Winston A. Anderson

Cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in Ghanaian children

BackgroundPlasmodium falciparum can cause a diffuse encephalopathy known as cerebral malaria (CM), a major contributor to malaria associated mortality. Despite treatment, mortality due to CM can be as high as 30% while 10% of survivors of the disease may experience short- and long-term neurological complications. The pathogenesis of CM and other forms of severe malaria is multi-factorial and appear to involve cytokine and chemokine homeostasis, inflammation and vascular injury/repair. Identification of prognostic markers that can predict CM severity will enable development of better intervention.MethodsPostmortem serum and cerebrospinal fluid (CSF) samples were obtained within 2–4 hours of death in Ghanaian children dying of CM, severe malarial anemia (SMA), and non-malarial (NM) causes. Serum and CSF levels of 36 different biomarkers (IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, Eotaxin, FGF basic protein, CRP, G-CSF, GM-CSF, IFN-γ, TNF-α, IP-10, MCP-1 (MCAF), MIP-1α, MIP-1β, RANTES, SDF-1α, CXCL11 (I-TAC), Fas-ligand [Fas-L], soluble Fas [sFas], sTNF-R1 (p55), sTNF-R2 (p75), MMP-9, TGF-β1, PDGF bb and VEGF) were measured and the results compared between the 3 groups.ResultsAfter Bonferroni adjustment for other biomarkers, IP-10 was the only serum biomarker independently associated with CM mortality when compared to SMA and NM deaths. Eight CSF biomarkers (IL-1ra, IL-8, IP-10, PDGFbb, MIP-1β, Fas-L, sTNF-R1, and sTNF-R2) were significantly elevated in CM mortality group when compared to SMA and NM deaths. Additionally, CSF IP-10/PDGFbb median ratio was statistically significantly higher in the CM group compared to SMA and NM groups.ConclusionThe parasite-induced local cerebral dysregulation in the production of IP-10, 1L-8, MIP-1β, PDGFbb, IL-1ra, Fas-L, sTNF-R1, and sTNF-R2 may be involved in CM neuropathology, and their immunoassay may have potential utility in predicting mortality in CM.

Synthesis of Toughened Elastomer from Vernonia galamensis Seed Oil

AbstractsThis paper examines the synthesis of a toughened elastomer fromVernonia galamensis seed oil by reacting vernonia oil with vernonia oil-derived suberic acid (octanedioic acid), and cross-linking the pre-polymer in the immediate presence of cross-linked polystyrene preparedin situ. The paper also demonstrates that the progress of reaction can be followed by monitoring the generation of hydroxyl groups using infrared spectroscopy. Analysis of some crystalline material on the cooler parts of the reaction vessels revealed the presence of component fatty acids of vernonia oil. Transmission electron microscopy characterization of the synthesized toughened elastomer suggests that vernonia oil-suberic acid polyester and polystyrene polymer are interpenetrating.

The preparation of stroma-free hemoglobin by selective DEAE-cellulose absorption

The preparation of stroma-free hemoglobin by selective DEAE-cellulose absorption is reported. The stroma-free hemoglobin prepared by this method is compared to the product obtained by crystallization from sodium phosphate. Both show normal serum potassium, sodium, and pH values, and no coagulant activity or blood type activity by blood type test. PAA gradient gel electrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and isoelectric focusing in polyacrylamide gel all show the same well-defined bands in both preparations. The DEAE procedure requires 11 h as compared to 4 days for the crystallization method. The recovery of hemoglobin is 77% (less than 1% methemoglobin) in the DEAE preparation compared to 34% (greater than 3% methemoglobin) by the crystallization method. In addition, far fewer expensive materials are required.

Effect of high-dose estrogen on growth and steroid receptor activity in DMBA-induced mammary tumors and uteri of rats.

High doses of estrogen (5-500 micrograms) induce regression of hormone-dependent DMBA mammary tumors in rats at the same rate and degree as treatment with the antiestrogen C1628 (Parke-Davis). In contrast, high dose estrogen stimulated growth of uteri in tumor-bearing rats, while C1628 was antiuterotrophic. Within 72 h following treatment with estrogen, diethylstilbestrol (DES), or C1628, changes in the levels of estrogen receptor (ER) and progesterone receptor (PgR) were evident in both uterine and mammary tumor tissue. Both estrogen and antiestrogen induced depression of the total cytosolic ER and altered the 8S/4S receptor ratio. The tumor cytosolic ER levels of DES- and C1628-treated rats were 4.67 +/- 1.7 fmol/mg protein and 15.89 +/- 3.1 fmol/mg protein, respectively, compared to 48.89 +/- 13.6 fmol/mg protein in tumors of untreated rats. In spite of reduced levels of cytosolic ER, there was an apparent increase in the 8S/4S ratio (62% increase in 8S/4S ER ratio compared to control 8S/4S ratio; p less than 0.05). Total uterine cytosolic ER was low after treatments with DES (5.69 +/- 2.08 fmol/mg protein) or C1628 (94.76 fmol/mg +/- 30.3 fmol/mg protein), as compared to untreated controls (188.2 +/- 7.6 fmol/mg protein). The cytosolic PgR was consistently high in tumors of control rats (42.99 +/- 11.9 fmol/mg protein) and in castrated rats treated with high doses of DES or C1628 (DES, 55.15 +/- 27.0; C1628, 65.07 +/- 9.8 protein).

Nephrotoxic Effects of Oxygen Transport Media in the Isolated Rat Kidney

Abstract Perfusion of isolated kidneys from rats demonstrated the following nephrotoxic effects of Fluosol-DA: decreased glomerular filtration rate (GFR), urine flow rate (UFR), and fractional reabsorption of potassium (FrK+) (P < 0.01). Fluosol-DA perfusions were at flow rates about equal to the physiologically normal rodent renal plasma flow rate of 4 ml/min. Stroma-free hemoglobin (SFH) perfusions, also at 4 ml/min, were associated with physiologically normal renal functions, as were those of control Krebs-Ringer bicarbonate (KRB) perfusions at 32 ml/min.

Genome Sequence of Mycobacteriophage ErnieJ

ABSTRACT ErnieJ, a cluster C mycobacteriophage that infects Mycobacterium smegmatis mc2155, was recovered from soil in Washington, DC. Its genome is 153,243 bp in size and encodes 227 predicted proteins, 30 tRNAs, and one transfer-messenger RNA (tmRNA). Ten percent of the predicted proteins have homologs in phages that infect nonmycobacterial Actinobacteria.