Variability in mitochondria of zebrafish photoreceptor ellipsoids.

Ultrastructural examination of photoreceptor inner segment ellipsoids in larval (4, 8, and 15 days postfertilization; dpf) and adult zebrafish identified morphologically different types of mitochondria. All photoreceptors had mitochondria of different sizes (large and small). At 4 dpf, rods had small, moderately stained electron-dense mitochondria (E-DM), and two cone types could be distinguished: (1) those with electron-lucent mitochondria (E-LM) and (2) those with mitochondria of moderate electron density. These distinctions were also apparent at later ages (8 and 15 dpf). Rods from adult fish had fewer mitochondria than their corresponding cones. The ellipsoids of some fully differentiated single and double cones contained large E-DM with few cristae; these were surrounded by small E-LM with typical internal morphology. The mitochondria within the ellipsoids of other single cones showed similar electron density. Microspectrophotometry of cone ellipsoids from adult fish indicated that the large E-DM had a small absorbance peak (∼0.03 OD units) and did not contain cytochrome-c, but crocetin, a carotenoid found in old world monkeys. Crocetin functions to prevent oxidative damage to photoreceptors, suggesting that the ellipsoid mitochondria in adult zebrafish cones protect against apoptosis and function metabolically, rather than as a light filter.

Ultrastructure of the distal retina of the adult zebrafish, Danio rerio.

The organization, morphological characteristics, and synaptic structure of photoreceptors in the adult zebrafish retina were studied using light and electron microscopy. Adult photoreceptors show a typical ordered tier arrangement with rods easily distinguished from cones based on outer segment (OS) morphology. Both rods and cones contain mitochondria within the inner segments (IS), including the large, electron-dense megamitochondria previously described (Kim et al.) Four major ultrastructural differences were observed between zebrafish rods and cones: (1) the membranes of cone lamellar disks showed a wider variety of relationships to the plasma membrane than those of rods, (2) cone pedicles typically had multiple synaptic ribbons, while rod spherules had 1-2 ribbons, (3) synaptic ribbons in rod spherules were ∼2 times longer than ribbons in cone pedicles, and (4) rod spherules had a more electron-dense cytoplasm than cone pedicles. Examination of photoreceptor terminals identified four synaptic relationships at cone pedicles: (1) invaginating contacts postsynaptic to cone ribbons forming dyad, triad, and quadrad synapses, (2) presumed gap junctions connecting adjacent postsynaptic processes invaginating into cone terminals, (3) basal junctions away from synaptic ribbons, and (4) gap junctions between adjacent photoreceptor terminals. More vitread and slightly farther removed from photoreceptor terminals, extracellular microtubule-like structures were identified in association with presumed horizontal cell processes in the OPL. These findings, the first to document the ultrastructure of the distal retina in adult zebrafish, indicate that zebrafish photoreceptors have many characteristics similar to other species, further supporting the use of zebrafish as a model for the vertebrate visual system.

A light and transmission electron microscope study of the distribution and ultrastructural features of peripheral nerve processes in the extra-retinal layers of the zebrafish eye.

The distribution and ultrastructural features of peripheral nerve processes in the extra-retinal layers of the eyes of the zebrafish, Danio rerio (Hamilton), were investigated using light and transmission electron microscopy. A comparative study of the quality of preservation provided by three different fixation procedures revealed no consistently striking general differences. However, somewhat subjectively, the fixative containing Millonig's buffer did consistently provide better fixation of myelin. Overall, nerve processes, depending on the site studied, were distributed as either (1) bundles (in the choroid near the optic nerve head and in the choroid adjacent to the limbus), (2) linear arrays (in the junction between the sclera and cartilage and in the choroid adjacent to the retina) or (3) individual units (in the choroid under the cartilage or in the sclera). Both myelinated and unmyelinated processes were identified in these locations. Myelinated processes usually contained both neurofilaments and neurotubules, but a few apparently contained only neurofilaments. Unmyelinated processes usually contained mainly neurotubules, but a few apparently contained only neurofilaments. Taken together, these findings indicate innervation of extra-retinal structures, as seen in zebrafish, is highly conserved among vertebrates, further supporting the use of zebrafish as a model for the vertebrate visual system.

A light and transmission electron microscope study of hepatic portal tracts in the rhesus monkey (Macacus rhesus).

This study reports on morphological features of hepatic portal tracts in the liver of a rhesus monkey. The light microscope shows that the number of each type of principal component comprising a portal tract varies but that there are usually one to five lymphatics, one bile ductule, one bile duct, one arteriolar and one arterial branch of the hepatic artery, and one hepatic portal vein. Bile ductules, in cross section, have 6-10 cells (mostly low pyramidal, but with a few cuboidal) bordering the lumen, an outside diameter of from about 20 to 25 microm, and a luminal diameter of from 2 to 10 microm. Bile ducts, in cross section, have more than 10 cells (about equal numbers of low pyramidal and cuboidal) bordering the lumen, an outside diameter greater than 25 microm and a luminal diameter of greater than 10 microm. The term "pyramidal" has not previously been applied to the cells of the ductules and ducts. The monkey tracts show several cytological features previously undescribed, viz., abortive cilia and basal bodies in the duct cells, abortive cilia in the ductule cells, and an occasional aggregation of ribosomes in arterial endothelial cells. They also show a major histological feature previously mentioned but not illustrated, viz., bundles of nerve processes which exhibit a preferential location, i.e., proximity to the arterioles and arteries.

Ultrastructural features of Glisson's capsule and the overlying mesothelium in rat, monkey and pike liver.

Samples from the liver of a male rat (Sprague-Dawley), a monkey (Macacus rhesus), and a longnose gar pike (Lepisosteus osseus) were studied in a transmission electron microscope to provide cytological and histological information about structures previously poorly documented in the literature. Glisson's capsule consisted of dense, irregular connective tissue of typical Type-I collagen fibrils. The capsule was formed by a single stratum of fibroblasts in the rat and in the pike, but by one or two strata of fibroblasts in the monkey. In the rat, but not in the monkey or pike, fibroblast processes interdigitated with processes from the hepatocytes. In the pike, fibroblast processes extended toward both mesothelium and hepatocytes. In some areas of the rat and pike, mesothelial cells had desmosomal connections and microvillous projections into the peritoneal cavity. Marginated heterochromatin was more abundant in the rat and monkey. The mesothelium was discontinuous in the rat and monkey but, in areas of discontinuity, the capsular surface was covered by a basal lamina, often barely perceptible beneath mesothelial cells of the rat and monkey, but prominent in the pike. In the pike, the mesothelium had numerous pinocytotic vesicles on both peritoneal and capsular surfaces.

What counts as a decision? Predictors of perceived decision making.

We examined lay perceptions of what counts as a decision. Eighty-six subjects read 10 scenarios that described clear decisions (e.g., choosing a graduate school), clear "nondecisions" (e.g., an accidental wrong turn), or ambiguous actions (e.g., eating a donut when on a diet or allowing someone else to make the decision). The subjects rated each scenario as to whether the actor had made a decision and also rated six other attributes. The scenarios were rated as clearly illustrating a decision if the actor engaged in a lot of thought and did not act reflexively. Consideration of consequences and having alternatives were moderately related to decision ratings, whereas having self-control problems and the influence of physiological drives showed little relationship with decision ratings. Thus, lay concepts of decision making differ from decision theory in that thoughtful, intentional behavior is more important in defining a decision than are decision theoretic components, such as alternatives and consequences.

Value for the future and preventive health behavior.

Many everyday decisions require trade-offs between immediate and delayed benefits. Although much research has assessed discounting of delayed outcomes by using hypothetical scenarios, little research has examined whether these discounting measures correspond to real-world behavior. Three studies examined the relationship between scenario measures of time preference and preventive health behaviors that require an upfront cost to achieve a long-term benefit. Responses to time preference scenarios showed weak or no relationship to influenza vaccination, adherence to a medication regimen to control high blood pressure, and adherence to cholesterol-lowering medication. The finding that scenario measures of time preference have surprisingly little relationship to actual behaviors exemplifying intertemporal trade-offs places limits on the applications of time preference research to the promotion of preventive health behavior.

Time preferences for the very long term.

Many important decisions concern outcomes delayed by decades or centuries. Whereas some economists have argued that inter-generational discount rates should be lower than intra-generational rates, three experiments found that inter- and intra-generational discount rates were quite similar. Experiment 1 found that discount rates for long delays (30-900 years) were lower than those for shorter delays (1-30 years) but that, holding delay constant, discount rates for outcomes occurring to future generations were similar to those for outcomes occurring to the present generation. Experiment 2 compared inter-generational discount rates for three different types of outcomes and found similar discount rates for saving lives, improving health, and financial benefits. Experiment 3 found similar inter-generational discounting of life-saving programs that benefit people close to or distant from the decision maker. These studies indicate that the discount rate applied to outcomes occurring to future generations depends on the length of the time delay but not on other factors.

A fallacy of the multiplicative QALY model for low-quality weights in students and patients judging hypothetical health states.

OBJECTIVES: In quality-adjusted life-years (QALY) models, it is customary to weigh life-years with quality of life via multiplication. As a consequence, for positive health states a longer duration has more QALYs than a shorter duration (i.e., longer is better). However, we have found that for poor health states, many prefer to live only a limited amount of time (i.e., longer is worse). Such preferences are said to be maximum endurable time (MET). In the present contribution, the following questions are asked: a) How low does the utility have to be in order for a MET to arise? and b) Do MET preferences occur when patients judge hypothetical health states? METHODS AND RESULTS: We reanalyzed data from 176 students for the hypothetical health states of "living with migraines" and "living with metastasized cancer." For utilities smaller than 0.7 (ranging from 0 to 1), the MET preference rate was larger than 50%. High MET preference rates were also found in two new studies on migraine and esophageal cancer patients, who evaluated hypothetical health states related to their disease. CONCLUSIONS: We discuss the interpretation of the MET preferences and the preference reversal phenomenon. Standard QALY models imply that longer is better. However, we find that more often, longer is worse for poorly evaluated health states. Consider the following question: are 3 years with a weight of 0.3 equally as valuable as 1 year with a weight of 0.9? Our results suggest that the 3-year period may be less valuable because for poor health, many will prefer a 1-year over a 3-year period.

YC-1, a benzyl indazole derivative, stimulates vascular cGMP and inhibits neointima formation.

The pathobiologic process of arterial stenosis following balloon angioplasty continues to be an enigmatic problem in clinical settings. This research project investigates the ability of YC-1, a benzyl indazole derivative that sensitizes sGC/cGMP, to stimulate endogenous cGMP and attenuate balloon injury-induced neointima (NI) formation in the rat carotid artery. Northern and Western blot analyses revealed enhanced acute expression of iNOS and inducible heme oxygenase (HO-1) mRNA and protein in the injured artery. The contralateral uninjured artery also demonstrated acute HO-1 mRNA and protein induction without detectable iNOS expression. Perivascular application of YC-1 immediately following injury significantly stimulated acute vessel wall cGMP compared to untreated controls. YC-1 treated sections demonstrated significant reduction in NI area (-74%), NI area/medial wall area (-72%), and NI thickness (-76%) 2 weeks post-injury. These results directly implicate YC-1 as a potent new therapeutic agent capable of reducing post-angioplasty stenosis through endogenous CO- and/or NO-mediated, cGMP-dependent processes.

Transmission electron microscope study of bacterial morphotypes on the anterior dorsal surface of human tongues.

The human tongue has been the subject of many cytological and histological studies. When a literature search disclosed no reports of the ultrastructure of the morphotypes of bacteria residing on the tongue's surface, a transmission electron microscope study of ultrathin sections of bacteria obtained by scraping eight human tongues was undertaken. The scrapings from the anterior dorsal tongue surfaces, processed conventionally for electron microscope study, revealed 33-35 different bacterial morphotypes. Several of the morphotypes were unique to a tongue. Morphotype differences were also related to donor characteristics such as smoking, tongue site, location in centrifuge pellet, diet, and medications. The predominant morphotypes were Gram-positive cocci. These preliminary findings suggest that the microbiota of the human tongue and variations in that microbiota, related to physical condition, lifestyle, medications, and dietary preferences, merit more attention from anatomists.

Physiological cyclic stretch causes cell cycle arrest in cultured vascular smooth muscle cells.

Smooth muscle cells (SMC) are the major cellular component of the blood vessel wall and are continuously exposed to cyclic stretch due to pulsatile blood flow. This study examined the effects of a physiologically relevant level of cyclic stretch on rat aortic vascular SMC proliferation. Treatment of static SMC with serum, platelet-derived growth factor, or thrombin stimulated SMC proliferation, whereas exposure of SMC to cyclic stretch blocked the proliferative effect of these growth factors. The stretch-mediated inhibition in SMC growth was not due to cell detachment or increased cell death. Flow cytometry analysis revealed that cyclic stretch increased the fraction of SMC in the G(0)/G(1) phase of the cell cycle. Stretch-inhibited G(1)/S phase transition was associated with a decrease in retinoblastoma protein phosphorylation and with a selective increase in the cyclin-dependent kinase inhibitor p21, but not p27. These results demonstrate that cyclic stretch inhibits SMC growth by blocking cell cycle progression and suggest that physiological levels of cyclic stretch contribute to vascular homeostasis by inhibiting the proliferative pathway of SMC.

Occurrence of mast cells within bundles of myelinated and unmyelinated nerves in the rat tongue.

The rat tongue has been the subject of many cytological studies, both purely descriptive and experimental. To assess the suitability of the organ for additional cytological and histological senior research thesis projects, light and transmission electron microscope studies of thin and ultrathin sections, respectively, were conducted. Several samples from the anterior dorsal surface of the tongue of a male rat (Sprague-Dawley) were processed conventionally for light and electron microscope study. About 170 sections, each approximately 1 x 1 mm in area and 1.0 microm thick, collected from 12 adjacent areas, all including the mucosa, of a tongue were studied in the light microscope. Numerous mast cells were observed scattered throughout the submucosal region, adjacent to nerve bundles, blood vessels, and skeletal muscle, and up to six bundles each consisting of many myelinated and unmyelinated nerve processes were seen per section. Single, double, and quadruple myelinated nerve processes were also seen. Several of the multiple, mixed nerve bundles contained a mast cell. Mast cells were not found within the endoneurium or perineurium of exclusively myelinated processes. Ultrathin sections adjacent to the thin sections containing mast cells within the nerve bundles were sought and studied in the transmission electron microscope to confirm the identification of these mast cells. Mast cells occur within bundles containing both myelinated and unmyelinated nerves in the rat tongue, and this is an apparently previously unreported event. Furthermore, no clear evidence has been found in the literature of such specific mast cell distribution in other parts of the animal body. Single, double, and quadruple myelinated nerve processes were noted, but none contained a mast cell.

Predictors of influenza vaccine acceptance among healthy adults.

BACKGROUND: Previous studies investigating predictors of influenza vaccine acceptance have focused on high-risk patients or health care workers. Few studies have examined flu shot acceptance among healthy adults in workplace settings, even though influenza vaccine is recommended for this group as well. METHODS: Two studies investigated predictors of flu vaccine acceptance in workplace samples of healthy adults. In the first study, 79 university employees were interviewed, while in the second, 435 corporate employees completed a questionnaire. RESULTS: In the first study, flu shot acceptance was predicted by perceived effectiveness of the vaccine (r = 0.36), perceived likelihood of vaccine side effects (r = -0.32), and having received the shot in the previous year (r = 0.25). In the second study, flu shot acceptance was again predicted by perceived effectiveness (r = 0.49), likelihood of side effects (r = -0.31), and previous flu shot (r = 0.66) and was also related to older age (r = 0.10) and to predicted percentage of co-workers who also received the shot (r = 0.24). CONCLUSIONS: The current studies indicate that predictors of vaccine acceptance among healthy adults are similar to those identified in studies of high-risk patient populations and health care workers.

A multi-attribute model of prostate cancer patient's preferences for health states.

Multi-attribute utility theory (MAUT) provides a way to model decisions involving trade-offs among different aspects or goals of a problem. We used MAUT to model prostate cancer patients' preferences for their own health state and we compared this model to patients' global judgments of health state utility. 57 patients with prostate cancer (mean age = 70) at two Chicago Veterans Administration health clinics were asked to evaluate health states described in terms of five health attributes affected by prostate cancer: pain, mood, sexual function, bladder and bowel function, and fatigue and energy. Each attribute had three levels that were used to form three clinically realistic health state descriptions (A = high, B = moderate, C = low). A fourth personalized health description (P) matched the patient's current health. We first measured patients' preferences using time trade-off (TTO) judgments for the three health states (A, B, and C) and for their own current health state (P). The TTO for the patient's own health state (P) was standardized by comparing it to TTO judgments for states A and C. We next constructed a multi-attribute model using the relative importance of the five attributes. The MAU scores were moderately correlated with the TTO preference judgments for the personalized state (Pearson r = 0.38, N = 57, p < 0.01). Thus, patients' preference judgments are moderately consistent and systematic. MAUT appears to be a potentially feasible method for evaluating preferences of prostate cancer patients and may prove helpful in assisting with patient decision making.

Are more options always better? The attraction effect in physicians' decisions about medications.

Consumer choice research has shown that, contrary to normative theory, the introduction of an inferior alternative to an existing choice set can increase the likelihood that one of the original alternatives will be chosen. This phenomenon, the attraction effect, is relevant to physician decision making, particularly when the physician is in the role of a consumer who must make decisions about prescribing medications when a number of alternatives are available. To investigate the attraction effect in physician decision making, 40 internal medicine residents reviewed three patient cases (concerning depression, sinusitis, and vaginitis) and then chose the most appropriate medication for each patient. In some versions of the cases, two medication options were available. Other versions included a third medication (the decoy) that was inferior in every way to one of the original options (the target) but not to the other (the competitor). The results showed that addition of the "decoy" medication increased the likelihood of choosing the target medication. That is, the attraction effect does occur in physicians' decisions about medications. Physicians should be aware of this bias when evaluating or suggesting several similarly attractive medications or treatment options for the same medical condition.

Time preferences and preventive health behavior: acceptance of the influenza vaccine.

BACKGROUND: Many preventive health behaviors involve immediate costs and delayed benefits. Time preference is the extent to which decision makers value future outcomes relative to immediate ones. Consequently, people with future-oriented time preferences should be more likely to adopt preventive measures. The relationship between time preferences and acceptance of a free influenza vaccination was examined. SAMPLE: The participants were 412 corporate employees who were offered free influenza vaccinations at their workplace. MEASURES: Participants' time preferences were measured in each of two domains: money and health. They also reported on whether they had accepted the influenza vaccination and their beliefs and attitudes about the vaccine. RESULTS: There was a small (OR = 2.38) relationship of vaccination acceptance to monetary time preferences but not to the health time-preference measures. Other variables, such as perceived effectiveness of the vaccine, were more predictive. CONCLUSION: This study provides some evidence of a small relationship between time preferences and preventive health behavior.

Framing effects in choices between multioutcome life-expectancy lotteries.

AIM: To explore framing or editing effects and a method to debias framing in a clinical context. METHOD: Clinical scenarios using multioutcome life-expectancy lotteries of equal value required choices between two supplementary drugs that either prolonged or shortened life from the 20-year beneficial effect of a baseline drug. The effects of these supplementary drugs were presented in two conditions, using a between-subjects design. In segregated editing (n = 116) the effects were presented separately from the effects of the baseline drug. In integrated editing (n = 100), effects of supplementary and baseline drugs were combined in the lottery presentation. Each subject responded to 30 problems. To explore one method of debiasing, another 100 subjects made choices after viewing both segregated and integrated editings of 20 problems (dual framing). RESULTS: Statistically significant preference reversals between segregated and integrated editing of pure lotteries occurred only when one framing placed outcomes in the gain domain, and the other framing placed them in the loss domain. When both editings resulted in gain-domain outcomes only, there was no framing effect. There was a related relationship of framing-effect shifts from losses to gains in mixed-lottery-choice problems. Responses to the dual framing condition did not consistently coincide with responses to either single framing. In some situations, dual framing eliminated or lessened framing effects. CONCLUSION: The results support two components of prospect theory, coding outcomes as gains or losses from a reference point, and an s-shaped utility function (concave in gain, convex in loss domains). Presenting both alternative editings of a complex situation prior to choice more fully informs the decision maker and may help to reduce framing effects. Given the extent to which preferences shift in response to alternative presentations, it is unclear which choice represents the subject's "true preferences."

Rationality in medical treatment decisions: is there a sunk-cost effect?

OBJECTIVE: To assess residents' propensity to display the sunk-cost effect, an irrational decision-making bias, in medical treatment decisions; and to compare residents' and undergraduates' susceptibility to the bias in non-medical, everyday behaviors. DESIGN: Cross-sectional, in-person survey. SETTING: Louisiana State University, two locations: Medical Center-Baton Rouge and Main Campus-Psychology Department. PARTICIPANTS: Internal medicine and family practice residents (N = 36, Mdn age = 27) and college undergraduates (N = 40, Mdn age = 20). MEASUREMENTS AND MAIN RESULTS: Residents evaluated medical and non-medical situations that varied the amount of previous investment and whether the present decision maker was the same or different from the person who had made the initial investment. They rated reasons both for continuing the initial decision (e.g., stay with the medication already in use) and for switching to a new alternative (e.g., a different medication). There were two main findings: First, the residents' ratings of whether to continue or switch medical treatments were not influenced by the amount of the initial investment (p's>0.05). Second, residents' reasoning was more normative in medical than in non-medical situations, in which it paralleled that of undergraduates (p's<0.05). CONCLUSIONS: Medical residents' evaluation of treatment decisions reflected good reasoning, in that they were not influenced by the amount of time and/or money that had already been invested in treating a patient. However, the residents did demonstrate a sunk-cost effect in evaluating non-medical situations. Thus, any advantage in decision making that is conferred by medical training appears to be domain specific.

Some cytological features of follicle cells in an ovariole of the carpenter bee (Xylocopa virginica virginica) (L) (Hymenoptera: Apidae).

In an attempt to provide some essential basic data, currently very sparse, on the ultrastructure of solitary bees, the histology, cytology and ultrastructure of thin and ultrathin sections of ovarioles of the adult carpenter beeXylocopa virginica virginica were studied with the light and transmission electron microscopes. The work revealed an apparently previously unreported occurrence of intracellular paired membrane configurations in follicle cells of an ovariole and confirmed the presence in follicle cells of somatic intercellular bridges previously reported in follicle cells in a variety of bees, but not in the carpenter bee. Microtubules and bacteroids were also seen in the follicle cells.