Cysteine residues of SNAP-25 are required for SNARE disassembly and exocytosis, but not for membrane targeting.

The release of neurotransmitter at a synapse occurs via the regulated fusion of synaptic vesicles with the plasma membrane. The fusion of the two lipid bilayers is mediated by a protein complex that includes the plasma membrane target soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment protein (SNAP) receptors (t-SNAREs), syntaxin 1A and synaptosome-associated protein of 25 kDa (SNAP-25), and the vesicle SNARE (v-SNARE), vesicle-associated membrane protein (VAMP). Whereas syntaxin 1A and VAMP are tethered to the membrane by a C-terminal transmembrane domain, SNAP-25 has been suggested to be anchored to the membrane via four palmitoylated cysteine residues. We demonstrate that the cysteine residues of SNAP-25 are not required for membrane localization when syntaxin 1A is present. Analysis of the 7 S and 20 S complexes formed by mutants that lack cysteine residues demonstrates that the cysteines are required for efficient SNARE complex dissociation. Furthermore, these mutants are unable to support exocytosis, as demonstrated by a PC12 cell secretion assay. We hypothesize that syntaxin 1A serves to direct newly synthesized SNAP-25 through the Golgi transport pathway to the axons and synapses, and that palmitoylation of cysteine residues is not required for targeting, but to optimize interactions required for SNARE complex dissociation.

A behavioral analysis of dog bites to children.

Approximately one million dog bites occur yearly in the United States, and 60% to 70% of these are to children. Although the majority of dog bites are not serious, some are disfiguring or, on rare occasions, fatal. Bites are disruptive and stressful but also are preventable. This paper reviews the epidemiology of dog bites, examines the conditions under which bites occur, and discusses behavioral factors related to the dog and to the child that determine whether a bite will occur. Dog bites then are compared with other childhood injuries, and strategies for intervening both before and after a dog bite occurs are discussed.

Teaching young children to use contact lenses.

Young children with surgically removed lenses and extreme nearsightedness can benefit from contact lenses, but their parents may need instruction to teach their children to accept lenses. In this study, 4 children under the age of 5 years were taught contact lens wear using a shaping procedure. Compliance was rewarded with praise and tangibles, and noncompliance was followed with brief time-out for 3 of the children and restraint for the 4th. Three children showed high compliance during an initial shaping procedure, with a decrease in compliance during initial insertion of the lenses. At 3- to 10-month follow-up, levels of compliance were high. Insertion and removal of lenses were accomplished in substantially less time, with little crying and no need for time-out. All 3 children continue to use the lenses daily, and 2 have shown improved visual acuity. The 4th child, who has Down syndrome, showed low levels of compliance with need for physical restraint throughout. Although his parents reported high compliance when he first went home, fitting difficulties and an infection resulted in plummeting of compliance, and contact lens use was discontinued. This procedure has been used successfully at the same hospital with 11 of 13 other children between the ages of 14 months and 7 years 4 months. Implications for selection of suitable candidates for this intervention and ways to decrease costs are discussed.

Do encopretic children have clinically significant behavior problems?

Pediatricians are increasingly recognized as the providers of choice for children with functional encopresis. The presence of clinically significant behavior problems could interfere with pediatric regimens for encopresis, however. To study the extent to which encopretic children exhibit behavior problems, we compared the scores on a standardized behavioral checklist for three randomly selected samples: a sample group of children with encopresis, a sample group of children with behavior problems, and a sample group of children without encopresis or behavior problems. All three samples were matched for age and gender. An analysis of variance showed that the scores of children with encopresis did not differ from the normative sample but were significantly lower than the scores from the behavior problem sample (P less than .00001). The results support the appropriateness of the trend toward expanding the primary pediatrician's role in the treatment of encopresis.

Decreasing dangerous infant behaviors through parent instruction.

One adult and three adolescent mothers with 1-year-old infants were taught to reduce their infants' potential for injury in the home. After being taught to increase their positive interactions with their infants, the mothers were taught to child-proof the home, to use playpen time-out for potentially dangerous behaviors, and to give positive attention for safe behaviors. A multiple baseline design across subjects was used to evaluate functional control. Potentially dangerous behaviors, observed during 10 min of free play, decreased from variable and, at times, high rates during baseline to stable near-zero rates after treatment. These target behaviors remained low at a 7-month follow-up assessment.

Behavioral treatment for common childhood problems.

Parents often consult family physicians about child rearing, child development, and school-related problems. Behavioral treatment is one method of dealing with such concerns. It involves identifying problems with a child's behavior, working to resolve them by rewarding desirable behavior and withholding rewards for undesirable behavior, and evaluating the outcome. Before treatment begins, it is necessary to establish that the parents feel the child's behavior is a problem; that the child can voluntarily control the behavior; that at least one parent or primary caretaker can benefit from instruction in how to modify behavior, and that the behavior to be changed is not just one facet of a larger family problem. Both parents and physicians may find self-help books and printed handouts very useful. Referral to specialized services may be appropriate for complex or recalcitrant problems.

Quantitative computerized analysis of lower incisor changes: a longitudinal implant study in man.

Computer aided interpretation of longitudinal growth data has been presented in summary fashion for four or thirty-six young patients with maxillary and mandibular tantalum implants employing the U.C.S.F. computer program. Broad generalizations of changes in mandibular morphology cannot be made from the small sample. Caution is the watchword in employing so-called natural reference points for superpositioning over an extended period of growth. Identification of cephalometric point B is difficult on a long-term serial basis. The direction of eruption of the lower incisor tip can be followed rather easily and accurately in patients with mandibular implants but varies considerably from patient to patient. Discrepancies arising between customary anatomic tracing methods and implant references have been demonstrated.