Levels of organochlorine pesticides residues in milk of urban mothers in Kenya

Organochlorine compounds (OCPs) are toxic products capable of producing serious adverse health consequences. When used to control pests, certain OCPs persist in the environment and accumulate in the fatty tissues of living organisms, reaching higher levels in animals higher in the food chain. Many countries have therefore either restricted or banned the use of OCPs. DDT used to be widely used in Kenya to control pests, but is now used only to control mosquito populations. The contamination of human milk by organochlorine and other related compounds is a major concern in many parts of the world. Findings are reported from a study conducted to assess the levels of OCPs in an urban area of Kenya and to compare OCP levels in human milk from a previous study in rural areas of the country. 216 milk samples were collected from mothers aged 18-30 years in hospital maternity wards or attending postnatal clinics in selected areas in Nairobi in 1991. All mothers involved in the study were nursing either their first or second child, and had lived in Nairobi for at least 5 years before the date of sampling. Samples were collected from mothers who were up to 4 weeks postpartum and analyzed for the presence of OCP residues. 9 OCPs were detected, with p,p'DDT and p,p'DDE being the most frequently encountered contaminants in all samples analyzed. p,p'DDE was detected in 99.5% and p,p'DDT in 78.2% of all samples. Other residues detected were dieldrin (27%), beta-HCH (18.5%), lindane (12%), and alpha-HCH (8.8%). Levels of sum DDT ranged from 0.004 to 6.321 mg/kg fat. Mothers living in Nairobi have low levels of OCPs in their breast milk compared to mothers in rural areas. The relatively lower urban levels could be attributed to the restricted use of OCPs. People need to be taught how to safely use pesticides.     

Disruption of cellular translational control by a viral truncated eukaryotic translation initiation factor 2alpha kinase homolog

Phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha) is a common cellular mechanism to limit protein synthesis in stress conditions. Baculovirus PK2, which resembles the C-terminal half of a protein kinase domain, was found to inhibit both human and yeast eIF2alpha kinases. Insect cells infected with wild-type, but not pk2-deleted, baculovirus exhibited reduced eIF2alpha phosphorylation and increased translational activity. The negative regulatory effect of human protein kinase RNA-regulated (PKR), an eIF2alpha kinase, on virus production was counteracted by PK2, indicating that baculoviruses have evolved a unique strategy for disrupting a host stress response. PK2 was found in complex with PKR and blocked kinase autophosphorylation in vivo, suggesting a mechanism of kinase inhibition mediated by interaction between truncated and intact kinase domains.     

An ester bond linking a fragment of a serine proteinase to its serpin inhibitor

Most known members of the serpin superfamily are serine proteinase inhibitors. Serpins are therefore important regulators of blood coagulation, complement activation, fibrinolysis, and turnover of extracellular matrix. Serpins form SDS-resistant complexes of 1:1 stoichiometry with their target proteinases by reaction of their P1-P1' peptide bond with the active site of the proteinases. The nature of the interactions responsible for the high stability of the complexes is a controversial issue. We subjected the complex between the serine proteinase urokinase-type plasminogen activator (uPA) and the serpin plasminogen activator inhibitor-1 (PAI-1) to proteolytic digestion under nondenaturing conditions. The complex could be degraded to a fragment containing two disulfide-linked peptides from uPA, one of which included the active site Ser, while PAI-1 was left undegraded. By further proteolytic digestion after denaturation and reduction, it was also possible to degrade the PAI-1 moiety, and we isolated a fragment containing 10 amino acids from uPA, encompassing the active site Ser, and 6 amino acids from PAI-1, including the P1 Arg. Characterization of the fragment gave results fully in agreement with the hypothesis that it contained an ester bond between the hydroxyl group of the active site Ser and the carboxyl group of the P1 Arg. These data for the first time provide direct evidence that serine proteinases are entrapped at an acyl intermediate stage in serine proteinase-serpin complexes.     

Synchronization of cells in the S phase of the cell cycle by 3'-azido-3'-deoxythymidine: implications for cell cytotoxicity

The mechanism of synergy between 3'-azido-3'-deoxythymidine (AZT) and anticancer agents was investigated with emphasis on cell-cycle events. Exposure of exponentially growing WiDr human colon carcinoma cells to AZT resulted in synchronization of cells in the S phase of the cell cycle. Following treatment with AZT at 50 or 200 microM, 62% +/- 3% or 82% +/- 4% of the cells were in the S phase as compared with 36% +/- 2% in the control. Bromodeoxyuridine uptake studies revealed that the synchronized cells actively synthesized DNA. At concentrations of up to 200 microM, AZT produced a cytostatic rather than cytotoxic effect as indicated by viability and cell growth measurements. At 200 microM, AZT-induced synchronization was significant (P = < 0.001) after 12 h of drug exposure, reached a maximum at 24 h, and reversed to baseline levels by 72 h even in the continued presence of the drug. This indicates that AZT-induced cytostasis is a transient and reversible effect. The cell-cycle events seen with AZT in WiDr cells were also observed in eight of nine human tumor cell lines tested. Isobologram analysis of WiDr cells preexposed to AZT for 24 h and then exposed to either AZT-5-fluorouracil or AZT-methotrexate for a further 72 h revealed synergy between AZT and the anticancer agents, indicating that AZT-induced synchronization may have therapeutic benefits.     

Transplantation. Abstract from 1970

We previously suggested that hydroxyl free radical (-OH) production may play a role in carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). MNNG-induced gastric cancer in rats and human gastric carcinoma occur most often in the antral mucosa and rarely in the normal fundic mucosa. We hypothesized that regional differences in anti-oxidant activity may be responsible. In the present study, we examined anti-oxidant activity by comparing the relative rates of reduction of a nitroxide free radical, 4-hydroxy-2,2,6,6-tetramethyl-1-piperidinyloxy (Tempol), in the antral and fundic mucosa of male Wistar rats using ESR. The relative rate of Tempol reduction was significantly slower in the antral portion of the wall than in the fundic portion when Tempol [4 x 10(-6) mole/mg wet weight of gastric wall] in HEPES buffer (pH 7.4) was spread over the mucosal surface of a section of the gastric wall. Addition of a sulfhydryl group modulator, N-ethylmaleimide, to the mucosal surface before treatment with Tempol removed the significant difference observed in the rates of reduction in the antral and fundic portions of the gastric wall. No signals were detected in the muscle layer. Our results indicate that the relative rate of free radical reduction by sulfhydryl groups was significantly slower in the antral mucosa than in the fundic mucosa. We therefore conclude that a regional difference in the rates of reduction of free radicals by sulfhydryl groups may result in the site susceptible to development of MNNG-induced gastric cancer.     

N-1-tert-butyl-substituted quinolones: in vitro anti-Mycobacterium avium activities and structure-activity relationship studies

We determined the MICs of 63 quinolones against 14 selected reference and clinical strains of the Mycobacterium avium-Mycobacterium intracellulare complex. Sixty-one of the compounds were selected from the quinolone library at Parke-Davis, Ann Arbor, Mich., including N-1-tert-butyl-substituted agents. T 3761 and tosufloxacin were also tested. The activities of all 63 compounds were compared with those of ciprofloxacin and sparfloxacin. The results showed 45 of the quinolones to be active against the M. avium-M. intracellulare complex, with MICs at which 50% of the strains were inhibited (MIC50s) of less than 32 micrograms/ml. Twenty-four of these quinolones had activities equivalent to or greater than that of ciprofloxacin, and nine of them had activities equivalent to or greater than that of sparfloxacin. The most active compounds were the N-1-tert-butyl-substituted quinolones, PD 161315 and PD 161314, with MIC50s of 0.25 microgram/ml and MIC90s of 1 microgram/ml; comparable values for ciprofloxacin were 2 and 4 micrograms/ml, respectively, while for sparfloxacin they were 1 and 2 micrograms/ml, respectively. The next most active compounds, with MIC50s of 0.5 microgram/ml and MIC90s of 1 microgram/ml, were the N-1-cyclopropyl-substituted quinolones, PD 138926 and PD 158804. These values show that the tert-butyl substituent is at least as good as cyclopropyl in rendering high levels of antimycobacterial activity. However, none of the quinolones showed activity against ciprofloxacin-resistant laboratory-derived M. avium-M. intracellulare complex strains. A MULTICASE program-based structure-activity relationship analysis of the inhibitory activities of these 63 quinolones and 109 quinolones previously studied against the most resistant clinical strain of M. avium was also performed and led to the identification of two major biophores and two biophobes.     

Outbreak of Salmonella serotype Hartford infections associated with unpasteurized orange juice

CONTEXT: Acidic foods such as orange juice have been thought to be unlikely vehicles of foodborne illness. OBJECTIVE: To investigate an outbreak of Salmonella enterica serotype Hartford (Salmonella Hartford) infections among persons visiting a theme park in Orlando, Fla, in 1995. DESIGN: Review of surveillance data, matched case-control study, laboratory investigation, and environmental studies. SETTING: General community. PARTICIPANTS: The surveillance case definition was Salmonella Hartford or Salmonella serogroup C1 infection in a resident of or a visitor to Orlando in May or June 1995. In the case-control study, case patients were limited to theme park hotel visitors and controls were matched to case patients by age group and hotel check-in date. MAIN OUTCOME MEASURES: Risk factors for infection and source of implicated food. RESULTS: Sixty-two case patients from 21 states were identified. Both Salmonella Hartford and Salmonella enterica serotype Gaminara (Salmonella Gaminara) were isolated from stool samples of 1 ill person. Thirty-two case patients and 83 controls were enrolled in the case-control study. Ninety-seven percent of case patients had drunk orange juice in the theme park vs 54% of controls (matched odds ratio, undefined; 95% confidence interval, 5.2 to undefined). The orange juice was unpasteurized and locally produced. Salmonella Gaminara was isolated from 10 of 12 containers of orange juice produced during May and July, indicating ongoing contamination of juice probably because of inadequately sanitized processing equipment. CONCLUSIONS: Unpasteurized orange juice caused an outbreak of salmonellosis in a large Florida theme park. All orange juice was recalled and the processing plant closed. Pasteurization or other equally effective risk-management strategies should be used in the production of all juices.     

Characterization of multijoint finger stiffness: dependence on finger posture and force direction

The two-dimensional static stiffness of the index finger was measured with the interphalangeal joints in flexed and extended postures. The stiffness of the relaxed finger was compared with the stiffness when voluntary force was exerted in different directions. The finger stiffness was found to be anisotropic, with the direction of greatest stiffness being approximately parallel to the proximal phalange of the finger. This direction was relatively unaffected by finger posture or direction of finger force. Finger stiffness was more anisotropic when the interphalangeal joints were extended than flexed. The stiffness was most anisotropic when the interphalangeal joints were extended and force was being exerted in the direction of pointing, while it was least anisotropic when the interphalangeal joints were flexed and force was being exerted in directions normally associated with pinching and tapping actions. The stiffness of the individual finger joints was computed and the relation between stiffness and joint torque was examined. Previous studies, which examined single finger joints in isolation, had found that joint stiffness varied in a linear fashion with net joint torque. In contrast, we did not find a monotonic relation between joint stiffness and net joint torque, which we attributed to the need to vary the amount of cocontraction of antagonistic muscles when controlling the direction of finger force.