Effects Of Deficiency Research Articles

PM2.5 source apportionment in Lombardy (Italy): Comparison of receptor and chemistry-transport modelling results

This work discusses the source apportionment results produced by receptor and chemistry-transport modelling for PM2.5 in Northern Italy, selected as case study due to its very critical conditions. Receptor modelling was performed using the Chemical Mass Balance model, while source oriented analysis by means of the CAMx chemistry transport model. Models shared the same source profiles, mostly based on local data. CMB showed a better reconstruction of the mass closure, while CAMx systematically underestimated cold season concentrations. Nevertheless both models provided the same source ranking at several receptors. According to CMB results, the most relevant contributions during the cold season, ranging around 10 μg m−3, were yielded by road transport, domestic heating and ammonium nitrate. CAMx provided similar results for the secondary sources, while systematically underestimated road transport and domestic heating. A similar behaviour was observed during the summer season. The main discrepancies between the models were: the questionable results from CMB at some receptors, missing the road transport contribution, clearly pointed out by CAMx/PSAT; the ability of CAMx/PSAT to apportion the contribution of sources sharing similar profiles and strongly correlated such as CI and SI vehicles, altogether recognized as traffic source by CMB; the ability of CAMx/PSAT to identify the contribution of secondary PM deriving from complex chemical transformation, such as anthropogenic and biogenic SOA. Finally, the comparison of specific source contribution pointed out that CAMx missed the reconstruction of the road transport contribution to the OC, mostly as a consequence of deficiencies in the emission inventories concerning the primary OC in the cold season and the concurrent underestimation of emissions and secondary OC formation in the warm season.

Severe vitamin D deficiency is associated with frequently observed diseases in medical inpatients

Vitamin D deficiency consequences may go beyond altered calcium homeostasis and musculoskeletal disease. Medical inpatients are often vitamin D-deficient, but little information is available about the relation of vitamin D status with extra-skeletal disorders in this population. We analysed the relationship between the concentrations of 25-hydroxyvitamin D [25(OH)D], the marker of vitamin D status, and the conditions most commonly causing admission in 115 consecutive medical inpatients. Sixty-five subjects (56.5%) had severe vitamin D deficiency [25(OH)D < 8 ng/ml]. Age (β = -0.35, p = 0.01) and hepatic disease (β = -0.21, p = 0.02) were significant correlates of 25(OH)D levels. Compared with patients with ≥ 8 ng/ml 25(OH)D, those with < 8 ng/ml 25(OH)D had significantly higher parathyroid hormone (PTH) concentrations [123 (92.7-208.2) ng/l vs. 88 (68.5-129.5) ng/l, p < 0.001], were significantly more likely to have arterial hypertension (OR 2.76, 95% CI 1.16-6.58), heart failure (HF) (OR 2.49, 95% CI 1.14-5.47), cerebrovascular disease (OR 3.23, 95% CI 1.41-7.39), and infections (OR 2.44, 95% CI 1.02-5.87), and stayed in hospital significantly longer (10 days vs. 7.5 days, p = 0.01). Only the probability of having an infection remained significantly higher in cases with severe vitamin D deficiency after adjustment for age (OR 2.41, 95% CI 1.03-5.68) and persisted after further correcting for presence of hepatic disease and PTH values (OR 2.66, 95% CI 1.03-6.88). A significant association between PTH and HF (OR 2.32, 95% CI 1.05-5.09) and length of hospitalisation (β = 0.22, p = 0.04) emerged in the fully adjusted regression models. Severe vitamin D deficiency is associated with commonly presenting extra-skeletal diseases in medical inpatients. With the exception of infections, this association is mainly driven by age. Additional studies are needed to determine whether vitamin D testing on admission may help stratifying specific categories of patients by clinical severity.

Resonance Raman spectroscopy reveals that substrate structure selectively impacts the heme-bound diatomic ligands of CYP17.

An important function of steroidogenic cytochromes P450 is the transformation of cholesterol to produce androgens, estrogens, and the corticosteroids. The activities of cytochrome P450c17 (CYP17) are essential in sex hormone biosynthesis, with severe developmental defects being a consequence of deficiency or mutations. The first reaction catalyzed by this multifunctional P450 is the 17α-hydroxylation of pregnenolone (PREG) to 17α-hydroxypregnenolone (17-OH PREG) and progesterone (PROG) to 17α-hydroxyprogesterone (17-OH PROG). The hydroxylated products then either are used for production of corticoids or undergo a second CYP17 catalyzed transformation, representing the first committed step of androgen formation. While the hydroxylation reactions are catalyzed by the well-known Compound I intermediate, the lyase reaction is believed to involve nucleophilic attack of the earlier peroxo- intermediate on the C20-carbonyl. Herein, resonance Raman (rR) spectroscopy reveals that substrate structure does not impact heme structure for this set of physiologically important substrates. On the other hand, rR spectra obtained here for the ferrous CO adducts with these four substrates show that substrates do interact differently with the Fe-C-O fragment, with large differences between the spectra obtained for the samples containing 17-OH PROG and 17-OH PREG, the latter providing evidence for the presence of two Fe-C-O conformers. Collectively, these results demonstrate that individual substrates can differentially impact the disposition of a heme-bound ligand, including dioxygen, altering the reactivity patterns in such a way as to promote preferred chemical conversions, thereby avoiding the profound functional consequences of unwanted side reactions.

Deficiency of the purine metabolic gene HPRT dysregulates microRNA-17 family cluster and guanine-based cellular functions: a role for EPAC in Lesch-Nyhan syndrome

Lesch-Nyhan syndrome (LNS) is a neurodevelopmental disorder caused by mutations in the gene encoding the purine metabolic enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). A series of motor, cognitive and neurobehavioral anomalies characterize this disease phenotype, which is still poorly understood. The clinical manifestations of this syndrome are believed to be the consequences of deficiencies in neurodevelopmental pathways that lead to disordered brain function. We have used microRNA array and gene ontology analysis to evaluate the gene expression of differentiating HPRT-deficient human neuron-like cell lines. We set out to identify dysregulated genes implicated in purine-based cellular functions. Our approach was based on the premise that HPRT deficiency affects preeminently the expression and the function of purine-based molecular complexes, such as guanine nucleotide exchange factors (GEFs) and small GTPases. We found that several microRNAs from the miR-17 family cluster and genes encoding GEF are dysregulated in HPRT deficiency. Most notably, our data show that the expression of the exchange protein activated by cAMP (EPAC) is blunted in HPRT-deficient human neuron-like cell lines and fibroblast cells from LNS patients, and is altered in the cortex, striatum and midbrain of HPRT knockout mouse. We also show a marked impairment in the activation of small GTPase RAP1 in the HPRT-deficient cells, as well as differences in cytoskeleton dynamics that lead to increased motility for HPRT-deficient neuron-like cell lines relative to control. We propose that the alterations in EPAC/RAP1 signaling and cell migration in HPRT deficiency are crucial for neuro-developmental events that may contribute to the neurological dysfunctions in LNS.

On the Performance of Management Consulting Teams

Top management consulting firms play a crucial role in today’s corporate strategic planning. In business practice, however, they are often criticized for providing inferior solutions as a consequence of deficiencies in the client-consultant interactions. This paper examines the antecedents of consulting teams’ performance to gain better insights into potential interrelations between team competences, client-consultant interaction processes, and their relations with team performance. More specifically, we assess the mediating role of consulting teams’ adaptability. The findings contribute to research on teams in organizations, and consulting teams in particular, by highlighting the important role of team adaptability to a specific, contextually embedded task and the close interaction between teams and their clients to enhance clients’ satisfaction with the services provided.

High sero-prevalence of caseous lymphadenitis identified in slaughterhouse samples as a consequence of deficiencies in sheep farm management in the state of Minas Gerais, Brazil

BackgroundCaseous lymphadenitis (CLA), caused by Corynebacterium pseudotuberculosis, is one of the most important diseases of sheep and goats, causing considerable economic losses for herd owners.ResultsWe assessed the seroprevalence of infection with C. pseudotuberculosis in 805 sheep from 23 sheep farms that supply slaughterhouses in the state of Minas Gerais; we also analyzed management practices that could be associated with CLA occurrence, used on these and nearby farms that also supplied animals to the slaughterhouse (n = 60). The serum samples for assaying CLA infection were taken at the slaughterhouse. Frequency of infection with C. pseudotuberculosis was estimated at 43.7%, and farm frequency was estimated at 100%. Management practices were analyzed through a questionnaire. All farmers (60/60) had extensive/semi-extensive rearing system; 70.0% (42/60) identified sheep individually; 11.7% (7/60) had periodical technical assistance; 41.7% (25/60) disinfected the facilities; 86.7% (52/60) used barbed wire fences and did not implement adequate CLA control measures; only 11.7% (7/60) of breeders reported vaccination against C. pseudotuberculosis; 13.3% (8/60) took note of animals with clinical signs of CLA; 1.7% (1/60) opened and sanitized abscesses, and isolated the infected animals; 10.0% (6/60) knew the zoonotic potential of this disease and 1.7% (1/60) of the farmers culled animals in case of recurrence of abscesses.ConclusionsIt can be concluded that C. pseudotuberculosis infection is widely spread in sheep flocks in Minas Gerais state in Brazil and that there is a lack of good management measures and vaccination, allowing transmission of this infectious agent throughout the production network.

Behavioral and Molecular Consequences of Deficiency of Endogenous Kynurenines in Honeybees (Apis mellifera L.)

Behavioral and histochemical studies demonstrated that endogenous tryptophan metabolites – kynurenines – play a role in the long-term retention of memory traces and the functioning of key components in the (GluR–LIMK1– F-actin) signaling cascade, which mediates these functions. Kynurenine deficiency induced by injections of allopurinol (a tryptophan oxygenase inhibitor) inhibited long-term memory, decreased the level of expression of LIMK1, and produced a paradoxical increase in the F-actin level in the cerebral ganglion in bees. These results are consistent with our previous data obtained in Drosophila with a mutation in the structural gene for tryptophan oxygenase, i.e., the vermilion mutation.

Targeted antioxidant therapies in hyperglycemia-mediated endothelial dysfunction

Although intensive glycaemic and blood pressure control have reduced the risks of micro- and macrovascular complications, diabetes remains a major cause of cardiovascular events, end-stage renal failure, blindness and neuropathy. It is therefore imperative to understand the underlying mechanisms and to establish effective treatments to prevent, retard or reverse diabetic complications. One area of increased focus is the diabetic vascular endothelium. Hyperglycaemia triggers a cascade of events, not least an increase in reactive oxygen species (ROS) leading to enhanced oxidative stress, with its negative impact on endothelial function. In this review, we explore a unifying hypothesis that increased glucose-mediated ROS leads to endothelial dysfunction as the underpinning causative event triggering accelerated micro- and macrovascular complications. In particular, the consequences of deficiencies in the antioxidant enzyme, glutathione peroxidase, on endothelial dysfunction as a trigger of diabetic micro- and macrovascular complications, will be reviewed. Furthermore, novel antioxidant therapies will be highlighted. Specifically, use of Gpx1-mimetics holds promise as a targeted antioxidant approach and an alternative adjunct therapy to reduce diabetic complications.

The Long and Short of Fertility and Longevity

Does life span extension come with a reproductive trade-off? In a recent report published in Nature, Greer et al. (2010) show that in the nematode worm C. elegans, life span extension, as a consequence of deficiencies in histone methylation, requires an intact germline and ongoing fertility.

Vitamin D insufficiency: a common and treatable problem in the Irish population

Vitamin D insufficiency is an extremely common condition particularly in the older Irish population. This is a consequence of Ireland's geographical position and climate. A recent study showed more than 75% of a cohort of older Irish females had vitamin D insufficiency. We outline the definition of vitamin D insufficiency and deficiency, its sources and metabolism as well as the clinical consequences of deficiency. We explore the current guidelines and discuss the pitfalls in the management of vitamin D replacement and in particular address recent Irish data on the feasibility and efficacy of intramuscular treatment. Vitamin D is important for calcium homeostasis and bone metabolism and reduced levels lead to osteomalacia, exacerbate osteoporosis and increase the risk of falls. Evidence is emerging that vitamin D has a role beyond musculoskeletal health and may impact on the cardiovascular and autoimmune systems, as well as the risk of malignancy.

Dietary counseling in the prevention and control of oral diseases – a review

There is a close relationship between diet, nutrition and dental health. Oral tissues like all tissues in the body are diet and nutrition-dependent. Knowledge of food sources, their properties, functions, requirements, optimal levels and consequences of deficiencies must form the basis for dietary counseling Enough is now known about the interdependence of nutrition, diet and dental diseases that dietary counseling has become a very important and integral part of dental care in developed countries. This is not surprising because oral tissues like all tissues in the body are diet and nutrition – dependent. In this paper, the scientific basis for dietary counseling in oral health and the role of sucrose in the etiology of some oral and metabolic disease has been reviewed. The importance of diet counseling and the critical elements of counseling have been outlined. It is recommended, that dietary counseling in dental diseases should be comprehensive for the whole human health and not just for any particular dental disease. Given the time consuming nature of diet counseling it is suggested, that dental practitioners make effort to regularly refer patients/clients presenting with dietrelated oral diseases to nutritionist-dietitians who have been professionally trained in the science and art of diet/nutrition counseling. In the absence of such professionals, patients/clients should as a matter of routine be referred to dental nurses and dental hygienists for nutritional counseling.Key Words: Diet, Nutrition, Oral diseases, Counseling.

Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling

Autophagy is a highly conserved process that maintains homeostasis by clearing damaged organelles and long-lived proteins. The consequences of deficiency in autophagy manifest in a variety of pathological states including neurodegenerative diseases, inflammatory disorders, and cancer. Here, we studied the role of autophagy in the homeostatic regulation of innate antiviral defense. Single-stranded RNA viruses are recognized by the members of the RIG-I-like receptors (RLRs) in the cytosol. RLRs signal through IPS-1, resulting in the production of the key antiviral cytokines, type I IFNs. Autophagy-defective Atg5(-/-) cells exhibited enhanced RLR signaling, increased IFN secretion, and resistance to infection by vesicular stomatitis virus. In the absence of autophagy, cells accumulated dysfunctional mitochondria, as well as mitochondria-associated IPS-1. Reactive oxygen species (ROS) associated with the dysfunctional mitochondria were largely responsible for the enhanced RLR signaling in Atg5(-/-) cells, as antioxidant treatment blocked the excess RLR signaling. In addition, autophagy-independent increase in mitochondrial ROS by treatment of cells with rotenone was sufficient to amplify RLR signaling in WT cells. These data indicate that autophagy contributes to homeostatic regulation of innate antiviral defense through the clearance of dysfunctional mitochondria, and revealed that ROS associated with mitochondria play a key role in potentiating RLR signaling.

Pre-clinical activity of the PARP inhibitor AZD2281 in human breast cancer cell lines and in combination with DNA damaging agents.

Abstract Abstract #1038 Background: Deficiencies in DNA repair mechanisms have been associated with breast cancer. AZD2281, a potent, oral, PARP inhibitor has been shown to have clinical activity in patients with BRCA mutant breast cancers. Laboratory studies have suggested that non-BRCA mutant breast cancers may also be sensitive to PARP inhibition in tumors as a consequence of deficiencies in other homologous recombination (HR) repair components. Using a large panel of human breast cancer cell lines we tested the hypotheses that (1) there may be a subset of non-BRCA mutant breast cancers that are sensitive to single-agent AZD2281 and (2) AZD2281 would potentiate the cytotoxic effects of the DNA damaging agent cisplatin. Methods: 43 human cell lines representing known molecular subgroups of breast cancer (i.e. ER+, HER2 amplified, “triple-negative”), and 3 immortalized breast lines were treated in duplicate in adherent plates with AZD2281 using two-fold dilutions over 6 concentrations for 6 days. Dose response curves were generated using a cell count assay to calculate the IC50 of AZD2281. In addition, a subset of cell lines that grow under anchorage independent conditions were grown in triplicate in the presence and absence of 1 µM AZD2281 in soft agar for at least 3 weeks and growth inhibition was calculated as per cent of untreated control. Cell lines (both sensitive and resistant to single agent AZD2281) were also evaluated in combination with cisplatin in a cell count assay to assess the interaction between the two agents.&amp;#x2028; Results: The majority of breast cancer cell lines evaluated in the short term 2-D growth assay did not show significant growth inhibition (IC50 &amp;lt; 1 µM) following AZD2281 treatment, including a known BRCA mutant cell line, suggesting this assay may not be ideal for determining sensitivity to AZD2281. However, in the longer term anchorage independent clonogenic assay, approximately half of the cell lines evaluated demonstrated an IC50 &amp;lt; 1 µM. Of note, the majority of the cell lines representing a “triple-negative” phenotype appeared sensitive to AZD2281 in this assay. In addition, pre-treatment with AZD2281 prior to cisplatin, potentiated the growth inhibition seen with cisplatin in both AZD2281 sensitive and resistant cell lines. Additional studies evaluating predictive markers other than BRCA status are ongoing. Conclusion: The PARP inhibitor AZD2281 has significant pre-clinical activity in human breast cancer cell lines. In a clonogenic assay, cell lines representing the “triple negative” subtype were especially sensitive to AZD2281 supporting clinical development in this population, regardless of BRCA status. In addition, these pre-clinical data support the hypothesis that PARP inhibition may potentiate the effects of chemotherapy induced DNA damage and provide further rationale for clinical development. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1038.

Assessing the Indoor Environment of Primary Schools in the Southwest of Turkey

In developing countries, the effects of natural disasters and accidents are often more serious in those buildings with a high number of occupants as a consequence of deficiencies in the built design and insufficiency of inspections. We have surveyed a number of state primary schools to examine their interior physical environment with respect to school safety and security. We studied all the 37 state primary schools located in the Isparta region of Turkey during the period between March and May of 2002. The results showed that all the schools of the region had a number of inadequacies because they had not been adequately adapted to comply with existing standards. Most of the schools had over-large class sizes, had one or more classrooms in an underground floor (proscribed in areas where there is a high risk of earthquakes), inadequate security and safety precautions to ensure pupil safety and had no proper air ventilation within the classrooms. The survey showed that local and central official bodies must reinforce the need for standards and ensure the implementation of high standards in the schools to ensure the pupil health, safety and security, and that they should work together with parents and other local associations.

Cell context-specific effects of the beta-tubulin glycylation domain on assembly and size of microtubular organelles.

Tubulin glycylation is a posttranslational modification found in cells with cilia or flagella. The ciliate Tetrahymena has glycylation on ciliary and cortical microtubules. We showed previously that mutating three glycylation sites on beta-tubulin produces immotile 9 + 0 axonemes and inhibits cytokinesis. Here, we use an inducible glycylation domain mutation and epitope tagging to evaluate the potential of glycylation-deficient tubulin for assembly and maintenance of microtubular systems. In axonemes, the major defects, including lack of the central pair, occurred during assembly, and newly made cilia were abnormally short. The glycylation domain also was required for maintenance of the length of already assembled cilia. In contrast to the aberrant assembly of cilia, several types of cortical organelles showed an abnormally high number of microtubules in the same mutant cells. Thus, the consequences of deficiency in tubulin glycylation are organelle type specific and lead to either insufficient assembly (cilia) or excessive assembly (basal bodies and cortical microtubules). We suggest that the diverse functions of the beta-tubulin glycylation domain are executed by spatially restricted microtubule-associated proteins.

Glucose transporters: structure, function and consequences of deficiency.

There are two mechanisms for glucose transport across cell membranes. In the intestine and renal proximal tubule, glucose is transported against a concentration gradient by a secondary active transport mechanism in which glucose is cotransported with sodium ions. In all other cells, glucose transport is mediated by one or more of the members of the closely related GLUT family of glucose transporters. The pattern of expression of the GLUT transporters in different tissues is related to the different roles of glucose metabolism in different tissues. Primary defects in glucose transport all appear to be extremely rare and not all possible deficiencies have been identified. Deficiency of the secondary active sodium/glucose transporters result in glucose/galactose malabsorption or congenital renal glycosuria. GLUT1 deficiency produces a seizure disorder with low glucose concentration in cerebrospinal fluid and GLUT2 deficiency is the basis of the Fanconi-Bickel syndrome, which resembles type I glycogen storage disease.

Cation accumulation by winter wheat forage: II. Correlation with multi‐ion model

Abstract The effects of three ratios of Ca/(Ca + K) and three rates of NO3‐N on ion ratios in plants grown in soil and nutrient culture are reported. Plant uptake parameters, based on nutrient culture studies, together with soil chemical parameters, were used in a multiple‐ion uptake model to calculate the cumulative, uptake of individual ions. These calculated uptakes were then used to derive relevant ratios for comparison with those measured in plants grown in soil in a growth chamber. The results illustrate that the ionic ratios based on the model are well correlated with the measured plant ratios. Regressions of plant ratios on model ratios were calculated; the intercepts were not zero and the slopes were not one. The discrepancies between measured and model ratios were probably a consequence of deficiencies in the model and unmeasured plant uptake parameters. The results illustrate that the model is a useful way to summarize data and to generate hypotheses.

Hereditary elliptocytosis, spherocytosis and related disorders: Consequences of a deficiency or a mutation of membrane skeletal proteins

The membrane skeleton, a protein lattice that laminates the internal side of the red cell membrane, contains four major proteins: spectrin, actin, protein 4.1 and ankyrin. By mass, the most abundant of these proteins is spectrin, a fibre-like protein composed of two chains, α and β, which are twisted along each other into a heterodimer. At their head region, spectrin heterodimers are assembled into tetramers. At their distal end, these tetramers are interconnected into a two dimensional network by their linkage to oligomers of actin. This interaction is greatly strengthened by protein 4.1. The skeleton is attached to the membrane by ankyrin, a protein that connects the spectrin β chain to the major transmembrane protein band 3, the anion channel protein. Additional attachment sites are those of protein 4.1 with several glycoproteins, namely glycophorin A and C, as well as direct interactions between spectrin, protein 4.1 and the negatively charged lipids of the inner membrane lipid bilayer. Hereditary spherocytosis, elliptocytosis and pyropoikilocytosis represent a group of disorders that are due to deficiency or dysfunction of one of the membrane skeletal proteins (Fig. 1). Known deficiency states include that of spectrin, ankyrin and protein 4.1. Severe spectrin and ankyrin deficiencies (with decrease in spectrin and ankyrin contents to about 50% of the normal amount) are both rare disorders associated with severe autosomal recessive hereditary spherocytosis. On the other hand, mild spectrin deficiency is found in the majority of patients with autosomal dominant spherocytosis in which the degree of spectrin deficiency correlates with the clinical severity of the disease. Protein 4.1 deficiency, in contrast, is associated with hereditary elliptocytosis, which in certain populations constitutes about 20% of all such patients. Known skeletal protein dysfunctions include mutants of both α and β spectrin that involve the spectrin heterodimer self-association site. These are clinically expressed as hereditary elliptocytosis (HE) and a closely related disorder, hereditary pyropoikilocytosis (HPP). At the level of protein function, this defect can be detected by analysis of the content of spectrin dimers and tetramers in 0°C low ionic strength extracts of red cell membranes. Their structural identification is accomplished by limited proteolytic digestion of spectrin followed by two-dimensional tryptic peptide mapping. This approach consistently reveals the presence of abnormal peptides, which are derived from the αI domain, (the self-association site of the α spectrin). The severity of HE and HPP depends on the amounts of mutant spectrin in the cells and the severity of the spectrin self-association defect. In addition, subjects with HPP, but not HE, are also partially deficient (up to 30%) in spectrin. In this paper, an hypothesis is advanced that the loss of surface area in hereditary spherocytosis is a consequence of partial deficiency of spectrin. In contrast, poikilocytosis, which is characteristically present in more severe forms of HE or HPP, is principally due to a loss of two dimensional integrity of membrane skeleton.

A clinician and a scientist look at acquired a validation of immunology's theoretical foundation

Although clinical immunology has contributed greatly to diagnostic precision and laboratory science, it has not yet made any truly significant inroads into treatment which is, after all, the bottom line. We still administer nonspecific and highly toxic drugs like corticosteroids and immunosuppressives. We employ methods like lymphoplasmaphoresis or total lymphoid irradiation, understanding very little about why they work or if they work. Transfer factor, thymic hormones, interferon and the like have been around for over ten years but are still largely experimental. Clinical immunologists are treating cancer and autoimmune disorders as we did a decade ago. It is my thesis that acquired immunodeficiency syndrome, popularly known as AIDS, indirectly offers a challenge and hope that this situation might change in this decade. For one thing, AIDS has made the general public more aware of clinical immunology. Secondly, this condition with complex and multifactorial etiology seems to validate the theoretical foundation upon which the clinical science of immunology is based. In AIDS, environmental, genetic, viral and sociological factors interact in an unfortunate combination that results in devastating immunodeficiency, high risk for opportunistic infections, and susceptibility for Kaposi 's sarcoma in almost epidemic proportions (Table I). Clinical immunology is undergoing a transition from a descriptive science to one devoted more to modulation and restoration. We recognize that even immunologically hyperactive states like autoimmunity arise as a consequence of deficiencies in regulatory cells, factors and function. Stimulated by enormous technological advances and supported by industry as well as by government and academia, we have launched an effort to develop new drugs and biological agents that could lead to therapeutic advances in autoimmunity and cancer. Nowhere are these new modalities more critically needed than today in major US cities where the mortality from AIDS is approximately 50%. More individuals have died from AIDS than from Legionnaire 's disease and toxic-shock syndrome combined. The basic facts of AIDS are as well known to the general public as they are to physicians. There have been over 1 200 known cases since the first reports appeared two years ago '-3. 87 % of cases occur in male homosexuals, spreading anxieties, fears and new psychological problems in this population. Other groups at risk are intravenous-drug users, hemophiliacs maintained on lyophilized factor-VIII concentrate prepared from pooled plasma, Haitians (Haiti is a vacation spot for homosexuals), and women and children in contact with these populations 4. 5% of cases do not belong to any definable ' at risk' category. The disease, probably the greatest medical mystery of the modern era, is almost certainly associated with a transmissible agent, perhaps a defective virus, possibly a mutated cytomegalovirus or hepatitis B virus (Table II). There is a prodromal syndrome characterized by fever, malaise, diarrhea, weight loss and generalized lymphadenopathy. The progression from this stage to the fullblown syndrome is not a frequent event. Pneumocystis carinii pneumonia is the most common infection, but unusual viruses (cytomegalovirus [CMV], Epstein-Barr virus [EBV], herpes simplex virus), fungi (Candida, Aspergillus, CO~ptococcus), protozoa (Toxoplasma) O r bacteria (Mycobacterium tuberculosis) may establish themselves in the immunocompromised and thus defenseless host 5. There is a marked impairment of cell-mediated immunity and T-cell effector functions leading to lymphopenia, skin anergy and impaired proliferative response to antigens, alloantigens and mitogens 6'7. Helper T cells are greatly decreased with a variable effect on suppressor T cells. They are often normal but can be increased, reducing the helper:suppressor (T4:T8) ratio. P r o duction of interleukin-2 (IL-2) and )'-interferon is diminished, but thymosin a, levels are elevated in patients with the prodrome 6. Natural killer cell and antibodydependent killer-cell activities are impaired. B-cell function is generally spared and some few instances of autoimmune thrombocytopenic purpura have been reported s,9.

Boron Deficiency in a Southern Pine Nursery

Abstract Boron deficiency in seedling loblolly (Pinus taeda L.) and slash pine (Pinus elliotti Engelm.) in a northern Florida nursery was diagnosed by: (1) characteristic damage to shoot tips and buds, including necrosis of only part of the terminal; and (2) boron concentrations as low as only 1.9 ppm (dry weight) in affected tissues. Soil and soil-management features associated with deficiency include extremely low silt and clay contents, organic matter levels of 1 percent or less, lack of boron addition, and high calcium irrigation water leading to soil reactions above pH 6 by late summer. Consequences of deficiency were not limited to the nursery. Damaged seedlings that survived outplanting developed into bushy plants incapable of normal height growth in the first year or two.