Gastric Emptying of Solid Meal in Male Chronic Alcoholics

Nausea and vomiting are common complaints in chronic alcoholics. Autonomic neuropathy and esophageal motor abnormalities are frequently observed in chronic alcoholics, but gastric emptying has not been studied in these patients. Gastric emptying of a solid meal was measured, using 99mTc-sulfur colloid cooked in a scrambled egg, in 10 male chronic alcoholics with upper gastrointestinal complaints of nausea and vomiting. All patients were adequately nourished, recently drinking, but just over withdrawal and free of clinical peripheral neuropathy. Gastric emptying in 10 alcoholics was similar to 5 normal controls (t 1/2 115 +/- 12 versus 107 +/- 8 min). These data suggest that upper gastrointestinal symptoms in chronic alcoholics are not related to gastric motor dysfunction.     

Evidence that large granular lymphocytes from B-CLL patients with hypogammaglobulinemia down-regulate B-cell immunoglobulin synthesis [published erratum appears in Blood 1989 Jun;73(8):2232]

B-chronic lymphocytic leukemia (CLL) patients frequently suffer from moderate to severe hypogammaglobulinemia. This complication is a serious cause of morbidity and mortality in this disorder. There is recent evidence that natural killer (NK) cells modulate B-cell immunoglobin (Ig) synthesis/secretion. The authors therefore evaluated the circulating NK cells from B-CLL patients on their ability to regulate mitogen-induced B-cell Ig synthesis. Blood, NK cells (CD16+, CD3-) from three B-CLL patients with hypogammaglobulinemia were able to clearly down-regulate the pokeweed mitogen (PWM)-induced-B-cell Ig secretion. In contrast, CD16+, CD3- cells from age-sex-matched controls or B-CLL patients with normal Ig were either nonregulatory or enhanced mitogen-induced B-cell Ig secretion. An alternative explanation for hypogammaglobulinemia in B-CLL patients is the immunomodulation of B- cell Ig production/secretion by CD16+, CD3- blood cells.     

Dracunculiasis eradication: delayed, not denied

By the end of 1998, Asia was free of dracunculiasis (Guinea worm disease), with Pakistan, India, and Yemen having interrupted transmission in 1993, 1996, and 1997, respectively. Transmission of the disease was also interrupted in Cameroon and Senegal during 1997. Chad reported only 3 cases during 1998. Dracunculiasis is now confined to only 13 countries in Africa. The overall number of cases has been reduced by more than 97% from the 3.2 million cases estimated to have occurred in 1986 to 78,557 cases reported in 1998. Because the civil war in Sudan remains the major impediment to eradication of dracunculiasis, the interim goal is to stop all transmission outside that country by the end of 2000. The most important operational need now is for national programs to improve the frequency and quality of supervision of village-based health workers in order to enhance the sensitivity of surveillance and effectiveness of case containment.     

High resolution of heterogeneity among human neutrophil granules: physical, biochemical, and ultrastructural properties of isolated fractions

Previous studies on the fractionation of human neutrophil granules have identified two major populations: myeloperoxidase (MPO)-containing azurophil, or primary, granules and MPO-deficient specific, or secondary, granules. Peripheral blood neutrophils from individual donors were lysed in sucrose-free media by either hypotonic shock or nitrogen cavitation. Using a novel two-gradient Percoll density centrifugation system, the granule-rich postnuclear supernatant was rapidly (ten minutes) and reproducibly resolved into 13 granule fractions (L1 through L8 and H1 through H5). Granule flotation and recentrifugation experiments on both continuous, self-generated and multiple-step gradients using individual and mixed isolated fractions demonstrated that the banding patterns were isopycnic and nonartifactual. Isolated granules were intact based on the findings that biochemical latency of several granule enzymes was greater than 95%, and thin-sectioned electron micrographs demonstrated intact granule profiles. Biochemical analyses of the granule marker proteins MPO, beta-glucuronidase, lysozyme, and lactoferrin indicated that a number of the fractions were related to the major azurophil and specific granule populations. Lactoferrin was found in ten of 13 fractions (L1 through L8, H1 to H2), whereas MPO was found in every fraction. Consistent with these biochemical data, all fractions exhibited varying degrees of heterogeneity based on ultrastructural morphology and cytochemistry, including diaminobenzidine (DAB) reactivity for peroxidase and periodate-thiocarbohydrazide-silver proteinate (PA-TCH-SP) staining for complex glycoconjugates. A variable but significant percentage (23% to 70%) of the granules in fractions L1 through L8 and H1 and H2 showed DAB reactivity, while about 90% of the granules in fractions H3 through H5 were peroxidase positive. These results demonstrated that DAB-reactive granules spanned the entire range of granule size and density. Ultrastructural PA-TCH-SP staining of isolated granule fractions revealed patterns similar to those of granules in intact neutrophils at different stages of development. Granules from human acute promyelocytic leukemia cells (HL-60) exhibited a surprisingly low density compared with typical azurophil granules from normal, mature neutrophils. The data suggest that both functional and maturational differences contribute to granule heterogeneity, and provide a new practical and conceptual framework for further defining the phenomenon of neutrophil granule heterogeneity.     

The Peculiar Epidemiology of Dracunculiasis in Chad

Dracunculiasis was rediscovered in Chad in 2010 after an apparent absence of 10 years. In April 2012 active village-based surveillance was initiated to determine where, when, and how transmission of the disease was occurring, and to implement interventions to interrupt it. The current epidemiologic pattern of the disease in Chad is unlike that seen previously in Chad or other endemic countries, i.e., no clustering of cases by village or association with a common water source, the average number of worms per person was small, and a large number of dogs were found to be infected. Molecular sequencing suggests these infections were all caused by Dracunculus medinensis. It appears that the infection in dogs is serving as the major driving force sustaining transmission in Chad, that an aberrant life cycle involving a paratenic host common to people and dogs is occurring, and that the cases in humans are sporadic and incidental.     

Nucleotide metabolic mismatches in mammalian hearts: implications for transplantation

Introduction

Human donor organ shortages have led surgeons and scientists to explore the use of animals as alternative organ sources. Acute thrombovascular rejection (AVR) is the main hurdle in xenotransplantation. Disparities in nucleotide metabolism in the vessels of different species may contribute significantly to the microvascular component of AVR.

Methods

We evaluated the extent of nucleotide metabolism mismatch in selected organs and endothelial cells of different mammals with particular focus on the changes in activity of ecto-5’-nucleotidase (E5’N) elicited by exposure of porcine hearts or endothelial cells to human blood (ex vivo) or human plasma (in vitro).

Results

E5’N activity in the rat heart was significantly higher than in other species. We noted a significant difference (p<0.001) in E5’N activity between human and pig endothelial cell lines. Initial pig aortic endothelial E5’N activity decreased in vitro after a three-hour exposure to human and porcine plasma while remaining constant in controls. Ex vivo perfusion with fresh human blood for four hours resulted in a significant decrease of E5’N activity in both wild type and transgenic pig hearts overexpressing human decay accelerating factor (p<0.001).

Conclusions

This study provides evidence that mismatches in basal mammalian metabolic pathways and humoral immunity interact in a xenogeneic environment. Understanding the role of nucleotide metabolism and signalling in xenotransplantation may identify new targets for genetic modifications and may lead to the development of new therapies extending graft survival.