Use of Mono Mac 6 human monocytic cell line and J774 murine macrophage cell line in parallel antimycobacterial drug studies

The Mono Mac 6 (MM6) human monocytic cell line was evaluated with the established J774 murine macrophage cell line to ascertain its effectiveness in determining the intracellular activities of antimycobacterial drugs. Cells were infected with Mycobacterium tuberculosis H37Ra and treated with drug concentrations corresponding to the MICs, as well as to threefold higher than and threefold less than the MICs. Changes in CFU were compared after 7 days to determine significant differences between treated and nontreated groups. The results suggest that MM6 will make a useful model for testing the intracellular activities of antituberculosis drugs.     

Serotonin-4 receptor antagonists reverse cocaine-induced cardiac arrhythmia

CONTEXT: Adolescent smoking prevalence is tracked annually and has increased since 1991. In contrast, little is known about trends in smoking among college students, a group that has previously been more resistant to tobacco use than other young adults. OBJECTIVE: To examine changes in cigarette smoking among college students between 1993 and 1997 and among different types of students and colleges. DESIGN: Self-administered survey (Harvard School of Public Health College Alcohol Study). SETTING: One hundred sixteen nationally representative 4-year colleges. SUBJECTS: A total of 15103 randomly selected students in 1993 (70% response rate) and 14251 students in 1997 (60% response rate). MAIN OUTCOME MEASURES: Self-reports of cigarette smoking in the past 30 days and in the past year, age at smoking first cigarette, and number of attempts to quit. RESULTS: Over 4 years, the prevalence of current (30-day) cigarette smoking rose by 27.8%, from 22.3% to 28.5% (P<.001). The increase was observed in 99 of 116 colleges and was statistically significant (P<.05) in 27 (23%) of them. Current smoking increased across all student subgroups (defined by sex, race/ethnicity, and year in school) and in all types of colleges. Smoking is rising faster in public schools (from 22.0% to 29.3%) than in private schools (from 22.9% to 26.8%). Eleven percent of college smokers had their first cigarette and 28% began to smoke regularly at or after age 19 years, by which time most were already in college. Half of current smokers tried to quit in the previous year; 18% had made 5 or more attempts to quit. CONCLUSIONS: Cigarette use is increasing on campuses nationwide in all subgroups and types of colleges. Substantial numbers of college students are both starting to smoke regularly and trying to stop. National efforts to reduce smoking should be extended to college students.     

Rates of reinfection with Echinococcus granulosus, Taenia hydatigena, taenia ovis and other cestodes in a rural dog population in Uruguay

Forced thinking is an incompletely understood and rarely described epileptic aura. We studied three patients with forced thinking from left frontal lesions, two neoplastic and one vascular. All three experienced repetitive, intrusive thoughts at the onset of seizures. Their forced thinking was associated with the desire to vocalize, orobuccal movements, and speech arrest. The episodes occurred with other ictal manifestations and responded to antiseizure therapy. These patients suggest that epileptic forced thinking is a heterogeneous phenomenon; forced thinking from left frontal lesions is a manifestation of expressive language and is distinct from experiential thoughts arising from temporal limbic foci.     

Assessing declarative memory in schizophrenia using Wisconsin Card Sorting Test stimuli: the Paired Associate Recognition Test

The Paired Associate Recognition Test (PART) was developed to measure declarative memory using Wisconsin Card Sorting Test (WCST) stimuli, so that both tasks could be administered during functional neuroimaging to differentiate memory and executive function, and associated frontal and temporal lobe activation in schizophrenia. The current study was designed to compare PART and WCST performance in schizophrenic patients and to examine effects of medication and symptomatology. The PART, WCST, and standard declarative memory tasks were administered to 30 chronic schizophrenic patients and 30 matched healthy control subjects. Supporting task validity was the finding that patients were equally impaired on the PART and the WCST. Neuroleptics did not appear to affect performance. The effect of anticholinergic medication correlated negatively with WCST performance in a small subsample. Severity of schizophrenia-specific symptoms measured at intake on the Brief Psychiatric Rating Scale correlated negatively with performance on the WCST. These results support the application of the PART and WCST in future functional neuroimaging studies.     

The pattern of inflammation in rat sepsis due to enterotoxin-producing Staphylococcus aureus: a comparison with ischemia-reperfusion injury

Sepsis and trauma have similarities in their immunopathologic profiles. Both conditions can result in multi-system organ failure which is sometimes associated with cytokine generation and inflammatory cell activation. Furthermore, decreases in peripheral blood monocyte expression of HLA-DR have been noted in both human sepsis and trauma. However, the magnitude, onset, and time course of such stimuli are often difficult to ascertain in human studies. Thus, to study a more detailed in vivo immunologic profile in these conditions, rat models were employed. Our aim was to describe and analyze cytokine and peripheral blood immunophenotype patterns in bacterially induced rat sepsis and to compare this to rat ischemia-reperfusion injury. Sprague-Dawley rats underwent either bacterial injection with enterotoxin producing Staphylococcus aureus or hind limb ischemia/ reperfusion. Two bacterial doses which were either lethal or sublethal at 24-48 hours were utilized. Peripheral blood neutrophils and B-lymphocytes were studied for expression of beta-integrins (CD11b and CD11b/c) and I-A, respectively, using flow cytometry. Corresponding plasma levels of TNF alpha and interferon gamma were measured by ELISA. At 24 hr, a lethal bacterial lethal bacterial dose injection resulted in significantly higher levels of neutrophil CD11b/c expression (p < 0.005) compared with ischemia-reperfusion treatment. B-cell I-A expression was also higher in lethal sepsis. Gamma interferon levels were significantly higher in lethal sepsis compared with ischemia-reperfusion (p = 0.005). Studies over time showed that CD11b expression and interferon gamma were both more marked at 6 hr than at 24 hr in lethal sepsis. This pattern was not observed in sublethal sepsis or in ischemia-reperfusion. CD11b/c expression on the other hand remained elevated at comparable levels at 6 and 24 hr in lethal sepsis. B-cell I-A expression in ischemia-reperfusion and sublethal sepsis decreased at 24 hr compared with baseline. Lethal sepsis in rats injected with enterotoxin producing staphylococcus results in phasic alterations in neutrophil CD11b and plasma interferon levels prior to death. In analogy to the findings of monocyte decreases in DR expression observed in human trauma and sepsis, rat B-cell I-A expression showed decreases in sublethal sepsis as well as in ischemia-reperfusion injury. However, this was not observed in lethal sepsis. These findings have implications in understanding the immunologic/inflammatory changes observed in human sepsis and trauma.     

Effects of growth with ethanol on fermentation and membrane fluidity of Saccharomyces cerevisiae

Saccharomyces cerevisiae HSc was grown with ethanol at concentrations up to 10% (v/v). The immediate effects of additions of externally added ethanol on CO₂ production and O₂ consumption of washed organisms were studied by stopped-flow membrane inlet quadrupole mass spectrometry. Fermentative activities of organisms grown with ethanol (0–5% v/v) showed similar sensitivities to inhibition by ethanol, whereas those grown with 10% (v/v) ethanol had become protected and were markedly less sensitive. The fluidity of subcellular membrane fractions was measured by determination of the temperature dependence of the rotational order parameter of the spin label 5-doxyl stearic acid (free radical) by electron spin resonance. Mitochondria prepared from yeasts grown with 0, 7 and 9% (v/v) ethanol showed similar overall fluidity, although differences in temperature-dependent behaviour indicate altered lipid composition or lateral phase separations. On the other hand the microsomal fraction from organisms grown with 9% ethanol showed a remarkable increase in fluidity. These data suggest that the protective effects of growth with ethanol near the limit of tolerance on fermentative activities may arise from altered plasma membrane fluidity properties.     

Metabolism and biochemical effects of 3,3',4,4'-tetrachlorobiphenyl in pregnant and fetal rats

The metabolism and distribution of a single oral dose of 25 mumol 14C-labelled 3,3',4,4'-tetrachlorobiphenyl (14C-TCB) were investigated in pregnant female Wistar rats and their fetuses. TCB was administered on day 13 of gestation and the elimination was followed for 7 days. Non-pregnant rats were treated similarly for comparison. Fecal elimination of 14C-TCB derived radioactivity was significantly lower in pregnant rats than in non-pregnant rats. The major metabolite found in adult liver and plasma, placental tissue, whole fetuses and fetal plasma was 3,3',4',5-tetrachloro-4-biphenylol (4-OH-TCB). Tissue levels (liver, abdominal fat, skin, skeletal muscle, kidney and plasma) of 14C-TCB-derived radioactivity declined by 65-85% over a 7-day period following administration in the adult animals. However, 14C-TCB-derived radioactivity accumulated more than 100-fold in the fetuses over the same time period, and GC/MS analysis revealed that the fetal accumulation in radioactivity was due primarily to 4-OH-TCB, and not the parent compound. On day 20 of gestation, concentrations of 4-OH-TCB were 14 times greater in fetal plasma than maternal plasma. Treatment with 14C-TCB significantly reduced plasma thyroxine levels by at least 28% up to 7 days after administration in non-pregnant animals and up to 4 days after administration in pregnant rats (31% decrease). By 7 days after administration plasma thyroxine levels had returned to control levels in the TCB-treated pregnant rats. However, fetal plasma thyroxine levels were significantly decreased by 35% in fetuses from 14C-TCB-treated dams 7 days after TCB administration. Hepatic microsomal ethoxyresorufin-O-deethylase (EROD) activity was significantly induced in TCB-treated dams relative to controls at 4 and 7 days after administration, while no EROD activity was detected in hepatic microsomes from control or TCB treated fetal rats at day 20 of gestation. These data suggest that hydroxylated metabolites of polychlorinated biphenyls may play a role in the development toxicity of these compounds.     

Behavioral factors affecting exposure potential for household cleaning products

Variation in repeated nucleotide sequences (RNSs) at the level of entire families assayed by Southern blot hybridization is remarkably low within species and is a powerful tool for scrutinizing the origin of allopolyploid taxa. Thirty-one clones from RNSs isolated from different Triticeae genera were used to investigate the genome constitution of South American Elymus. One of these clones, pHch2, preferentially hybridized with the diploid H genome Hordeum species. Hybridization of this clone with a worldwide collection of Elymus species with known genome formulas showed that pHch2 clearly discriminates Elymus species with the H genome (StH, StHH, StStH, and StHY) from those with other genome combinations (StY, StStY, StPY, and StP). Hybridization with pHch2 indicates the presence of the H genome in all South American Elymus species except Elymus erianthus and Elymus mendocinus. Hybridization with additional clones that revealed differential restriction fragments (marker bands) for the H genome confirmed the absence of the H genome in these species. Differential restriction fragments for the Ns genome of Psathyrostachys were detected in E. erianthus and E. mendocinus and three species of Leymus. Based on genome constitution, morphology, and habitat, E. erianthus and E. mendocinus were transferred to the genus Leymus.