The relationship of human platelet density to platelet age: platelet population labeling by monoamine oxidase inhibition

The relationship between platelet density and platelet age appears to vary between species with relatively few labeling studies in humans reported. In this study, irreversible monoamine oxidase (MAO) inhibitors were used to biochemically label the circulating platelet population in 15 humans. Platelet samples were then isolated during the 15 days after drug ingestion. The platelets were separated by density on continuous linear Percoll gradients and the density distributions were divided into five fractions containing approximately equal numbers of platelets. Baseline MAO activity was strongly correlated with platelet density. Twenty-four hours after a single dose of tranylcypromine, platelet MAO activities in the density subpopulations were reduced to 14% to 17% of the baseline values. During the first five days after inhibition, the rates of recovery of MAO activity (percentage per day) were inversely proportional to platelet density. The recovery rates in the two most dense fractions were initially slow but increased after five days. Percentage recovery of MAO activity in the least dense fraction was significantly greater than the percentage recovery in the most dense fraction on days 2, 3, 5, and 8 (P less than .01, sign test). These results support the hypothesis that normal human platelets show a small increase in density with age, but they do not exclude the additional possibility that human platelet lifespan is positively correlated with platelet density.     

The risk of nursing home admission in three communities

Beginning in 1982, the 3-year incidence of nursing home admission was determined for community-dwelling residents aged 65 and over in East Boston, Massachusetts (4%); New Haven, Connecticut (9%); and Iowa and Washington Counties, Iowa (12%). A common methodology was used to collect baseline risk factor and follow-up data on nursing home admissions among persons in each community as part of the National Institute on Aging's Established Populations for Epidemiologic Studies of the Elderly. A multivariate logistic regression model of baseline risk factors that included the participant's age, race, sex, history of prior admission, ADL limitations, cognitive function, living arrangements, and level of income predicted 80% of the users in each community.     

Slow moving proteinase. Isolation, characterization, and immunohistochemical localization in gastric mucosa

Human gastric mucosa contains three immunochemically distinguishable aspartic proteinases, pepsinogen I (pepsinogen A), pepsinogen II (pepsinogen C, progastricsin), and a nonpepsinogen proteinase also termed slow moving proteinase (SMP). The properties of SMP, and in particular its relationship to another aspartic proteinase, cathepsin D, were examined in this study. Slow moving proteinase and cathepsin D were isolated, respectively, from gastric mucosa and human spleen. Antiserum specific to each proteinase was prepared in rabbits. Rabbit anti-SMP did not recognize cathepsin D, and conversely, anticathepsin D did not react with SMP. Immunohistochemical studies localized SMP to surface epithelial cells in both the fundic and pyloric gland areas of the stomach. In contrast, cathepsin D was found mainly in mononuclear cells in the lamina propria and in parietal cells. Slow moving proteinase exhibited considerably lower Km values for its interaction with two chromogenic substrates than did cathepsin D. An even greater distinction between the two enzymes was found with the protein inhibitor from Ascaris lumbricoides; the activity of SMP was inhibited very strongly, whereas that of cathepsin D was not affected. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis under denaturing conditions, SMP consisted of two subunits with apparent molecular weights of 42,500 and 41,000. The last two properties characterize a less-well-known aspartic proteinase, cathepsin E. We conclude that SMP is not cathepsin D, but that it may be cathepsin E.     

Successful treatment of fulminant Clostridioides difficile infection with emergent fecal microbiota transplantation in a patient with acute myeloid leukemia and prolonged,severe neutropenia

We present a patient with acute myeloid leukemia and prolonged, severe neutropenia who developed fulminant Clostridioides difficile infection refractory to medical therapy and was high‐risk for surgical intervention. He was treated with fecal microbiota transplantation (FMT) for life‐saving cure. The patient had subsequent clinical improvement, however, developed multidrug‐resistant Pseudomonas aeruginosa bacteremia 2 days post‐procedure. We describe subsequent investigation of this event that found this bacteremia was not related to the donor stool administered during FMT. This case adds to the literature that FMT could be considered in heavily immunocompromised patients with fulminant Clostridioides difficile infection where maximal medical therapy has been ineffective and surgery may carry an excessively high mortality risk.     

Epistasis effects of dopamine genes on interval timing and reward magnitude in humans

We tested human participants on a modified peak procedure in order to investigate the relation between interval timing and reward processing, and examine the interaction of this relation with three different dopamine-related gene polymorphisms. These gene polymorphisms affected the expression of catechol-o-methyltransferase, which catabolizes synaptic dopamine primarily in the prefrontal cortex (COMT Val158Met polymorphism), D2 dopamine receptors primarily in the striatum (DRD2/ANKK1-Taq1a polymorphism), and dopamine transporters, which clear synaptic dopamine in the striatum (DAT 3′ VNTR variant). The inclusion of these polymorphisms allowed us to investigate dissociable aspects of the dopamine system and their interaction with reward magnitude manipulations in shaping timed behavior. These genes were chosen for their roles in reward processing and cortico-striatal information processing that have been implicated for interval timing. Consistent with recent animal studies, human participants initiated their timed anticipatory responding earlier when expecting a larger reward in the absence of any changes in the timing of response termination or perceived time. This effect however was specific to two out of four evaluated COMT and DRD2 polymorphism combinations that lead to high prefrontal dopamine coupled with high D2 density and low prefrontal dopamine coupled with low D2 density. Larger rewards also decreased timing precision indices, some of which interacted with the COMT polymorphism. Furthermore, the COMT polymorphism that leads to higher prefrontal dopamine resulted in weaker manifestation of memory variability (relative to threshold variability) in timed behavior. There was no effect of DAT polymorphisms on any of the core behavioral measures. These results suggest that the reward modulates decision thresholds rather than clock speed, and that these effects are specific to COMT and DRD2 epistasis effects that presumably constitute a balanced prefrontal and striatal dopamine transmission.