Immunology

A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in immunology.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:From oligonucleotide shapes to genomic SELEX: Novel biological regulatory loops

The SELEX method and oligonucleotide combinatorial chemistry discovery process yields high-affinity/high-specificity ligands for virtually any molecular target. Typically, the enormous starting libraries used in the SELEX process contain 10¹⁴–10¹⁵ sequences. We now ask if the smaller sequences, complexity of extant organisms, and evolutionary history provide useful interactions between oligonucleotides and at least some unexpected targets. That is, do organisms contain a robust “linkage map” between their oligonucleotides and proteins and/or small molecules that enriches life?     

Improved intracranial lesion characterization by tissue segmentation based on a 3D feature map

Our aim was to develop an accurate multispectral tissue segmentation method based on 3D feature maps. We utilized proton density (PD), T₂-weighted fast spin-echo (FSE), and T₁-weighted spin-echo images as inputs for segmentation. Phantom constructs, cadaver brains, an animal brain tumor model and both normal human brains and those from patients with either multiple sclerosis (MS) or primary brain tumors were analyzed with this technique. Initially, misregistration, RF inhomogeneity and image noise problems were addressed. Next, a qualified observer identified samples representing the tissues of interest. Finally, k-nearest neighbor algorithm (k-NN) was utilized to create a stack of color-coded segmented images. The inclusion of T₁ based images, as a third input, produced significant improvement in the delineation of tissues. In MS, our 3D technique was found to be far superior to that based on any combination of 2D feature maps (P < 0.001). We identified at least two distinctly different classes of lesions within the same MS plaque, representing different stages of the disease process. Further, we obtained the regional distribution of MS lesion burden and followed its changes over time. Neuropsychological aberrations were the clinical counterpart of the structural changes detected in segmentation. We could also delineate the margins of benign brain tumors. In malignant tumors, up to four abnormal tissues were identified: 1) a solid tumor core, 2) a cystic component, 3) edema in the white matter, and 4) areas of necrosis and hemorrhage. Subsequent neurosurgical exploration confirmed the distribution of tissues as predicted by this analysis.     

Ventilatory effects of dexmedetomidine, atipamezole, and isoflurane in dogs.

Dexmedetomidine (DMED) is a novel alpha 2 adrenergic agonist that has been shown to have potent analgesic and anesthetic sparing effects. This study was designed to investigate the effects of DMED, both alone and combined with isoflurane, on resting ventilation, the hypercapnic response, and the hypoxic response in dogs. When given alone, 1 microgram/kg decreased resting ventilation by 22% but at larger doses (10, 20, and 100 micrograms/kg) resting ventilation increased, doubling at 100 micrograms/kg. Doses of 10 micrograms/kg and greater caused a maximum depression of 60% in the slope of the hypercapnic response, but no dose had a significant effect on the hypoxic ventilatory response. A dose of 3 micrograms/kg of DMED reduced isoflurane MAC from 1.3% to 0.37%, and the ventilatory effects of this 1 MAC combination were intermediate between the awake values and those of isoflurane-anesthetized (1.3%) dogs. Atipamezole is a specific centrally acting alpha 2 receptor antagonist and when given with DMED in isoflurane-anesthetized dogs prevented the ventilatory depression. However, atipamezole alone also ventilatory stimulating effects, which may indicate tonic alpha 2 adrenergic activity. The ventilatory depression caused by DMED, either alone or combined with isoflurane, at doses that significantly reduce anesthetic requirements are relatively mild.     

The Organization of the Venous Spaces of the Cavernous Sinus

The study of the venous channels in the cavernous sinus in 48 sphenoid bones was performed. Thirty-eight bones were electrolyticly decalcified, subsequently embedded in gelatin, and cut in 1 mm thick slices. Microdissection of the other ten specimens complemented the analysis. Every specimen had the venous structure arranged as a plexus, however, although the channels were variable in number, form, and diameter, the two sides were quite symmetrical. Channels of smaller diameter predominated anteriorly. There was no demonstrable muscular layer in these vessels; the endothelial lining was easily visualized. Fatty tissue separated the venous channels from each other and from arteries and nerves. The distance from the carotid artery and the lateral wall increased anteriorly, but there were significant veins between these two structures in only 35% of the cases. In about one third of specimens the oculomotor nerve was placed over the carotid artery. The abducens nerve was found to be intimately related to the lateral wall without any venous channels between them in 92% of the specimens.     

Action of beer and its ingredients on gastric acid secretion and release of gastrin in humans

The intragastric action of beer and its known ingredients before and after fermentation on gastric acid secretion and release of gastrin was studied in healthy humans. None of 11 tested ingredients of fermented beer (2 x 500 mL, pH 5.5, given either alone or in combination) or hop extract had any significant effect. Finished beer (6 weeks old) and new beer were potent stimuli of acid output, causing 93% and 76% of the incremental maximal acid output in response to pentagastrin (6 micrograms/kg SC), respectively. Before the addition of yeast, preproducts of beer were considerably less potent. Thus, first and finished wort caused only a minor acid response which was 48% and 46% of maximal acid output. Foreign fermentation in first and finished wort is presumably the reason for the stimulatory action because glucose solutions in concentrations (11.5% wt/vol) seen in wort did not stimulate acid secretion. However, glucose solutions to which yeast was added, resulting in fermentation, were as potent stimuli of acid secretion as beer. Lyophilization of beer at pH 11.0 and dialysis (cutoff mol wt, 1000) removed the stimulatory substances. The plasma gastrin responses paralleled the gastric acid response to the different stimulants. It was concluded that (a) the addition of yeast to finished wort and the following alcoholic fermentation are the essential steps for the stimulatory action of beer on gastric acid secretion and release of gastrin; (b) carbohydrate metabolites with a molecular weight of less than 1000 are the acid-stimulatory agents in fermented beer; and (c) gastrin is the mediator of the stimulation of acid secretion because all substances that had a potent acid-stimulatory action also were potent stimuli of gastrin release.     

Ancillary Community Pharmacy Services Provided to Older People in A Largely Rural and Ethnically Diverse Region: A Survey of Consumers in West Texas

Little is known about the quality of pharmacy services provided to the rural elderly population. This exploratory study examines rural/urban and ethnic differences in perceived access to ancillary pharmacy services among elderly people. Two telephone surveys were conducted using directory listings in West Texas to generate a longitudinal sample. Persons aged 65 years and older who were not cognitively impaired were asked to complete the survey. The number of participants in both rounds of the survey was 3,689. Seven ancillary pharmacy services were examined: delivery of medications, medication counseling, written medication information, blood pressure monitoring, blood glucose monitoring, osteoporosis screening, and immunization. The sample was stratified by county of residence (urban, rural, or frontier) and racial/ethnic background. Chi-square tests were performed to detect rural/urban and racial/ethnic differences in access to the seven ancillary services. The association between proficiency in English and access to the services was also examined. Rural residents were more likely than urban residents to report that their pharmacies provide delivery of medications, medication counseling, and immunization services, but they were less likely than their urban counterparts to report that their pharmacies provide blood pressure monitoring. Access to ancillary pharmacy services was reported as poorer by older Hispanic people compared with non-Hispanics. Deficiency in English was significantly related to inequality in reported access to ancillary pharmacy services. It is essential to consider the special needs of rural and Hispanic elderly people to ensure equitable access to ancillary pharmacy services.