chloro-1,3,5-triazine-2-amines to furnish the desired N-[1-(1,3-benzoxazol-2-yl)alkyl]-6-alkyl-1,3,5-triazine-2,4-diamines. Physico-chemical property profiles were used to support design and development of a combinatorial library. The synthetic methodology described herein was validated with the production of a herbicide targeted library of 300 members.

Agrochemicals↗

Toxoplasma gondii infection in rural Guatemalan children.

To determine the prevalence and risk factors for Toxoplasma gondii infection in Guatemalan children, in 1999 and 2003 we surveyed caretakers and serologically tested children in the San Juan Sacatepequez area using Platelia Toxo IgG TMB enzyme immunoassay kits. In 1999, of 532 children six months to two years old, 66 (12.4%) were antibody positive. In 2003, in 500 children 3-10 years old antibody prevalence increased from 24% to 43% at age five years then leveled off. By multivariate analysis, drinking well water (relative risk [RR] = 1.78, 95% confidence limit [CL] = 1.00, 3.17, P = 0.05) and not cleaning up cat feces (RR = 2.06, 95% CL = 1.00, 4.28, P = 0.05) increased the risk of T. gondii seropositivity. Most T. gondii infections in children from these villages occurred by age five, but half were still not infected by adolescence. Therefore, it is important to educate girls entering child-bearing age about the risks of acute T. gondii infection and the local risk factors for infection.

Animals↗

The design and synthesis of novel inhibitors of NADH:ubiquinone oxidoreductase.

Potent new inhibitors of NADH:ubiquinone oxidoreductase (complex I) have been designed, with the help of molecular modelling, by hybridisation of known complex I inhibitors with inhibitors of cytochrome c oxidoreductase. The most interesting compound was the chromone 7 which was a selective inhibitor of complex I (IC(50) 15 nM) and showed acaricidal activity against spider mites.

Animals↗

Prevalence of infection with waterborne pathogens: a seroepidemiologic study in children 6-36 months old in San Juan Sacatepequez, Guatemala.

Water and sanitation interventions in developing countries have historically been difficult to evaluate. We conducted a seroepidemiologic study with the following goals: 1) to determine the feasibility of using antibody markers as indicators of waterborne pathogen infection in the evaluation of water and sanitation intervention projects; 2) to characterize the epidemiology of waterborne diarrheal infections in rural Guatemala, and 3) to measure the age-specific prevalence of antibodies to waterborne pathogens. Between September and December 1999, all children 6-36 months of age in 10 study villages were invited to participate. We collected sufficient serum from 522 of 590 eligible children, and divided them into six-month age groups for analysis (6-12, 13-18, 19-24, 25-30, and 31-36 months). The prevalence of antibodies was lowest in children 6-12 months old compared with the four older age groups for the following pathogens: enterotoxigenic Escherichia coli (48%, 81%, 80%, 77%, and 83%), Norwalk virus (27%, 61%, 83%, 94%, and 94%), and Cryptosporidium parvum (27%, 53%, 70%, 67%, and 73%). The prevalence of total antibody to hepatitis A virus increased steadily in the three oldest age groups (40%, 28%, 46%, 60%, and 76%). In contrast, the prevalence of antibody to Helicobacter pylori was relatively constant in all five age groups (20%, 19%, 21%, 25%, and 25%). Serology appears to be an efficient and feasible approach for determining the prevalence of infection with selected waterborne pathogens in very young children. Such an approach may provide a suitable, sensitive, and economical alternative to the cumbersome stool collection methods that have previously been used for evaluation of water and sanitation projects.

Animals↗

Confirmed detection of Cyclospora cayetanesis, Encephalitozoon intestinalis and Cryptosporidium parvum in water used for drinking.

Human enteropathogenic microsporidia (HEM), Cryptosporidium parvum, Cyclospora cayetanesis, and Giardia lamblia are associated with gastrointestinal disease in humans. To date, the mode of transmission and environmental occurrence of HEM (Encephalitozoon intestinalis and Enterocytozoon bieneusi) and Cyclospora cayetanesis have not been fully elucidated due to lack of sensitive and specific environmental screening methods. The present study was undertaken with recently developed methods, to screen various water sources used for public consumption in rural areas around the city of Guatemala. Water concentrates collected in these areas were subjected to community DNA extraction followed by PCR amplification, PCR sequencing and computer database homology comparison (CDHC). All water samples screened in this study had been previously confirmed positive for Giardia spp. by immunofluorescent assay (IFA). Of the 12 water concentrates screened, 6 showed amplification of microsporidial SSU-rDNA and were subsequently confirmed to be Encephalitozoon intestinalis. Five of the samples allowed for amplification of Cyclospora 18S-rDNA; three of these were confirmed to be Cyclospora cayetanesis while two could not be identified because of inadequate sequence information. Thus, this study represents the first confirmed identification of Cyclospora cayetanesis and Encephalitozoon intestinalis in source water used for consumption. The fact that the waters tested may be used for human consumption indicates that these emerging protozoa may be transmitted by ingestion of contaminated water.

Animals↗

Within- and between-day variability of respiratory impedance, using impulse oscillometry in adolescent asthmatics.

The objectives of the present study were to: 1) assess spirometric indices and respiratory impedance with forced oscillation (FO), using impulse oscillometry (IOS) in clinically stable asthmatic children over 3 consecutive days; 2) assess FO reactance (X), using an integrated index and resistance (R) separately during inspiration and expiration; and 3) assess effects on FO of hand support of cheeks vs. no hand support. Our hypotheses were: 1) because of increased sensitivity, IOS manifests day-to-day variability not demonstrable by spirometry; 2) IOS R during expiration exceeds that during inspiration; and 3) hand support of cheeks affects IOS R and X only minimally. We obtained triplicate twice-daily measures of IOS R and X in asthmatic adolescents at summer camp, in a convenience sample of children willing, with parental permission, to undergo repeated testing on consecutive days. Subjects received all medications between 6:30-7:30 AM, and were bronchodilated at time of testing. Subjects underwent IOS tests without hand support of cheeks, followed by tests with both hands supporting cheeks. ANOVA and regression analyses were used to discern technique differences.Significant differences in IOS inspiratory R5, R5 - R15 (frequency dependence of R), and low frequency reactance area (AX) occurred across 3 days, but spirometric indices were unchanged. Inspiratory R at 5 Hz (R5) was significantly smaller than expiratory R5 (P < 0.0001). ANOVA revealed no significant differences between hand and facial muscle cheek support for IOS R and X below 15 Hz, but significant differences occurred above 15 Hz. In conclusion, inspiratory R5, R5 - R15, and AX are sensitive measures for detecting changes in bronchomotor tone in adolescent asthmatic subjects, while expiratory R5 may be influenced by additional factors. Manual support of cheeks does not appear to affect IOS indices of peripheral airway obstruction in adolescent asthmatics. IOS is a practical method for quantifying respiratory mechanics, and its potential role in disease management warrants further study.

Adolescent↗

Variation in asthma beliefs and practices among mainland Puerto Ricans, Mexican-Americans, Mexicans, and Guatemalans.

This study reports on community surveys of 160 representative Latino adults in Hartford, CT, Edinburg, TX, Guadalajara, Mexico; and in rural Guatemala. A 142-item questionnaire covered asthma beliefs and practices (e.g., causes, symptoms, and treatments). The cultural consensus model was used to analyze the agreement among respondents within each sample and to describe beliefs. Beliefs were then compared across the four samples. Analysis of the questionnaire data shows that there was overall consistency or consensus regarding beliefs and practices among individuals at each site (intraculturally) and to a lesser extent across respondents of all four different Latino cultural groups (i.e., interculturally). This pattern of response is indicative of a shared belief system among the four groups with regard to asthma. Within this shared belief system though, there is systematic variation between groups in causes, symptoms, and treatments for asthma. The most widely recognized and shared beliefs concerned causes of asthma. Notable differences were present between samples in terms of differences in beliefs about symptoms and treatments. The biomedical model is shown to be a part of the explanatory model at all sites; in addition to the biomedical model, ethnocultural beliefs such as the humoral ("hot/cold") aspects and the importance of balance are also evident. The Connecticut Puerto Ricans had a greater degree of shared beliefs about asthma than did the other three samples (p < 0.00005). It was concluded that the four Latino groups studied share an overall belief system regarding asthma, including many aspects of the biomedical model of asthma. In addition, traditional Latino ethnomedical beliefs are present, especially concerning the importance of balance in health and illness. Many beliefs and practices are site-specific, and caution should be used when using inclusive terms such as "Hispanic" or "Latino," since there is variation as well as commonality among different ethnic groups with regard to health beliefs and practices.

Adult↗

The next big thing.

Explore the source record for details and available documents.

California↗

Chronic cough: an interactive case discussion.

The following case was presented at the Eastern Allergy Conference May 2005 to each of four small group sessions in an attempt to incorporate problem-based learning (PBL) into the curriculum of the conference for the first time in its 18-year history. Before this, the format had always been non-stop lectures for four days. The attempt to use PBL in breakout sessions was due to the well-documented improved learning experience with PBL demonstrated by multiple studies in the literature of PBL for CME. This PBL case on an adult who presents with a "chronic cough" was linked to a series of three didactic lectures to reinforce the differential diagnoses in this patient. The three lectures followed the PBL breakout sessions (during the morning of the conference) and were entitled Laryngeal Pharyngeal Reflux (LPR), Chronic Sinusitis: A Surgical Perspective and Chronic Cough. Although the best learning scenario for this case occurs when there is interaction with one's peers, review of this case and answering the questions that were posed by the facilitators can still provide a great learning experience.

Adult↗