Miracle-dz/UniFAR-FTUs huggingface dataset:
Roles of relSpn in stringent response, global regulation and virulence of serotype 2 Streptococcus pneumoniae D39

RelA/SpoT homologue (RSH) proteins have (p)ppGpp synthetase and hydrolase activities that mediate major global responses to nutrient limitation and other stresses. RSH proteins are conserved in most bacteria and play diverse roles in bacterial pathogenesis. We report here that the RSH protein of Streptococcus pneumoniae, RelSpn, can be deleted and is the primary source of (p)ppGpp synthesis in virulent strain D39 under some conditions. A D39 ΔrelSpn mutant grew well in complex medium, but did not grow in chemically defined medium unless supplemented with the metals copper and manganese. Transcriptome analysis of D39 rel+Spn and ΔrelSpn strains treated with mupirocin revealed relSpn‐independent (translation stress), relSpn‐dependent (stringent response) and ΔrelSpn‐dependent changes, suggesting that relSpn and (p)ppGpp amount play wide‐ranging homeostatic roles in pneumococcal physiology, besides adjusting macromolecular synthesis and transport in response to nutrient availability. Notably, the relSpn‐dependent response included significant upregulation of the ply operon encoding pneumolysin toxin, whereas the ΔrelSpn‐dependent response affected expression linked to the VicRK and CiaRH two‐component systems. Finally, a D39 ΔrelSpn mutant was severely attenuated and displayed a significantly altered course of disease progression in a mouse model of infection, which was restored to normal by an ectopic copy of rel+Spn.
Intranasal infection of beige mice with Mycobacterium avium complex: role of neutrophils and natural killer cells

Beige mice show increased susceptibility to intranasal infection with organisms of the Mycobacterium avium complex (MAC) compared with their immunocompetent congenics, C57BL/6 mice. This increased susceptibility was clear 2 weeks postinfection, before the activation of the specific immune response. T lymphocytes from 4-week infected beige mice, cultured in vitro, produced amounts of gamma interferon similar to those found in cells from C57BL/6 mice. Macrophage activation, as judged by NO production and lysis of the macrophage target P815, occurred in the lungs of beige mice. Despite the inability of bone marrow-derived NK cells from beige mice to lyse NK-susceptible YAC-1 cells, their gamma interferon production was normal. Monoclonal antibody to NK1.1 was used to deplete C57BL/10 mice of lytic activity against YAC-1 cells without exacerbating infection between 2 and 6 weeks of observation, making it unlikely that any deficiency in NK cells was the cause of susceptibility in beige mice. There was a striking influx of neutrophils in the lungs of beige mice compared with C57BL/6. More than half of the MAC organisms appeared associated with the neutrophils of beige mice, while in C57BL/6 mice, most MAC organisms were associated with cells of macrophage/monocyte morphology. Injection of monoclonal antibody specific for neutrophils failed to eliminate those cells from the lungs of beige mice. However, in C57BL/6 mice, neutrophil numbers were reduced by 95% without exacerbating the infection. We conclude that, although neutrophils are not essential to the relative resistance of C57BL/6 mice, the known deficiencies in both neutrophils and macrophages account for the susceptibility of beige mice.
Effects of nerve impulses on threshold of frog sciatic nerve fibres.

1. The firing thresholds of single myelinated fibres of frog sciatic nerves were monitored as a function of impulse activity in the fibre. The threshold was given by the number of coulombs in current pulses that excited a particular fibre half the time when delivered to the whole nerve. Threshold was tracked by a device that incrementally decreased the number of coulombs in the current pulse whenever the fibre responded and increased the pulse if it did not respond. 2. There was a pattern to the after‐oscillations of threshold following activity. The fibres were briefly refractory, transiently superexcitable for about 1‐1.5 sec and then entered a phase of raised threshold or 'depression' that lasted for many minutes. 3. Activity produced little change in the threshold curve during the refractory period. Strong depressions following prolonged activity prevented the threshold from returning to the base‐line level within the time associated with the refractory period for the same fibre at rest. 4. After an impulse, superexcitability reached a maximum within 7‐20 msec. This peak was larger as the number of impulses in a preceding burst increased and as the intervals between the impulses became briefer. Each successive impulse of a burst contributed less to the growth of superexcitability, and after the burst had 6‐10 impulses additional impulses contributed nothing. 5. The depression phase was marked by the interaction between build‐up, which depended on the activity rate, and recovery, which required as long as an hour or more for the threshold to be completely restored to resting level. These two mechanisms, one causing build‐up and the other recovery, led to formation of dynamic equilibria. The threshold level at equilibrium increased monotonically with the activity rate. 6. The processes associated with superexcitability interact with those producing depression. In active fibres showing raised thresholds, impulses are followed by a relative superexcitability that persists for at least as long as an absolute superexcitability (with threshold below the resting level) can be measured in the same fibre at rest. 7. The duration of the superexcitable phase interpreted as a relative change in excitability was roughly the same regardless of the level of depression. 8. The magnitude of the oscillation in threshold was give to ten times larger than the grey region (the range of stimuli for which response is probabilistic). It is concluded that at regions of low conduction safety such as axonal branches, where weak forces can influence whether an impulse will pass, such pronounced and long‐lasting after‐effects of firing can be expected to modulate conduction of nerve impulses.
High prevalence of low HDL-cholesterol in a pan-European survey of 8545 dyslipidaemic patients

ABSTRACT Objective: Low HDL-cholesterol is a strong independent cardiovascular risk factor recognized as a therapeutic target in recent guidelines. The Pan-European Survey on HDL-cholesterol collected data on plasma lipid profiles from 8545 dyslipidaemic patients in the care of 1339 specialist physicians in 11 European countries. The main objective was to obtain a reliable estimation of the prevalence of low HDL (< 1.03 mmol/L [< 40 mg/dL] in men; < 1.29 mmol/L [< 50 mg/dL] in women). Research design and methods: Eligible patients were aged ≥ 18 years and had received diet and exercise plus pharmacologic lipid-modifying treatment for ≥ 3 months, or had serum cholesterol ≥ 5.18 mmol/L (≥ 200 mg/dL) and/or serum triglycerides ≥ 2.03 mmol/L (≥ 180 mg/dL) despite ≥ 3 months of diet and exercise. Results: The survey population was overweight (mean body mass index 29.0 kg/m2), with a high prevalence of sedentary lifestyle (68%), type 2 diabetes (45%), hypertension (72%) and coronary heart disease (45%). Lipid-modifying treatment, received by 85% of patients, included lifestyle modification (85%) and/or lipid-lowering drugs (85% received a statin). The prevalence of low HDL-cholesterol despite lipid-modifying treatment was 40% (women) and 33% (men). Very low HDL-cholesterol (< 0.90 mmol/L [< 35 mg/dL]) occurred in 14% of treated patients, with similar prevalence in the subgroup of patients not receiving such treatment. Hypertriglyceridaemia (> 1.69 mmol/L [> 150 mg/dL]) occurred in 57% of men not under lipid-modifying treatment and in 47% of men receiving such treatment; corresponding values in women were 48% and 43%. Both low HDL-cholesterol and hypertriglyceridaemia occurred in 26% of men and 27% of women who were not receiving lipid-modifying treatment and in 21% of men and 25% of women receiving lipid-modifying treatment. Conclusions: Low HDL-cholesterol and hypertriglyceridaemia are, therefore, common among European patients treated for dyslipidaemia. Clearly, physicians need to focus more of their attention on this major risk factor and to consider adequate treatment when indicated.
Stimulation of the middle meningeal artery leads to Fos expression in the trigeminocervical nucleus: a comparative study of monkey and cat

The pain of a migraine attack is often described as unilateral, with a throbbing or pulsating quality. The middle meningeal artery (MMA) is the largest artery supplying the dura mater, is paired, and pain‐producing in humans. This artery, or its branches, and other large intracranial extracerebral vessels have been implicated in the pathophysiology of migraine by theories suggesting neurogenic inflammation or cranial vasodilatation, or both, as explanations for the pain of migraine. Having previously studied in detail the distribution of the second order neurons that are involved in the transmission of nociceptive signals from intracranial venous sinuses, we sought to compare the distribution of second order neurons from a pain‐producing intracranial artery in both monkey and cat. By electrically stimulating the middle meningeal artery in these species and using immunohistochemical detection of the proto‐oncogene Fos as a marker of neuronal activation, we have mapped the sites of the central trigeminal neurons which may be involved in transmission of nociception from intracranial extracerebral arteries. Ten cats and 3 monkeys were anaesthetised with α‐chloralose and the middle meningeal artery was isolated following a temporal craniotomy. The animals were maintained under stable anaesthesia for 24 h to allow Fos expression due to the initial surgery to dissipate. Following the rest period, the vessel was carefully lifted onto hook electrodes, and then left alone in control animals (cat n = 3), or stimulated (cat n = 6, monkey n = 3). Stimulation of the left middle meningeal artery evoked Fos expression in the trigeminocervical nucleus, consisting of the dorsal horn of the caudal medulla and upper 2 divisions of the cervical spinal cord, on both the ipsilateral and contralateral sides. Cats had larger amounts of Fos expressed on the ipsilateral than on the contralateral side. Fos expression in the caudal nucleus tractus solitarius and its caudal extension in lamina X of the spinal cord was seen bilaterally in response to middle meningeal artery stimulation. This study demonstrates a comparable anatomical distribution of Fos activation between cat and monkey and, when compared with previous studies, between this arterial structure and the superior sagittal sinus. These data add to the overall picture of the trigeminovascular innervation of the intracranial pain‐producing vessels showing marked anatomical overlap which is consistent with the often poorly localised pain of migraine.
A probe for intracerebral aromatic amino‐acid decarboxylase activity: Distribution and kinetics of [18F]6‐fluoro‐L‐m‐tyrosine in the human brain

Positron tomography, using [18F]6‐fluoro‐L‐dopa as a tracer, has been used for the study of Parkinson's disease. Unfortunately, the analysis of data obtained with this agent is bedeviled because it readily forms labeled methylated metabolites that enter the brain. We have evaluated [18F]6‐fluoro‐L‐m‐tyrosine (FmT) as an alternative tracer to study intracerebral dopamine metabolism with positron tomography. Imaging studies in humans showed specific accumulation of this tracer in the dopamine‐rich striatal regions. Reduced striatal uptake of the tracer was demonstrated in a patient suffering from Parkinson's disease. Increased retention of the tracer was demonstrated in a subject pretreated with the peripheral decarboxylase inhibitor carbidopa. Analysis of plasma samples for labeled metabolites of FmT revealed no methylated metabolites. Results of compartmental analysis showed that a twocompartment three rate constant model described adequately the time course of radioactivity in the striatum after an injection of FmT. decarboxylation rate constant (k21) was found to be 0.0108 min−1. Because the peripheral metabolism of FmT is simpler than that of [18F]6‐fluoro‐L‐dopa, we propose FmT as a superior agent with which to study intracerebral dopamine metabolism in health and disease in humans.
Placental transport of low molecular weight heparin in the pregnant sheep

Summary. Standard heparin, an effective treatment for antepartum thromboembolic disease, is thought to be safe for the fetus since it does not cross the placenta. Recently, a number of low molecular weight heparins have been prepared which have been shown to produce less bleeding than standard heparin for an equivalent antithrombotic effect in experimental animals. These observations suggest that the low molecular weight heparins may also provide superior antithrombotic therapy in antepartum thromboembolic disease. However, it is not known whether the low molecular weight heparins cross the placenta. To determine this, we examined the pharmacokinetics of 125I‐labelled standard heparin and a low molecular weight heparin, and their anticoagulant effects in mother and fetus, using a pregnant sheep model. Catheters were inserted into maternal and fetal femoral arteries at 108–119 d gestation (term: 147 d). 1–3 days later the mothers were given a bolus i.v. injection of 5000 anti‐Xa units of 125I‐labelled standard heparin or low molecular weight heparin, CY 222. Nine serial blood samples were collected over 4 h from both mother and fetus for measurements of radioactivity, anti‐Xa activity (chromogenic) and activated partial thromboplastin times. When therapeutic levels of standard and CY 222 heparins were achieved in the mother, there was no detectable radioactivity or anticoagulant effect in the fetus. We conclude that standard heparin and the low molecular weight CY 222 do not cross the placenta in the pregnant sheep.
Vestibular Schwannoma: An Understanding of Growth Should Influence Management Decisions

Background Treatments for vestibular schwannomas include surgical removal and radiotherapy. Observation is a reasonable alternative, given the slow growth of these tumors. The goal of this study was to determine the 5-year no-growth rate in patients managed initially by observation in attempts to define indications for treatment. Study Design Retrospective chart analysis of prospectively collected patient database. Methods Patients with unilateral vestibular schwannomas who presented in the last 10 years were reviewed. Those managed initially by observation were reviewed. At least 2 consecutive imaging studies were required. The following information was recorded from the charts: age, sex, tumor size at presentation and subsequent follow-up sessions, treatment in the event of growth, and time interval between presentation and last imaging available. The institutional ethics committee approved the study. Results One hundred ten patients were included. There were 65 male patients and 45 female patients. The mean age was 62.4 years (range, 32-91 yr). The mean follow-up was 31.4 months (range, 6-156 mo). Twenty-three patients demonstrated evidence of growth, with an overall 5-year no-growth rate of 70.6%. Despite growth, the 5-year no-intervention rate was 81.3%. Interestingly, 11 patients (10%) demonstrated tumor regression. Patients with intracanalicular tumors had a 5-year no-growth rate of 89.8% compared with 73.9% and 45.2% for Grade I and Grade II or larger tumors, respectively. The difference between intracanalicular and Grade II or larger tumors was statistically significant (p = 0.0196). Conclusion Our data suggest that treatment can be delayed in a large proportion of vestibular schwannoma patients and that this is particularly true in patients with small tumors. Despite growth, only a small percentage of patients require intervention. Thus, we recommend a period of observation to determine the need for treatment in patients without indications for urgent intervention.
Survival of Airborne MS2 Bacteriophage Generated from Human Saliva, Artificial Saliva, and Cell Culture Medium

ABSTRACT Laboratory studies of virus aerosols have been criticized for generating airborne viruses from artificial nebulizer suspensions (e.g., cell culture media), which do not mimic the natural release of viruses (e.g., from human saliva). The objectives of this study were to determine the effect of human saliva on the infectivity and survival of airborne virus and to compare it with those of artificial saliva and cell culture medium. A stock of MS2 bacteriophage was diluted in one of three nebulizer suspensions, aerosolized, size selected (100 to 450 nm) using a differential mobility analyzer, and collected onto gelatin filters. Uranine was used as a particle tracer. The resulting particle size distribution was measured using a scanning mobility particle sizer. The amounts of infectious virus, total virus, and fluorescence in the collected samples were determined by infectivity assays, quantitative reverse transcription-PCR (RT-PCR), and spectrofluorometry, respectively. For all nebulizer suspensions, the virus content generally followed a particle volume distribution rather than a number distribution. The survival of airborne MS2 was independent of particle size but was strongly affected by the type of nebulizer suspension. Human saliva was found to be much less protective than cell culture medium (i.e., 3% tryptic soy broth) and artificial saliva. These results indicate the need for caution when extrapolating laboratory results, which often use artificial nebulizer suspensions. To better assess the risk of airborne transmission of viral diseases in real-life situations, the use of natural suspensions such as saliva or respiratory mucus is recommended.
Estimating body surface area from mass and height: Theory and the formula of Du Bois and Du Bois

Background: Body surface areas are usually estimated by means of a formula due in its general form to Du Bois and Du Bois (1916), i.e. area = C × massa × heightb, where C, a and b are empirical constants. Its physical basis is unknown. Aim: The present study aimed to explain this formula, correct some errors in the associated literature and provide a clear basis for future developments. Subjects and methods: Use is made of published data, but arguments are largely based on mathematics and modelling. Results: A more fundamental formula is as follows: area = α(mass × height)1/2 + β(mass/height), where α and β are constants. For realistic values of mass and height the two equations are numerically equivalent. For individuals, β cannot be negative and b cannot exceed a, but, as regression parameters, these conditions may not be satisfied. This could be due to systematic or statistical relationships between individual values of α or β and the ratio height3/mass. Values of α, β, C, a and b are calculated for some published data. Conclusions: The original type of formula suffices for practical purposes, but the new one is better in analytical contexts when other terms, e.g. for body shape, are to be incorporated.
Effect of culture conditions on synthesis of L-asparaginase by Escherichia coli A-1

The nutritional requirements and culture conditions affecting biosynthesis of L-asparaginase in a mutant of Escherichia coli HAP designated strain A-1 were studied. Asparaginase activity was increased by the addition of L-glutamic acid, L-glutamine, or commercial-grade monosodium glutamate. The rate of enzyme synthesis was dependent on the interaction between the pH of the culture and the amount of oxygen dissolved in the medium. A critical oxygen transfer rate essential for asparaginase formation was identified, and a fermentation procedure is described in which enzyme synthesis is controlled by aeration rate. Enhancement of L-asparaginase activity by monosodium glutamate was inhibited by the presence of glucose, culture pH, chloramphenicol, and oxygen dissolved in the fermentation medium.
Changes in expression of voltage‐gated potassium channels in dorsal root ganglion neurons following axotomy

Several families of voltage‐gated potassium channels (Kv), including a spectrum of subtypes, are involved in regulating and modifying the integration and transmission of electrical signals in the nervous system. However, the specific patterns of Kv expression in normal or injured dorsal root ganglion (DRG) neurons have not been studied. Previous studies have examined the expression of voltage‐gated sodium channels in DRG neurons, and also the selective up‐ and downregulation of several of these channels following axonal injury to the DRG neurons. In the present study, we used immunocytochemical methods to investigate the expression of Kv channels (Kv1.1, 1.2, 1.3, 1.4, 1.5, 1.6, and 2.1) in DRG cells cultured from control and axotomized adult rats. Kv1.2 and 2.1 immunoreactivity in DRG neurons showed large decreases following axotomy, whereas Kv1.1 and 1.3 showed smaller decreases. Kv1.4 and 1.6 immunostaining were not altered by axotomy, and Kv1.5 immunoreactivity was low in both control and axotomized DRG neurons. These results provide molecular correlates for the expression of multiple K+ currents in normal DRG neurons and indicate that, in relation to changes in sodium channel expression, there are decreases in specific potassium channels following axotomy in these cells. The alterations in K+ and Na+ channel expression following axonal injury may lead to changes in electrical excitability of the DRG neurons, and might contribute to chronic pain syndromes. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 502–507, 1999.
IL‐10 up‐regulates nitric oxide (NO) synthesis by lipopolysaccharide (LPS)‐activated macrophages: improved control of Trypanosoma cruzi infection

We examined the effects of IL‐10 on tumour necrosis factor‐alpha (TNF‐α) and NO production by LPS‐activated macrophages and on the ability of these cells to control Trypanosoma cruzi infection. We first observed that the addition of rIL‐10 to macrophages of the J774 cell line decreased their synthesis of TNF‐α but increased their release of NO in a dose‐dependent manner. In parallel, treatment of J774 cells with rIL‐10 resulted in a better control of T. cruzi infection involving up‐regulation of NO synthesis, as it was not observed in presence of N‐nitro‐ L‐arginine methyl ester ( L‐NAME), a competitive inhibitor of NO synthase. The enhancing effect of rIL‐10 on NO production was not observed on peritoneal macrophages from wild‐type C57Bl/6 mice, but well on macrophages from IL‐10 knock‐out mice. The control of NO production by endogenous IL‐10 was confirmed by the demonstration that neutralization of IL‐10 secreted by LPS‐activated macrophages from wild‐type mice inhibited their production of NO and, in parallel, their ability to control T. cruzi infection. Taken together, these data demonstrate that both exogenous and endogenous IL‐10 up‐regulate the production of NO by LPS‐activated macrophages and improve thereby their ability to clear T. cruzi infection.