Is Signature Size Associated With Organ Donor Designation on Driver's Licenses?

INTRODUCTION: Previous studies suggest that large signature size is associated with narcissistic characteristics. By contrast, organ donation is an indicator of altruism. Because altruism and narcissism may be viewed as opposites, we sought to determine if smaller signature size is associated with willingness to be an organ donor. METHODS: Using a cross-sectional study design, we reviewed the health records of 571 randomly selected primary care patients at a large urban safety-net medical system to obtain their demographic and medical characteristics. We also examined driver's licenses that were scanned into electronic health records as part of the patient registration process. We measured signature sizes and obtained the organ donor designation from these driver's licenses. RESULTS: Overall, 256 (45%) patients were designated as donors on their driver's licenses. Signature size averaged 113.3 mm(2) but varied greatly across patients (10th percentile 49.1 mm(2), 90th percentile 226.1 mm(2)). On multivariate analysis, donor designation was positively associated with age 18-34 years, non-black race, having private insurance, and not having any comorbid conditions. However, signature size was not associated with organ donor designation. CONCLUSIONS: Signature size is not associated with verified organ donor designation. Further work is needed to understand the relationship between personality types and willingness to be an organ donor.

The Relationship Between Verified Organ Donor Designation and Patient Demographic and Medical Characteristics.

Previous studies on the correlates of organ donation consent have focused on self-reported willingness to donate and on self-reported medical suitability to donate. However, these may be subject to social desirability bias and inaccurate assessments of medical suitability. The authors sought to overcome these limitations by directly verifying donor designation on driver's licenses and by abstracting comorbid conditions from electronic health records. Using a cross-sectional study design, they reviewed the health records of 2070 randomly selected primary care patients at a large urban safety-net medical system to obtain demographic and medical characteristics. They also examined driver's licenses that were scanned into electronic health records as part of the patient registration process for donor designation. Overall, 943 (46%) patients were designated as a donor on their driver's license. On multivariate analysis, donor designation was positively associated with age 35-54 years, female sex, nonblack race, speaking English or Spanish, being employed, having private insurance, having an income >$45 000, and having fewer comorbid conditions. These demographic and medical characteristics resulted in patient subgroups with donor designation rates ranging from 21% to 75%. In conclusion, patient characteristics are strongly related to verified donor designation. Further work should tailor organ donation efforts to specific subgroups.

Ocular oscillations on eccentric gaze.

Many normal individuals show ocular oscillations on eccentric gaze. This study was designed to investigate the effect of visual disengagement and visual feedback on the nature of these end point oscillations. Three test conditions were examined: target present, target absent and when the target position was determined by the subject's eye position via a variable feedback control system. Feedback gains (i.e. target velocity/eye velocity) ranged from 0, where the target position was decoupled from the subject's eye movements (i.e. the target is stationary on the screen), to +1.0 where the retinal image was stabilised (i.e. the target is driven by the subject's eye movements). Only subjects who exhibited sustained end-point oscillations with no latency were included in the study (n=6). Seven different oscillations including square-wave jerks were recorded in the abducting eye during eccentric gaze of a stationary target. The three most common oscillations were the jerk oscillations, with decelerating, linear or pendular slow phases. A number of additional previously unreported waveforms were also recorded. On removal of the target, the mean drift velocity of the slow phase was greatly reduced. The response to the introduction of a change in the visual feedback was specific to each subject, although in all cases, the end-point oscillations generally were of a lower velocity, and gaze was shifted by up to 8 deg in the direction of the slow phase within the first two seconds. The important role of slow eye movement control for maintaining gaze holding is discussed.

Structural and functional aspects of three major glycoproteins of the human milk fat globule membrane.

The MUC1 mucin, lactadherin, and butyrophilin are 3 major components of the human milk fat globule membrane. The mucin inhibits binding of S-fimbriated Escherichia coli to buccal epithelial cells, and lactadherin prevents symptomatic rotavirus infection in breast-fed infants. Butyrophilin has been suggested to be a structural component of the human milk fat globule (HMFG) membrane and to have receptor functions, but has no known anti-infective activity. These HMFG glycoproteins also are present in skimmed milk, possibly associated with phospholipid micelles, while mucin is also in a soluble form. Mucin and lactadherin resist digestion in the stomach of milk-fed infants, while butyrophilin is rapidly degraded. The MUC1 mucin is an extended rod-like structure forming part of the glycocalyx on the surface of many epithelial cells and membranes of milk, and may act as a decoy for binding of infective agents. The extracellular segment of butyrophilin has homology to Ig superfamily receptors and an intracellular domain with homology to developmentally regulated proteins. Lactadherin is a laterally mobile cell adhesion molecule that interacts with integrins and has a novel means of membrane-association involving specific binding to phosphatidylserine. The structural and functional aspects of these glycoproteins are discussed with regard to their role in human milk for breast-fed infants.

Waveform characteristics of manifest latent nystagmus.

PURPOSE: To examine the waveform characteristics of 37 subjects with manifest latent nystagmus (MLN) and determine the manner in which visual feedback influences the nature of the waveform. METHODS: Binocular recordings of the eye movements of all subjects were undertaken using an infrared tracking system. Subjects viewed the target binocularly and monocularly in primary gaze. The effect of visual feedback on the nature of the MLN waveform was examined by either removing the fixation target or by progressively stabilizing the target in relation to the retina. This progressive stabilization was achieved by feeding back the eye movement signal to move an otherwise stationary target. RESULTS: Four types of MLN were distinguished on the basis of the fixation characteristics seen during binocular and monocular viewing. First, under binocular viewing conditions, subjects could theoretically exhibit stable fixation (type 1 MLN). In addition, three other MLN types were recorded during binocular fixation: conjugate horizontal square-wave jerks (type 2 MLN), conjugate torsional nystagmus (type 3 MLN) and conjugate horizontal jerk MLN waveforms (type 4 MLN). Monocular viewing always gave rise to a conjugate horizontal jerk MLN waveform for each of the four types of MLN. More than 80% of the subjects exhibited either type 3 or type 4 MLN, both of which conform with previous classic descriptions of MLN. Much less common was type 2 MLN. Type 1 MLN (conventionally referred to as a latent nystagmus) appeared to be a rare occurrence. In addition to the two classic linear and decelerating MLN slow phases, four additional slow-phase shapes with either saccadic or pendular elements were recorded and described. Removing visual feedback generally reduced the mean slow-phase velocity and the number of fast phases. For each subject some variability of the slow-phase class was documented from session to session. CONCLUSIONS: Four types of MLN have been described. Their differences are based on their binocular oculomotor behavior, and it is proposed that type 1 MLN and type 4 MLN represent the absolute states and types 2 and 3 the intermediate levels of the MLN spectrum. All types of MLN appear to be strongly visually driven and are largely dependent on the attentional state of the subject and the target conditions. Six different classes of slow phase were found among the four MLN types. The introduction of visual feedback had an immediate effect on the subsequent slow phase or fast phase. It is likely that adaptation mechanisms are in play after a period of visual feedback.

The characteristics of dynamic overshoots in square-wave jerks, and in congenital and manifest latent nystagmus.

Dynamic overshoots are seen after voluntary re-fixation saccades. They are microsaccadic movements which follow primary saccades and have no delay. The purpose of this study was to examine the prevalence and metrics of the dynamic overshoots seen after involuntary saccades. Using infra-red oculography we demonstrate that dynamic overshoots are a common occurrence in physiological square-wave jerks, congenital nystagmus and manifest latent nystagmus and that these overshoots are saccadic in nature and have the same dynamic characteristics as those seen following voluntary saccades. It is therefore likely that they share common neural commands to those dynamic overshoots seen after a volitional saccade. All dynamic overshoots are postulated to be the unwanted consequence of making a saccade and are simulated in a model of fast oculomotor behaviour which is consistent with known experimental results.

Modelling of congenital nystagmus waveforms produced by saccadic system abnormalities.

Models of the mechanisms of normal eye movements are typically described in terms of the block diagrams which are used in control theory. An alternative approach to understanding the mechanisms of normal eye movements involves describing the eye movement behaviour in terms of smooth changes in state variables. The latter approach captures the burst cell firing against motor error (difference between target gaze angle and current gaze angle) phase plane behaviour which is found experimentally and facilitates the modelling of variations in burst cell behaviour. A novel explanation of several types of congenital nystagmus waveforms is given in terms of a saccadic termination abnormality.

Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector.

Pre-clinical studies in mice and haemophilic dogs have shown that introduction of an adeno-associated viral (AAV) vector encoding blood coagulation factor IX (FIX) into skeletal muscle results in sustained expression of F.IX at levels sufficient to correct the haemophilic phenotype. On the basis of these data and additional pre-clinical studies demonstrating an absence of vector-related toxicity, we initiated a clinical study of intramuscular injection of an AAV vector expressing human F.IX in adults with severe haemophilia B. The study has a dose-escalation design, and all patients have now been enrolled in the initial dose cohort (2 x 10(11) vg/kg). Assessment in the first three patients of safety and gene transfer and expression show no evidence of germline transmission of vector sequences or formation of inhibitory antibodies against F.IX. We found that the vector sequences are present in muscle by PCR and Southern-blot analyses of muscle biopsies and we demonstrated expression of F.IX by immunohistochemistry. We observed modest changes in clinical endpoints including circulating levels of F.IX and frequency of FIX protein infusion. The evidence of gene expression at low doses of vector suggests that dose calculations based on animal data may have overestimated the amount of vector required to achieve therapeutic levels in humans, and that the approach offers the possibility of converting severe haemophilia B to a milder form of the disease.

Improved muscle-derived expression of human coagulation factor IX from a skeletal actin/CMV hybrid enhancer/promoter.

Hemophilia B is caused by the absence of functional coagulation factor IX (F.IX) and represents an important model for treatment of genetic diseases by gene therapy. Recent studies have shown that intramuscular injection of an adeno-associated viral (AAV) vector into mice and hemophilia B dogs results in vector dose-dependent, long-term expression of biologically active F.IX at therapeutic levels. In this study, we demonstrate that levels of expression of approximately 300 ng/mL (6% of normal human F.IX levels) can be reached by intramuscular injection of mice using a 2- to 4-fold lower vector dose (1 x 10(11) vector genomes/mouse, injected into 4 intramuscular sites) than previously described. This was accomplished through the use of an improved expression cassette that uses the cytomegalovirus (CMV) immediate early enhancer/promoter in combination with a 1.2-kilobase portion of human skeletal actin promoter. These results correlated with enhanced levels of F.IX transcript and secreted F.IX protein in transduced murine C2C12 myotubes. Systemic F.IX expression from constructs containing the CMV enhancer/promoter alone was 120 to 200 ng/mL in mice injected with 1 x 10(11) vector genomes. Muscle-specific promoters performed poorly for F.IX transgene expression in vitro and in vivo. However, the incorporation of a sequence from the alpha-skeletal actin promoter containing at least 1 muscle-specific enhancer and 1 enhancer-like element further improved muscle-derived expression of F.IX from a CMV enhancer/promoter-driven expression cassette over previously published results. These findings will allow the design of a clinical protocol for therapeutic levels of F.IX expression with lower vector doses, thus enhancing efficacy and safety of the protocol. (Blood. 2000;95:2536-2542)

Protective function of human milk: the milk fat globule.

Human milk contains many components that protect the newborn against infection at a time when the infant's own defense mechanisms are poorly developed. Fat is one of the major nutrients in human milk. The fat is contained within milk fat globules composed of a core of triglyceride and a membrane consisting of phospholipids, cholesterol, proteins, and glycoproteins. Both the membrane and the core components can provide protection against microorganisms. The major protective membrane glycoproteins, mucin, and lactadherin are resistant to conditions in the newborn's stomach and maintain their structure and function even at low pH and in the presence of the proteolytic enzyme pepsin. The core triglycerides upon hydrolysis by digestive lipases (especially gastric lipase, which is well developed in the newborn) produce free fatty acids and monoglycerides, amphiphylic substances able to lyse enveloped viruses, bacteria, and protozoa. Therefore, in addition to its nutritional value, the fat in human milk has a major protective function.

Milk fat globule glycoproteins in human milk and in gastric aspirates of mother's milk-fed preterm infants.

Human milk fat globule (HMFG) glycoproteins can prevent infections by microorganisms in breast-fed infants; the MUC-1 mucin inhibits binding of S-fimbriated Escherichia coli to buccal mucosa, and lactadherin may prevent symptomatic rotavirus infections. In this study, the survival of these HMFG glycoproteins in the stomach of human milk-fed preterm infants (gestational age = 27.5 +/- 0.4 wk) was assessed, and levels in their mothers' milk determined, using specific RIAs. Butyrophilin, a major component of HMFG membrane that has no demonstrated antimicrobial activity, was studied for comparison. The levels of mucin, lactadherin, and butyrophilin in 41 milk samples of 20 mothers were 729 +/- 75, 93 +/- 10, and 41 +/- 3 microg/mL, respectively. Mucin and lactadherin were significantly higher in early milk samples (<15 d postpartum) than in later milk samples (15-90 d postpartum), whereas butyrophilin showed no such difference. Significant amounts of mucin and lactadherin were found in almost all gastric aspirates of human milk-fed infants, even 4 h after feeding (mucin, 270 +/- 30 microg/mL; lactadherin, 23.2 +/- 4.4 microg/mL), whereas butyrophilin was rapidly degraded in the majority of aspirates. Western blot analysis demonstrated that the immunoreactive mucin, lactadherin, and butyrophilin in the milk-fed gastric aspirates had the expected native molecular weights. Mucin and lactadherin survived at all gastric pH values, whereas butyrophilin was found only at pH > 4. Neither lactadherin nor butyrophilin were detected in gastric aspirates of formula-fed infants (gestational age = 27.8 +/- 0.5 wk), whereas the very low level of mucin (9.1 +/- 1.1 microg/mL) in this group is presumably cross-reacting gastric mucin. These results demonstrate that two HMFG glycoproteins implicated in prevention of infection, MUC-1 mucin and lactadherin, survive and maintain their integrity in the stomachs of human milk-fed preterm infants.

Role of human-milk lactadherin in protection against symptomatic rotavirus infection.

BACKGROUND: Human milk contains a 46 kDa mucin-associated glycoprotein, lactadherin, which binds specifically to rotavirus and inhibits its replication. This study tested the hypothesis that lactadherin protects against symptoms of rotavirus infection. METHODS: 200 infants in Mexico City were recruited at birth and monitored by regular stool EIA for rotavirus, serology, and recording of feeding and stool patterns. Milk samples were obtained from the mothers weekly until 4 weeks post partum then monthly. The sample taken immediately before an infant's episode of rotavirus infection was assayed for lactadherin, butyrophilin, mucin, and secretory IgA. An infection was defined as symptomatic if diarrhoea occurred in the 5 days before or after detection of the virus. FINDINGS: 31 infants developed rotavirus infection; 15 were symptomatic and 16 had no symptoms. The median concentration of lactadherin in the milk samples (obtained 4-41 days [median 13] before the infection) was 48.4 (range 5.6-180) microg/mL in the asymptomatic group and 29-2 (6.2-103-4) microg/mL in the symptomatic group. Although these medians did not differ significantly, in logistic regression analysis adjusted for age at infection and secretory IgA concentration there was a significant difference between the groups (p=0O01). No association between symptom status and concentrations of butyrophilin, mucin, or secretory IgA was found. INTERPRETATION: Protection against rotavirus by human milk is associated with the glycoprotein lactadherin. This association is independent of products of the secretory immune system.

Lactadherin (formerly BA46), a membrane-associated glycoprotein expressed in human milk and breast carcinomas, promotes Arg-Gly-Asp (RGD)-dependent cell adhesion.

Lactadherin, a major glycoprotein of the human milk fat globule membrane, is abundant in human breast milk and expressed in human breast carcinomas. Previously, we have shown that the mature protein, formerly known as BA46, has three domains: an epidermal growth factor (EGF)-like domain containing an Arg-Gly-Asp (RGD) cell adhesion sequence and C1 and C2 domains similar to those found in coagulation factors V and VIII. An alignment of lactadherin with its bovine (MGP57/53) and murine (MFG-E8) homologs shows that the RGD sequence has been conserved during evolution, suggesting that the RGD sequence is not fortuitous. We demonstrate that lactadherin purified using Triton X-114 phase partitioning promotes RGD-dependent cell attachment of green monkey kidney cells (MA104), mouse fibroblast cells (3T3-L1), and breast carcinoma cells (ELL-G). A lactadherin-specific monoclonal antibody, Mc3, inhibits attachment to purified lactadherin, suggesting that contaminants in the purification are not responsible for binding. In addition, the anti-integrin alpha(v)beta3 monoclonal antibody LM609 inhibits cell attachment of MA104 cells to lactadherin. These results demonstrate that lactadherin promotes RGD-dependent cell adhesion via integrins. Denaturation of lactadherin with heat and reducing conditions diminished cell attachment, suggesting that optimal cell attachment to RGD is dependent on the structural presentation of the sequence.