Immunohematological reference ranges for adult Ethiopians

A cross-sectional survey was carried out with 485 healthy working adult Ethiopians who are participating in a cohort study on the progression of human immunodeficiency virus type 1 (HIV-1) infection to establish hematological reference ranges for adult HIV-negative Ethiopians. In addition, enumeration of absolute numbers and percentages of leukocyte subsets was performed for 142 randomly selected HIV-negative individuals. Immunological results were compared to those of 1,356 healthy HIV-negative Dutch blood donor controls. Immunohematological mean values, medians, and 95th percentile reference ranges were established. Mean values were as follows: leukocyte (WBC) counts, 6.1 x 10(9)/liter (both genders); erythrocyte counts, 5.1 x 10(12)/liter (males) and 4.5 x 10(12)/liter (females); hemoglobin, 16.1 (male) and 14.3 (female) g/dl; hematocrit, 48.3% (male) and 42.0% (female); platelets, 205 x 10(9)/liter (both genders); monocytes, 343/microl; granulocytes, 3, 057/microl; lymphocytes, 1,857/microl; CD4 T cells, 775/microl; CD8 T cells, 747/microl; CD4/CD8 T-cell ratio, 1.2; T cells, 1, 555/microl; B cells, 191/microl; and NK cells, 250/microl. The major conclusions follow. (i) The WBC and platelet values of healthy HIV-negative Ethiopians are lower than the adopted reference values of Ethiopia. (ii) The absolute CD4 T-cell counts of healthy HIV-negative Ethiopians are considerably lower than those of the Dutch controls, while the opposite is true for the absolute CD8 T-cell counts. This results in a significantly reduced CD4/CD8 T-cell ratio for healthy Ethiopians, compared to the ratio for Dutch controls.     

Experimental comparison of the thrombogenicity of fibrin and PTFE flow surfaces

Two types of 4 mm ID prostheses were studied in the carotid arteries of the dog. These were noncrimped polypropylene-supported filamentous velour knitted Dacron (PPSFV) and expanded polytetrafluoroethylene (e-PTFE, Gore-Tex). Thrombus-"Free" Surface TFS) areas and patency rates were determined at the end of the implant periods. One series of implants was subjected to controlled low flow rates for six hours; another was exposed to physiologic flow rates and observed at seven days, 14 days, and 12 weeks. At six hours the filamentous Dacron, preclotted according to a specific regimen utilizating heparin, performed as well as, and possibly better than, e-PTFE. The Gore-Tex developed surface coagulum in an irregular fashion which was related to graft wetting and blood soakage. Seven-day TFS scores and patency rates of the two graft types were comparable at physiologic flow rates. At two weeks, TFS scores and patency rates of the two graft types were comparable at physiologic flow rates. At two weeks, TFS scores and patency rates dropped. This was sufficiently marked in the case of e-PTFE that longer-term implants were not done. However, PPSFV grafts were implanted for 12 weeks, and all grafts examined at that time had closed. It appears that patency of 4 mm ID grafts of this construction will not be reliably attained in the dog carotid artery without the use of platelet-inhibitory drugs until complete healing has occurred.     

Development and validation of a delayed presenting clubfoot score to predict the response to Ponseti casting for children aged 2–10

The aim of the study was to develop a simple and reliable clinical scoring system for delayed presenting clubfeet and assess how this score predicts the response to Ponseti casting. We measured all elements of the Diméglio and the Pirani scoring systems. To determine which aspects were useful in assessing children with delayed presenting clubfeet, 4 assessors examined 42 feet (28 patients) between the ages of 2–10 years. Selected variables demonstrating good agreement were combined to make a novel score and were assessed prospectively on a separate consecutive cohort of children with clubfeet aged 2–10, comprising 100 clubfeet (64 patients). Inter-observer and intra-observer agreement was found to be greatest using the following clinically measured angles of the deformities. These were plantaris, adductus, varus, equinus of the ankle and rotation around the talar head in the frontal plane (PAVER). Measured angles of 1–20, 21–45 and?>?45 degrees scored 1, 2 and 3 points, respectively. The PAVER score was derived from both the sum of points derived from measured angles and a multiplier according to age. The sum of the points was multiplied with 1, 1.5 or 2 for ages 2–4, 5–7 and 8–10, respectively. This demonstrated a good association with the total number of casts to achieve a full correction (tau?=?0.71). A score greater than 18 out of 30 indicated a cast-resistant clubfoot. The score could be used clinically for prognosis and treatment, and for research purposes to compare the severity of clubfoot deformities.     

Prevalence and correlates of dyslipidemia in HIV positive and negative adults in Western Kenya: A cross-sectional study

There is increasing morbidity and mortality from cardiovascular diseases (CVD) in sub-Saharan Africa (SSA). Dyslipidemia is a well-known CVD risk factor which has been associated with human immunodeficiency virus (HIV) infection and its treatment in high-income countries. Studies in SSA that have examined the relationship between HIV and dyslipidemia have reported mixed results. In this study, we sought to determine the prevalence of dyslipidemia in HIV positive and negative adults (>=30 years old) and evaluate for association in Western Kenya with a higher prevalence expected among HIV positive individuals.HIV positive adults receiving antiretroviral therapy (ART) and HIV negative individuals seeking HIV testing and counseling services were recruited into a cross-sectional study. Demographic and behavioral data and fasting blood samples were collected. Dyslipidemia was defined according to the National Cholesterol Education Program Adult Treatment Panel III. Associations between baseline demographic and clinical variables and dyslipidemia were analyzed using logistic regression.A total of 598 participants, 300 HIV positive and 298 HIV negative adults were enrolled. Dyslipidemia data was available for 564 (94%) participants. In total, 267 (47%) had dyslipidemia. This was not significantly different between HIV positive and HIV negative individuals (46% vs 49%, P = .4). In a multivariate analysis including both HIV positive and negative individuals, adults 50 to 59 years of age had a 2-fold increased risk of dyslipidemia (Odds ratio [OR] 2.1, 95% confidence interval (1.2–3.5) when compared to 30 to 39-years-old participants. Abdominal obesity (OR 2.5), being overweight (OR 1.9), and low fruit and vegetable intake (OR 2.2) were significantly associated with dyslipidemia. Among HIV positive participants, time since HIV diagnosis, ART duration, use of (PI) protease inhibitor-based ART, viral load suppression, current cluster of differentiation (CD4) count and nadir CD4 did not have significant associations with dyslipidemia.The prevalence of dyslipidemia is high in Western Kenya, with nearly half of all participants with lipid abnormalities. Dyslipidemia was not significantly associated with HIV status, or with HIV-specific factors. Older age, being overweight, abdominal obesity, and low fruit and vegetable intake were associated with dyslipidemia and may be targets for public health interventions to lower the prevalence of dyslipidemia and CVD risk in sub-Saharan Africa.     

Osteoporosis in pulmonary clinic patients: does point-of-care screening predict central dual-energy X-ray absorptiometry?

STUDY OBJECTIVES: Patients in a pulmonary clinic have disorders that predispose them to osteoporosis and may use glucocorticoid therapy, which has been associated with low bone mineral density (BMD) and increased fracture risk. Ideally, all patients at risk for osteoporosis would be screened using the best test available, which is central BMD by dual-energy x-ray absorptiometry (DXA). We proposed to stratify the risk for osteoporosis by the use of a simple questionnaire and point-of-care heel ultrasound BMD measurements. DESIGN: Cross-sectional screening study. SETTING: Pulmonary clinic in a single Veterans Affairs Medical Center. PATIENTS: Approximately 200 male and female patients who had not had previous BMD testing were eligible for the study, and 107 gave consent. INTERVENTIONS: One hundred seven men (white, 71 men; black, 35 men; and Asian, 1 man) underwent heel BMD testing and filled out a questionnaire. Ninety-eight men underwent a central DXA. RESULTS: Of 98 subjects, 24.5% had a spine, total hip, or femoral neck (FN) T-score of or= 7 days, and race, which accounted for 52 to 57% of the variance. When a heel ultrasound T-score of -1.0 was tested to predict a central DXA T-score of -2.0, the sensitivity was 61% and the specificity 64%. Adding the questionnaire score and body mass index (BMI) to the heel T-score improved sensitivity but not specificity. Moreover, BMI and age predicted central BMD with similar sensitivity and specificity. Importantly, of 24 patients with a central DXA T-score of 相似文献   

Homology modeling in drug discovery: Overview,current applications,and future perspectives

Homology modeling is one of the computational structure prediction methods that are used to determine protein 3D structure from its amino acid sequence. It is considered to be the most accurate of the computational structure prediction methods. It consists of multiple steps that are straightforward and easy to apply. There are many tools and servers that are used for homology modeling. There is no single modeling program or server which is superior in every aspect to others. Since the functionality of the model depends on the quality of the generated protein 3D structure, maximizing the quality of homology modeling is crucial. Homology modeling has many applications in the drug discovery process. Since drugs interact with receptors that consist mainly of proteins, protein 3D structure determination, and thus homology modeling is important in drug discovery. Accordingly, there has been the clarification of protein interactions using 3D structures of proteins that are built with homology modeling. This contributes to the identification of novel drug candidates. Homology modeling plays an important role in making drug discovery faster, easier, cheaper, and more practical. As new modeling methods and combinations are introduced, the scope of its applications widens.     

Siah2‐deficient mice show impaired skin wound repair

Hypoxia is associated with the dermal wound healing process and hypoxia signaling is presumed to be crucial for normal wound repair. The Siah2 ubiquitin ligase controls the abundance of hypoxia‐inducible factor‐1 alpha, and loss of Siah2 results in destabilization of hypoxia‐inducible factor‐1 alpha under hypoxia. Utilizing Siah2^?/? mice we demonstrate that cutaneous wound healing is impaired in these mice. Wounds in Siah2^?/? mice heal slower and are associated with delayed induction of myofibroblast infiltration and reduced collagen deposition. This coincides with delayed angiogenesis and reduced macrophage infiltration into the wounds of Siah2^?/? mice. We furthermore demonstrate that primary Siah2^?/? dermal fibroblasts have reduced migratory capacities and produce less collagen than wild‐type fibroblasts. Additionally, Siah2^?/? fibroblasts showed conserved responses to transforming growth factor‐β at the receptor level (pSmad 2C activation) but reduced responses downstream. Together, our data show, for the first time, that Siah2 is involved as a positive regulator in the wound healing response. Understanding the role of hypoxia signaling in tissue repair and fibrosis and interference with the hypoxia signaling pathway via regulation of Siah2 may provide new targets for clinical regulation of fibrosis and scarring.     

Progesterone and RU486: opposing effects on human sperm.

Progesterone induced a rapid influx of calcium in capacitated human sperm, followed by a long-lasting, dose-dependent increase of intracellular free calcium. Thereafter, progesterone increased the fraction of hyperactivated sperm and the acrosome reaction. On the contrary, the progesterone antagonist RU486 (mifepristone) induced an immediate and transient, dose-dependent decrease of intracellular free calcium and a drop in the values of sperm movement parameters related to hyperactivation. Moreover, RU486 counteracted the effects of progesterone on calcium influx, lateral sperm head displacement, and the acrosome reaction. Therefore, RU486 effects were opposite to those of progesterone. The nature of the membrane receptor(s) involved is unknown. Several steroids bearing 11 beta-phenyl substitutions, with different pharmacological profiles, were also investigated. It was concluded that the steroid structure and chemical groups added to the 11 beta-phenyl influence effects on calcium influx.     

Stimulation of protein-tyrosine phosphorylation in rat striatum after lesion of dopamine neurons or chronic neuroleptic treatment.

Even though the short-term actions of dopamine on postsynaptic receptors are well-characterized, the molecular bases for long-term trophic interactions between dopamine neurons and their targets remain unclear. Since protein-tyrosine phosphorylation plays a key role in the action of trophic factors, we have investigated its possible involvement in the interactions between dopamine neurons and their striatal targets. Lesioning rat nigrostriatal dopamine neurons by using 6-hydroxydopamine increased the phosphorylation on tyrosine of several proteins, including a major 180-kDa protein (pp180) in the ipsilateral striatum. Protein-tyrosine kinase activity was also increased in the striatum ipsilateral to the lesion, whereas no change in phosphotyrosine phosphatase activity was detected. The stimulation of pp180 phosphorylation was observed 1, 2, and 8 weeks after 6-hydroxydopamine lesion, was selective for the destruction of dopamine neurons, and was mimicked by chronic blockade of dopamine receptors with neuroleptics. Additional lesion experiments and subcellular fractionation showed that pp180 is located in neuronal postsynaptic densities, suggesting that pp180 is a postsynaptic component of corticostriatal synapses. Our results indicate that lesion of specific afferent fibers can activate tyrosine phosphorylation in central neurons and suggest that tyrosine phosphorylation is involved in the long-term consequences of dopamine deficiency and may play a role in synaptic plasticity.