Immunological responses in patients with tuberculosis and in vivo effects of acetyl-L-carnitine oral administration

Tuberculosis (TBC) is characterized by a complex immune response which parallels the clinical course of the disease. In this respect, acquired resistance, delayed hypersensitivity reaction and anergy are the main types of immune reactivity to mycobacterial antigens. In view of the presence of nonspecific and specific immune deficits in TBC patients, a clinical trial was carried out in a group of 20 individuals with active pulmonary TBC by oral administration of acetyl-L-carnitine (ALC). This drug, which has been shown to possess immunomodulating activities, was able to upregulate the T-dependent antibacterial activity in TBC patients after 30 days' treatment, while the same activity decreased in patients receiving placebo only. On the other hand, ALC did not modify serum levels of tumour necrosis factor-alpha, in the same individuals. This cytokine plays a detrimental rather than beneficial role in TBC pathogenesis. In the light of these data, ALC seems to be a powerful immunomodulator in the course of Mycobacterium tuberculosis infection and other mycobacteriosis.     

Circadian Rhythm of Cardiac Output, Peripheral Vascular Resistance, and Related Variables by a Beat-to-Beat Monitoring

This study aimed to explore the 24-h patterns of stroke volume, cardiac output, and peripheral vascular resistance along with other correlated variables, such as left ventricular ejection time, ejection velocity index, thoracic fluid index, heart rate, and blood pressure. The study was performed on 12 clinically healthy subjects by means of a noninvasive beat-to-beat monitoring using the thoracic electric bioimpedance technique associated with the automated sphygmomano-metric recording. Time data series were analyzed by means of chronobiological procedures. The results documented the occurrence of a circadian rhythm for all the variables investigated, giving relevance to the beat-to-beat bioperiodicity of cardiac output and peripheral vascular resistance. Temporal quantification of the investigated variables may be useful for a better insight of the chronophysiology of the cardiovascular apparatus.     

Fibronectin turnover in human mesangial cell cultures as affected by Adriamycin

Fibronectin (FN) turnover and turnover changes induced by the anticancer drug Adriamycin (ADR) were measured in human mesangial cells (HMC) in vitro. HMC cultures synthesize cellular FN (2.2+-0.3% of totalprotein synthesis; n = 12) which is secreted and incorporated into a fibrillar extracellular matrix (ECM). A 24 hr incubation of HMC with ADR (0.5–5 g/ml) resulted in an accumulation of FN in the culture medium, with a maximum increase following 5 pglml(7.3+-2.3pg/cell vs. controls: 4.4+-1.9pg/cell; n= 10). Correspondingly, radioactively labeled immunoprecipitable FN was increased in a dosage-dependent manner in the culture medium up to 50% vs. controls. The incorporation of radioactively labeled FN into ECM was significantly increased following 2 g ADR/ml. In accordance, immunofZuorescence staining revealed an expansion ofpericellular FNfibers in cultures exposed to 2 g ADR/ml. Concomitant with the accumulation of extracelhlar FN, radioactively labeled FN in the cells was reduced by 22%. Qualitative characterization of FN patterns revealed a diminished number of degradation products in the culture medium ofADR-treated HMC. These data suggest thatADR interferes with the turnover of FN secreted by HMC in vitro in such a way that FN accumulates extracellularly. This in turn leads to a reduced FN synthesis. These findings are compatible with a loss of urinary FN degradation products accompanying the onset ofproteinuria in ADR-treated rats.Abbreviations ADR adriamycin - BSA bovine serum albumin - DTT dithiothreitol - ECM extracellular matrix - EDTA ethylenediamine tetraacetic acid disodium salt - ELISA enzyme-linked immunosorbent assay - FCS fetal calf serum - FITC fluorescein isothiocyanate - FN fibronectin - HMC human mesangial cell - PBS phosphate buffered saline - PMSF phenylmethylsulfonyl fluoride - SDS sodium dodecyl sulfate - SDS-PAGE SDS-polyacrylamide gel electrophoresis     

Odontocete spatial patterns and temporal drivers of detection at sites in the Hawaiian islands

Successful conservation and management of marine top predators rely on detailed documentation of spatiotemporal behavior. For cetacean species, this information is key to defining stocks, habitat use, and mitigating harmful interactions. Research focused on this goal is employing methodologies such as visual observations, tag data, and passive acoustic monitoring (PAM) data. However, many studies are temporally limited or focus on only one or few species. In this study, we make use of an existing long-term (2009–2019), labeled PAM data set to examine spatiotemporal patterning of at least 10 odontocete (toothed whale) species in the Hawaiian Islands using compositional analyses and modeling techniques. Species composition differs among considered sites, and this difference is robust to seasonal movement patterns. Temporally, hour of day was the most significant predictor of detection across species and sites, followed by season, though patterns differed among species. We describe long-term trends in species detection at one site and note that they are markedly similar for many species. These trends may be related to long-term, underlying oceanographic cycles that will be the focus of future study. We demonstrate the variability of temporal patterns even at relatively close sites, which may imply that wide-ranging models of species presence are missing key fine-scale movement patterns. Documented seasonal differences in detection also highlights the importance of considering season in survey design both regionally and elsewhere. We emphasize the utility of long-term, continuous monitoring in highlighting temporal patterns that may relate to underlying climatic states and help us predict responses to climate change. We conclude that long-term PAM records are a valuable resource for documenting spatiotemporal patterns and can contribute many insights into the lives of top predators, even in highly studied regions such as the Hawaiian Islands.     

Psychosocial Concerns and Health-Compromising Behaviors among Overweight and Nonoverweight Adolescents

Objective: To compare weight-specific and global psychosocial concerns and health-compromising behaviors among overweight and nonoverweight youth across gender and ethnicity. Methods: A cross-sectional school-based survey of 31,122 adolescents in grades 7 to 12. Based on self-reported heights and weights, respondents were categorized as nonoverweight (body mass index (BMI) <85th percentile), moderately overweight (85th percenile <BMI <95th percentile), or severely overweight (BMI >95th percentile). Results: Global psychosocial concerns, such as emotional well-being, suicidal ideation, future job concerns, and peer concerns, did not differ greatly between nonoverweight, moderately overweight, and severely overweight adolescents. Substance abuse behaviors were equally or less prevalent among the overweight group. Overweight girls were significantly less likely to consume alcohol, whereas overweight boys were at lower risk for marijuana use. In contrast, overweight youth were more likely to perceive their health as only fair or poor and were more likely to express weight-specific concerns and engage in behaviors such as chronic dieting and binge eating than nonoverweight youth. Overweight American Indian girls perceived their physical health more positively than nonoverweight American Indian girls. Strong associations were found between overweight status and chronic dieting among African American boys and girls. Conclusions: Nutritional counseling and educational programs need to address the weight-specific concerns and behaviors of overweight adolescents. However, assumptions regarding global psychosocial concerns and health-compromising behaviors among overweight adolescents of different genders and ethnicities should be avoided. These broad issues need to be explored in more depth at both the research and intervention levels.     

A High-Resolution Interval Map of the q21 Region of the Human X Chromosome

In a previous study, we have developed a panel of chromosomal rearrangements for the physical mapping of the q13-q21 region of the human X chromosome (Philippe et al., Genomics 17: 147-152, 1993). Here, we report the physical localization of 36 additional polymorphic markers by polymerase chain reaction analysis. The high density of chromosomal breakpoints in Xq21 allows us to map 58 DNA loci in 22 intervals. As a result, this segment of the X chromosome is saturated with approximately three sequence tagged sites per megabase of DNA, which will facilitate the construction of a YAC contig of this region.     

The effect of monochromatic radiation in the range 350 to 750 nm on the carotenogenesis in Verticillium agaricinum

An action spectrum for carotenogenesis in V. agaricinum has maxima at 395, 433, 660 and 737 nm. In a previous study it had been shown that a light-minus-dark difference spectrum of a crude extract from V. agaricinum had maxima at 390 and 420 nm, and furthermore a red, far-red interaction suggesting phytochrome involvement has been proposed. All these data suggest that there may be at least two photoreceptor systems operating in the photoinduction process here; one for the near-ultraviolet (UV-A)-mediated carotenogenesis, presumably a novel pigment, and the other for the red, far-red region, most likely phytochrome.     

Sterols from three Lactarius species

The sterol composition of three fungi was determined. Ergosterol is the major sterol, accompanied by other closely related sterols.     

Inhibition of human seminal fluid and Leishmania donovani phosphatases by molybdate heteropolyanions

Inhibition of a tartrate-resistant acid phosphatase (ACP) from Leishmania donovani and the tartrate-sensitive ACP from human seminal fluid (prostatic ACP) was examined using a series of 13 molybdate-containing heteropolyanions. The heteropolyanions were divided into four groups based on the number of molybdenum atoms they contain: Group I, Mo4; Group II, Mo6-8; Group III, Mo12; Group IV, Mo18. Two of the four groups, those consisting of compounds that contain either an Mo4 unit or an Mo18 unit with a heteroatom in the central cavity, were potent inhibitors and exhibited the highest degree of selectivity against the leishmanial and seminal fluid ACPs. The inhibition of prostatic ACP by complex E2 could be completely reversed by dialysis. Little inhibition of the acid phosphatase, beta-glucuronidase, or alpha-mannosidase from human spleen was observed with complexes B' and E2. For the seminal fluid phosphatase, the Ki values obtained with arsenate and vanadate depended markedly on pH, suggesting that, unlike most other phosphatases, the conformation of the inhibitor binding site on human seminal fluid ACP is pH-dependent. Results of competition experiments performed with various inhibitor pairs indicated that complex D2 binds to the active site of prostatic ACP while complex M binds at some site on the enzyme that affects the active site. Binding of complex M also modifies the affinity of the enzyme for other inhibitors such as vanadate. The potency of several heteropolyanion complexes and their selective inhibition of pathophysiologically significant acid phosphatases indicate that these compounds may have value as tools for study of the structure and function of this class of enzyme and perhaps in the therapy of human disease.     

Psychophysical studies of the itch sensation and itchy skin ("alloknesis") produced by intracutaneous injection of histamine.

Psychophysical measurements of itch and itchy skin ("alloknesis"--itch produced by innocuous mechanical stimulation) were obtained in human volunteers following intracutaneous or subcutaneous injections of histamine or papain into the volar forearm. Histamine and papain were given in doses of 0.1, 1, or 10 micrograms in 10 microliters of saline. The effects of the depth of injection and of skin temperature on the latency, magnitude, and duration of itch were examined. Also, dose-response functions were obtained for the area of alloknesis produced by intracutaneous injections of histamine. Finally, the neural mechanisms underlying the spread of alloknesis were investigated via local anesthesia of the skin. Intracutaneous and subcutaneous injections of histamine, but not papain, produced a sensation of itch without pain. The latency of itch was shorter after an intracutanous than after a subcutaneous injection of histamine. The mean latencies of itch produced by a 1-microgram dose were 9.5 and 23.0 sec for intracutaneous and subcutaneous injections, respectively. No differences were observed in the magnitude or duration of itch. Similarly, the latency of itch was increased when the skin temperature at injection site was lowered to 15 degrees C, whereas the magnitude and duration of itch were unaffected. Intracutaneous and subcutaneous injections of histamine produced similar areas of alloknesis. However, the magnitude and duration of alloknesis were dependent on dose. The mean maximum areas of alloknesis produced by intracutaneous injections of 0.1, 1, and 10 micrograms of histamine were 28.3, 47.2, and 43.8 cm2, respectively. Alloknesis was present at 2 min after injection, increased to a maximum area without 10 min, and then gradually decreased during the next 25-40 min.(ABSTRACT TRUNCATED AT 250 WORDS)