The anorectic effect of CNTF does not require action in leptin-responsive neurons.

Leptin resistance is a feature of obesity that poses a significant therapeutic challenge. Any treatment that is effective to reduce body weight in obese patients must overcome or circumvent leptin resistance, which promotes the maintenance of excess body fat in obese individuals. Ciliary neurotrophic factor (CNTF) is unique in its ability to reduce food intake and body weight in obese, leptin-resistant humans and rodents. Although attempts to use CNTF as an obesity therapy failed due to the development of neutralizing antibodies to the drug, efforts to understand mechanisms for CNTF's anorectic effects provide an opportunity to develop new drugs for leptin-resistant individuals. CNTF and leptin share several structural, anatomic, and signaling properties, but it is not understood whether or how the two cytokines might interact to affect energy balance. Here, we conditionally deleted the CNTF receptor (CNTFR) subunit, CNTFRα, in cells expressing leptin receptors. We found that CNTFR signaling in leptin-responsive neurons is not required for endogenous maintenance of energy balance and is not required for the anorectic response to exogenous administration of a CNTF agonist. These results indicate that despite anatomical overlap for CNTF and leptin action, CNTF appears to act within a distinct neuronal population to elicit its potent anorectic effect.

Implications of diet and nutrition for growth and prevalence of anaemia in rural preschool-aged children in Shandong Province, China.

A nutrition surveillance and nutritional improvement programme through nutrition field worker training, nutrition education and encouraging the utilization of home gardens was undertaken among rural preschoolaged children in the four counties of Linshu, Caoxin, Zoucheng and Yucheng in Shandong Province in China from 1990 to 1995. A baseline survey was conducted in 1990. This included physical and biochemical measurements being taken on 3474 children aged 0-5 years and dietary household surveys being taken on a random subsample of 312 children. The baseline survey showed that the average height and weight of the subjects was lower than the World Health Organization (WHO) standard with the prevalence of stunting, underweight and wasting being 24.2, 12.5 and 2.1%, respectively (using the Z scores <= -2 as the cut-off point). The prevalence of anaemia was 61.9% (using haemoglobin (HB) <= 110 g/L as the cut-off point). The range of mean intakes of protein and energy was, respectively, 54.0-67.2% and 56.4-68.4% of the Chinese recommended dietary allowance (RDA) depending on the age group. Mean calcium intake was less than 30% of the RDA for all age groups and the mean intakes of ascorbic acid, niacin, retinol and riboflavin were between 30.6 and 96.1% of the RDA. Nutrition education and nutrition field worker training were the key components of the intervention phase that followed the baseline survey. Over 5 years, 531 nutrition field workers were trained, 1200 parents joined in nutrition classes and approximately 8000 villagers received basic nutrition information. The latter included promotion of breast-feeding, identification of sources of appropriate foods for weaning, and also for the prevention and treatment of common nutritional deficiencies. Home gardens for fruit, vegetable and livestock were also encouraged. The evaluation survey of the project was conducted in 1995 among 2728 0-5- year-old children. The results indicated that the nutritional status of preschool-aged children had improved greatly. The prevalence of stunting and underweight was reduced by 37.8 and 21.3%, respectively, while there was no significant change in the prevalence of wasting. The average rate of anaemia decreased by 79.6% in 1995.

The role of the primary care physician in maximizing cognitive and behavioral recovery from moderate to severe pediatric traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of death and the most common cause of acquired disability in children. Moderate to severe TBI typically results in cognitive deficits, and behavioral and psychosocial adjustment problems, sometimes compromising long term development. Although variable, considerable recovery can occur, especially over the first one to two years post-injury. Appropriate educational and psychological intervention is critical to positive outcome. The primary care physician (PCP) has a major role in monitoring progress and intervention, and therefore in maximizing outcome. The short term neurocognitive and neurobehavioral sequelae and recovery pattern for traumatic brain injury, and the role of the primary care physician in maximizing recovery based on risk factors are described. Some intervention resources are included.

Meaning and development in the interpersonal treatment of severe psychopathology.

As a result of increasing empirical evidence for biological etiologies and economic pressures for rapid symptom relief, treatments for patients with severe psychopathology have become more directive, behavioral, and biomedical. Since a more comprehensive understanding of severe mental disorders is gained through both empirical causal explantation and the discovery of meaning (Carpenter, 1987), clinicians are currently under a greater challenge to help patients cultivate more phenomenologically meaningful change experiences. An interpersonal treatment approach based upon narrative, intersubjective, developmental, and relational principles of understanding severe psychopathology that is complementary to behavioral and biomedical intervention is presented. Four universal maturational processes (interpersonal self, boundary formation, symbolization, response differentiation) are then described and used to illustrate how life-story repair, adjustment, and elaboration can create more meaningful treatment experiences.

Safety, tolerability, and immunogenicity of two regimens of Oka/Merck varicella vaccine (Varivax) in healthy adolescents and adults. Oka/Merck Varicella Vaccine Study Group.

A multicenter clinical trial was conducted among 757 healthy adolescents and adults, 13-54 years, to compare two regimens of Oka/Merck varicella vaccine with respect to safety, tolerability, and immunogenicity. Participants were randomized to receive two injections of vaccine either four or eight weeks apart and were followed for clinical reactions and serologic response. The two vaccine regimens were equally well tolerated. The seroconversion rates (gpELISA) four weeks after injection 1 and 2 were 72 and 99%, respectively, for those who received vaccine four weeks apart and 78 and 99%, respectively, for those who received vaccine eight weeks apart. The differences in seroconversion rates were not statistically significant. However, delaying the second dose to eight weeks resulted in a higher antibody titer one month after the second injection. Administration of a two-dose regimen of varicella vaccine to susceptible adolescents and adults is well tolerated and highly immunogenic.

Verbal learning and memory following pediatric closed-head injury.

In this study, verbal learning and memory following pediatric closed-head injuries (CHI) using the children's version of the California Verbal Learning Test (CVLT). Participants included 47 children, ages 5-16 yr, with a history of CHI, and 47 matched, noninjured controls. Children with CHI performed more poorly than controls on the CVLT, although their deficits varied qualitatively as a function of injury severity. Those with mild/moderate injuries performed as well as controls on learning trials, but they recalled proportionally fewer words after a delay (although their recognition was intact). Severely injured children demonstrated deficits in learning, delayed recall, and recognition, compared to controls. The groups did not differ in learning characteristics, but children with severe CHI exhibited more intrusions than controls. Pediatric CHI are associated with specific disturbances in verbal learning and memory similar to those of adults with CHI but different from those of children with other developmental and neurological disorders.

Reflectivity and learning from aversive events: toward a psychological mechanism for the syndromes of disinhibition.

Gorenstein and Newman (1980) proposed that poorly modulated responding for reward is the common diathesis underlying disinhibited behavior in several traditionally distinct person categories: psychopathy, hysteria, early onset alcoholism, childhood hyperactivity, and nonpathological impulsivity (e.g., extraversion). The authors extend this proposal by theorizing a psychological mechanism that highlights relations among disinhibition, reflection, and failures to learn from aversive feedback. The hypothesized mechanism is presented as 4 generic stages of response modulation: the dominant response set, the reaction to an aversive event, the subsequent behavioral adaptation, and the immediate and long-term consequences of reflection, or the lack thereof. The mechanism has implications for disinhibited individuals' impulsivity and provides a point of departure to study factors responsible for similarities and differences among these syndromes.

Altering a dominant response: performance of psychopaths and low-socialization college students on a cued reaction time task.

The passive avoidance learning deficits of disinhibited Ss have been attributed to their difficulty inhibiting dominant responses. To date, evidence for this hypothesis has been derived from complex tasks. In two experiments, a cued reaction time task requiring no learning or memory was used to evaluate the degree to which groups of disinhibited Ss inhibit simple dominant responses. Disinhibited groups were incarcerated psychopaths identified with Hare's (1985) Psychopathy Checklist and undergraduate males who scored low on the Socialization Scale. Both disinhibited groups committed more errors than controls on trials containing misleading cues, but in both samples, findings were limited to trials in which Ss expected to make right-hand responses. Although alternative interpretations are possible, these data are consistent with the proposal that disinhibited individuals are less likely to inhibit well-established dominant responses.

Delay of gratification in psychopathic and nonpsychopathic offenders.

Delay of gratification is a prototypical measure of self-control that merits systematic investigation in psychopaths. White male prisoners were provided with repeated opportunities to select an immediate response with uncertain reward or a delayed response with a higher rate of reward under one of three incentive conditions. Psychopaths' performance depended on their level of trait anxiety and incentive condition: Whereas low-anxious psychopaths were relatively unwilling to delay when omission of expected rewards also incurred monetary punishments, they displayed relatively superior performance when the task involved rewards only. Findings complement those for passive avoidance learning in psychopaths and suggest that inhibitory self-control in low-anxious psychopaths is somewhat impaired under conditions involving a combination of monetary rewards and punishments.

Modified cases of chickenpox after varicella vaccination: correlation of protection with antibody response.

Four thousand forty-two healthy children and adolescents, ages 12 months to 17 years, were vaccinated with a single dose of live attenuated varicella vaccine (VARIVAX; Merck Sharp and Dohme Research Laboratories) containing approximately 1000 to 1625 plaque-forming units/dose during clinical trials conducted from 1987 to 1989. Clinical follow-up of vaccinees revealed that 2.1 and 2.4% of vaccinees developed modified cases of varicella in the first and second years, respectively, after vaccination. Most of those who developed varicella postvaccination had an attenuated illness, characterized by fewer lesions and a lower incidence of fever (greater than or equal to 100 degrees F, oral) than after natural infection. The likelihood of developing varicella postvaccination decreased (P less than 0.0001) as the 6-week postvaccination glycoprotein-based enzyme-linked immunosorbent assay titer increased. In addition the number of lesions in these cases tended to decrease (P = 0.07 for Year 1 and P = 0.02 for Year 2) as the 6-week glycoprotein-based enzyme-linked immunosorbent assay titer increased. Thus the 6-week postvaccination glycoprotein-based enzyme-linked immunosorbent assay titer can be used as a surrogate marker for protection from natural disease.

Trace element nutrition status and dietary intake of children with phenylketonuria.

The trace element status (copper, iron, zinc, manganese, chromium, and selenium) of 20 dietetically treated phenylketonuric (PKU) children was assessed. Significantly higher intakes of copper (p = 0.002) and iron (p = 0.005) were noted in PKU children compared with their siblings. No significant differences were found for zinc, manganese, or chromium. Intake of selenium was significantly lower (p = 0.0001) in PKU children (8.4 +/- 3.9 micrograms/d) than in siblings (41.6 +/- 9.4 micrograms/d). Plasma and urine selenium and erythrocyte glutathione peroxidase activity (GSHpx) were significantly lower (p = 0.001) in PKU children (0.38 +/- 0.11 mumol/L, 58.0 +/- 34.5 nmol/d, and 14.2 +/- 5.5 U/g Hb, respectively) than in siblings (0.82 +/- 0.15 mumol/L, 165.2 +/- 49.4 nmol/d, and 22.7 +/- 5.2 U/g Hb, respectively). No differences were found in plasma and urine concentrations of other elements. Intake of selenium was significantly correlated with erythrocyte GSHpx (r = 0.87, p = 0.0001) and plasma selenium (r = 0.71, p = 0.0001) for the combined groups. The need and possible procedures, including dietary manipulation, for increasing selenium intake in PKU subjects are discussed.

Preinjury psychopathology in trauma patients.

One hundred patients admitted to a Level I trauma center were interviewed using the Langner 22-item index of psychiatric symptoms to evaluate pre-existing psychological pathology. The medical chart was also examined for any type of note or evidence of psychiatric consultation efforts by the surgical attending staff. There were 74 males and 26 females in the sample, with a mean age of 33 years. Types of injuries included blunt trauma in 71% and penetrating trauma in 29% of the group, respectively. Eight per cent of these injuries were self inflicted. The mean Injury Severity Score was 17. Alcoholic intoxication was documented in 49%. We found that severe psychopathology as defined by the Langner Index was present in 88% of those admitted with penetrating trauma, in 47% of those admitted with blunt trauma, and in 75% of the intoxicated group. In only 14% of the sample was psychopathology documented in the chart by the attending staff. Preinjury psychopathology in trauma patients was commonly present and seemed to be most highly associated with penetrating trauma and alcohol use.

Reaction to punishment, reflectivity, and passive avoidance learning in extraverts.

Passive avoidance learning occupies a central role in accounts of disinhibited behavior, ranging from psychopaths' persistent criminality (Hare 1970) to extraverts' gregariousness (Gray, 1972). To explore the mechanism underlying passive avoidance deficits, we assessed the relation of extraversion, neuroticism, and response latency after punishment to passive avoidance learning by using two successive go/no go discrimination tasks. The tasks were designed to examine two aspects of subjects' reactions to punishment: response speed on trials immediately following punishment (Experiment 1) and time to terminate punishment feedback between successive trials (i.e., reflectivity; Experiment 2). Consistent with previous findings, the results of Experiment 1 showed that extraverts commit more passive avoidance errors than introverts do (Newman, Widom, & Nathan, 1985) and fail to pause following punished errors (Nichols & Newman, 1986). In Experiment 2, only neurotic extraverts displayed this pattern of performance differences. In both experiments, longer pausing following punishment predicted better learning from punishment for both introverts and extraverts. These results suggest that, in the presence of salient cues for reward, extraverts' characteristic reaction to punishment interferes with processing punished errors and may contribute to their more general propensity for impulsive, nonreflective action.

A monoclonal antibody directed to N-acetylneuraminosyl-alpha 2 leads to 6-galactosyl residue in gangliosides and glycoproteins.

A hybridoma cell line producing a monoclonal antibody directed to N-acetylneuraminosyl-alpha 2 leads to 6-galactosyl residue has been established. The antibody is IgG2b and reacts only with lacto-series gangliosides as well as with glycoproteins having an N-acetylneuraminosyl-alpha 2 leads to 6-galactosyl residue, but does not react with gangliosides or glycoproteins having an N-acetylneuraminosyl-alpha 2 leads to 3- or -alpha 2 leads to 4-galactosyl residue. The antibody is useful for detecting the specific carbohydrate chain having this terminal structure by immunostaining of glycolipids separated on thin layer chromatography or glycoproteins separated on gel electrophoresis after blotting on nitrocellulose sheet. A remarkable accumulation of a few gangliosides having this terminal structure has been detected by this monoclonal antibody in some human cancer.

Human cancer-associated gangliosides defined by a monoclonal antibody (IB9) directed to sialosyl alpha 2 leads to 6 galactosyl residue: a preliminary note.

A new monoclonal antibody (IB9) was prepared by hybridoma technique directed specifically to sialosyl alpha 2 leads to 6 galactosyl residue. With this reagent, accumulation of two major gangliosides in human colonic and liver adenocarcinoma has been detected, and these gangliosides were isolated and characterized as structures A and B (below). Another ganglioside with a ceramide nonasaccharide structure, which reacted to anti-X-hapten antibody after desialylation, was also isolated and partially characterized. (formula; see text) These gangliosides were absent or present in very small quantity in normal tissue and may represent human cancer-associated markers.

Lipid and protein histochemistry of enamel--effects of fluoride.

Staining reactions for a number of histochemical procedures for lipophilic staining and protein were studied in the enamel matrix along the length of rat incisors. Sudan Black gave a positive stain across the whole thickness of very early enamel (up to 30 micrometer) but this staining only continued as a narrow band close to the ameloblasts as the enamel matured. A variety of tests for protein produced almost identical staining patterns in enamel matrix up to 100 micrometer thick. Since the pattern of "lipid" staining persisted, after using a number of procedures which could normally be expected to remove lipid, it is suggested that Sudan Black positive staining may be due to lipophilic protein rather than lipid itself. Fluoride did not significantly alter the staining reactions for "lipid" and protein but did produce matrix which was much more effectively stained by cross-linking agents FFDNB and FF sulphone.