High dimensional analysis reveals distinct NK cell subsets but conserved response to stimulation in umbilical cord blood and adult peripheral blood

Growing interest surrounds adoptive cellular therapies utilizing Natural Killer (NK) cells, which can be obtained from various sources, including umbilical cord blood (UCB) and adult peripheral blood (APB). Understanding NK cell receptor expression and diversity in such cellular sources will guide future therapeutic designs. We used a 20-color flow cytometry panel to compare unstimulated and cytokine-activated UCB and APB NK cells. Our analysis showed that UCB NK cells express slightly higher levels of the immune checkpoints PD-1, TIGIT, and CD96 compared to their APB counterparts. Unsupervised hierarchical clustering and dimensionality reduction analyses revealed enrichment in CD56^neg as well as mature NKp46^neg and CD56⁺CD16⁺ NK cell populations in UCB whereas CD57⁺ terminally differentiated NK cells with variable expression of KIRs and CD16 were found in APB. These populations were conserved following stimulation with IL-12, IL-15, and IL-18. Cytokine stimulation was associated with the downregulation of TIGIT and CD16 on multiple NK cell subsets in UCB and APB. Among UCB CD16⁻ NK cell populations, TIGIT⁺ NK cells produced more IFN-γ than their TIGIT⁻ counterparts. Our data demonstrate higher immune checkpoint expression on UCB NK cells compared to APB. However, the expression of TIGIT immune checkpoint is not indicative of NK cell exhaustion.     

Pesticide exposure in a farming village in Venezuela--a developing country

This study was designed and performed by the Universidad de Carabobo, Centro de Investigaciones Toxicológicas, Venezuela, and the University of Cincinnati Department of Environmental Health. The authors tested methodology and analyzed preliminary data on demographics, pesticide use, health, environment, and lifestyles in a farming community in Venezuela (population = 386; sample size = 81) to determine if pesticide misuse might have been contributing to public health problems. Questionnaire and geographic information were collected. There were statistically significant incidences of pesticide-related symptoms (p < .01) in farmers versus nonfarmers (odds ratio = 5.7; 95% confidence interval = 2.9, 18.8). In addition, in one area there was a cluster of farmers who experienced symptoms that appeared to be the result of foul air and proximity to farms where there was pesticide use. The results of the study indicated that this public health problem may have been associated with pesticide misuse; however, additional studies are needed to corroborate the findings.     

An international outbreak of Vero cytotoxin-producing Escherichia coli O157 infection amongst tourists; a challenge for the European infectious disease surveillance network

In March 1997, an outbreak of Vero cytotoxin-producing Escherichia coli O157 (VTEC) infection occurred amongst holidaymakers returning from Fuerteventura, Canary Islands. For the investigation, a confirmed case was an individual staying in Fuerteventura during March 1997, with either E. coli O157 VTEC isolated in stool, HUS or serological evidence of recent infection; a probable case was an individual with bloody diarrhoea without laboratory confirmation. Local and Europe-wide active case finding was undertaken through national centres, Salm-Net and the European Programme of Intervention Epidemiology, followed by a case-control study. Fourteen confirmed and one probable case were identified from England (7), Finland (5), Wales (1), Sweden (1) and Denmark (1) staying in four hotels. Three of the four hotels were supplied with water from a private well which appeared to be the probable vehicle of transmission. The case-control study showed illness was associated with consumption of raw vegetables (OR 8.4, 95% CI 1-5-48.2) which may have been washed in well water. This investigation shows the importance of international collaboration in the detection and investigation of clusters of enteric infection.     

Vasodilatory effect in rat aorta of eriodictyol obtained from Satureja obovata

The vasodilator effect of eriodictyol (5,7,3',4'-tetrahydroxyflavanone), isolated previously from the medicinal plant Satureja obovata Lag., was studied in rat thoracic aorta rings. Eriodictyol relaxed in a concentration-dependent manner the noradrenaline (10(-6) M) and KCl (80 mM) induced contractions. The relaxant effect was more potent in noradrenaline precontracted preparations (IC50 = 6.11 +/- 0.2 x 10(-5) M) than in those precontracted with KCl (IC50 = 2.96 +/- 0.1 x 10(-4) M). Eriodictyol produced weakly concentration-dependent inhibition of the phasic component induced by KCl and noradrenaline while the inhibition of the tonic phase of these contractions was more pronounced. These effects were endothelium independent. In addition, eriodictyol (10(-5) and 5 x 10(-5) M) inhibited CaCl2 cumulative concentration response curves. Eriodictyol weakly inhibited the release of calcium from the sarcoplasmic reticulum and its contribution to the relaxant effect seems to be slight. We have also observed the relaxant effect of eriodictyol on phorbol-12-myristate-13-acetate (PMA) (10(-7) M) induced contractions both in normal calcium (IC50 = 4.69 +/- 0.3 x 10(-5) M) and calcium-free medium (IC50 = 3.74 +/- 0.4 x 10(-5) M). Finally we studied the effects on protein kinase C (PKC) activity. This flavonoid did not show any activity. These results suggest that the vasodilator effect of eriodictyol in rat thoracic aorta could be partially related to the inhibition of calcium influx or other enzymatic protein subsequent to activation of PKC related to the activation of contractile proteins like myosin light chain kinase (MLCK).     

Different mechanisms involved in the vasorelaxant effect of flavonoids isolated from Satureja obovata

The inhibitory effects of naringenin, eriodictyol, and luteolin (10(-5) and 5 x 10(-5) M), previously isolated from Satureja obovata subsp. obovata var. valentina (Lamiaceae), on rat thoracic aorta were investigated. Flavonoids at the two concentrations assayed (10(-5) and 5 x 10(-5) M) showed different smooth muscle relaxant behaviour in the three phases involved in the noradrenaline (10(-6) M)-induced contractions. The three flavonoids showed an inhibitory effect of the phasic component in order of potency: luteolin > eriodictyol > naringenin. Luteolin and eriodictyol inhibited both tonic-I and tonic-II phases associated to the inhibition of PKC and calcium influx, respectively, whereas naringenin only inhibited the tonic-I phase associated to inhibition of PKC.     

Barriers to follow‐up of abnormal screening mammograms among low‐income minority women

Objective. To describe factors related to compliance diagnostic follow‐up among minority women of low socioeconomic status with abnormal screening mammograms.

Methods. A retrospective cross‐sectional survey using a structured telephone interview. Three cancer screening clinics at an urban inner‐city public hospital. All women with abnormal screening mammograms between September 1990 and January 1992 were eligible; women were interviewed in August 1992. Abnormal mammograms were those requiring specific, non‐routine clinical follow‐up; non‐compliance was defined as delayed follow‐up (four to six months after the date of the mammogram), or no follow‐up at the time of interview (more than 6 months after abnormal).

Results. Sixty‐two of 442 screened women had abnormal results; the overall rate of non‐compliance with follow‐up was 50%. Among the 42 (68%) women who agreed to be interviewed, non‐compliers were less likely to state that they had been told to receive follow‐up than compilers (65% versus 100%; p = 0.008). Non‐compliant women were less likely to have suspicious mammography interpretations (p = 0.05), and more likely to report barriers to follow‐up, such as cost of lost wages and medical care, system barriers, or fears, than compliant women (61.9% versus 9%, p = 0.01). There were no differences between the two groups for age, education, insurance, source of care, family history, knowledge or attitudes.

Conclusions. These preliminary results suggest that follow‐up of low income, minority women with abnormal screening mammograms could be enhanced by improved communication of results. Future studies should extend these findings with larger samples and in other settings and populations.     

Chagasic heart disease in Mexico. 1st case diagnosed by positive xenodiagnosis

We describe the first case of chronic Chagas heart disease in México, in whom the illness was corroborated by means of the "xenodiagnosis". The patient had changing bundle branch block and also A-V block that required insertion of a pacemaker. This disease is seldom seen in Mexico.     

Phytoestrogens possess a weak antioxidant activity on low density lipoprotein in contrast to the flavonoid quercetin in vitro in postmenopausal women.

BACKGROUND: Phytoestrogens are a family of plant-derived compounds with weak estrogenic and antiestrogenic properties. The antioxidant capacity of phytoestrogens has been proposed as one of the important mechanisms that explain their health benefits. OBJECTIVE: To determine the in vitro potency of three phytoestrogens, ubiquitous in food, (biochanin A, daidzein and genistein) as antioxidants of low density lipoprotein (LDL) and to compare them with the well-established antioxidant actions of estradiol and quercetin, an ubiquitous flavonoid which is found in high concentration in onions, tea and berries. METHODS: LDL was isolated by ultracentrifugation from the plasma of ten healthy postmenopausal women who were not on hormone therapy. Aliquots containing 0.5 mg of protein were incubated for 4 h with CuSO4 15 micromol/l to induce oxidative stress and with one of the five compounds studied: estradiol, quercetin, biochanin A, daidzein, and genistein, in doses of 0, 5, 15, 50, 500, 1000 and 2000 micromol/l. In addition, we studied the combined effect of estradiol 1 micromol/l plus quercetin 1 micromol/l, comparing their antioxidant action with that of each compound separately. Malonaldehyde (MDE nmol/ mg protein) was measured as a marker of LDL oxidation. RESULTS: Estradiol and quercetin induced a dose-dependent decrease in MDE concentration (p < 0.01). Comparing the areas under the curve, the antioxidant effect of quercetin was 8 times higher than the one observed with estradiol (p < 0.01). A 50% decrease in MDE was reached by quercetin at a concentration of 3.4 micromol/l, estradiol at 29 micromol/l, genistein at 280 micromol/l, biochanin at 1312 mmol/l and daidzein at 8007 mmol/l. Estradiol 1 micromol/l and quercetin 1 micromol/l did not modify MDE generation separately, but, when incubated combined, there was a significant decrease of MDE (p < 0.02). CONCLUSION: The phytoestrogens studied showed a weak antioxidant activity in vitro. The flavonoid quercetin, in contrast, showed the most potent antioxidant activity in vitro, higher than estradiol. Estradiol and quercetin showed additive antioxidant activity. We speculate that different compounds with variable antioxidant effects could amplify their antioxidant capacity when acting combined.     

Neuromagnetic alpha suppression during an auditory sternberg task. Evidence for a serial, self-terminating search of short-term memory

Reaction times (RT) during the Sternberg memory paradigm generally increase with memory set size, but do not differ for positive and negative probe stimuli. Sternberg proposed that this indicated that short-term memory (STM) scanning is both exhaustive and serial. However, this notion has received much criticism, primarily because RT must also reflect response selection factors. Magnetoencephalographic (MEG) recordings of auditory alpha-suppression have previously demonstrated that suppression duration is correlated with set size, potentially providing a physiological index of memory scanning time related specifically to sensory cortices. The current study expands earlier research into this metric by separately analyzing positive and negative probes. Thirteen normal adults participated in an auditory Sternberg paradigm. Pure tones were presented in memory set/probe combinations where the probe had a 50 percent chance of being within the memory set, and RT and accuracy were measured. Magnetic alpha-band activity (8-12 Hz) was quantified for pre- and post-stimulus regions. Although RT did not differ for positive and negative probes, alpha-suppression duration was greater for negative probes than positive ones, potentially indicating that scanning time was slightly faster in the positive condition. This may indicate that STM scanning is serial, but self-terminates when matching occurs.