Search

Studies in humans and animal models (including rodents) have revealed lasting behavioral and cognitive impairments in offspring prenatally exposed to nicotine. Offspring of pregnant mouse dams prenatally subjected to 9-10 daily subcutaneous injections into the nape of the neck during pregnancy have been postnatally subjected to several developmental and behavioral tests to investigate the effects of prenatal nicotine exposure on those offspring at various stages of their life. The prenatal exposure to nicotine has resulted in significant reduced postnatal body weight gain, as well as in significant delay in eye opening, in the appearance of body hairs, and in sensory motor reflexes. However, motor activity was significantly stimulated in early adulthood of mouse pups prenatally exposed to nicotine, and such exposure proved to have long-lasting hyperactive effects on mice. Thus, exposure to nicotine during a critical prenatal period of brain development deduced from the present study in mice raises the alarm of the possible hazard of prenatal exposure to nicotine in humans. Hence, smoking by pregnant women might constitute a serious hazard to their in utero developing children.

Play behavior was assessed in two inbred strains of rats. Rats of the Fischer-344 strain (F344) were found to be less playful than Buffalo rats after social isolation, as evident from fewer pins and fewer playful attacks to the nape. When tested in same-strain pairings, overall defense of the nape did not differ between strains, although there were strain differences in the specific pattern of defense. When tested in cross-strain pairings, F344 rats were less likely to direct nape attacks toward a Buffalo play partner, and were also less likely to defend their nape when attacked by Buffalo rats. Although different levels of pinning and nape attacks in the two strains were dependent on the amount of isolation prior to the play period, differences in nape defense were not dependent on prior isolation. This pattern of results suggests that the neural mechanisms for playful attack differ from those underlying playful defense. These data also suggest that the F344 strain could be useful in better understanding the neural and genetic bases of mammalian playfulness.

N-Acylphosphatidylethanolamine (NAPE) is an unusual derivative of the common membrane phospholipid, phosphatidylethanolamine (PE), with a third fatty acyl group attached through an amide linkage to the amino group of ethanolamine. NAPE has been reported to occur in various amounts in lipid extracts from a variety of seeds (Schmid et al., 1990). In reports where isolated NAPE was subjected to rigorous chemical analyses (analyses of degradative products and IR spectroscopy), it was estimated to account for approximately 4 mol% of lipid P in wheat (Bomstein 1969), 5% in pea, 3.5% in soybean, and 13.3% in oat (Dawson et al., 1969). Recent data with different tissues and organs of cotton seedlings and cotyledons at several different developmental stages indicated the NAPE was present in all parts of cotton plants at concentrations between 1.9 and 3.2 mol% of the total phospholipids (Chapman and Sprinkle, 1996). Cottonseed NAPE was characterized structurally by FAB-MS/MS analyses (Chapman and Moore, 1993a; Sandoval et al., 1995), and the major molecular species were identified as 16:0/18:2 PE (N-palmitoyl), 16:0/18:2 PE (N-linoleoyl), and 18:2/18:2 PE (N-palmitoyl).

A 51-year-old woman presented with a 1-year historyof an asymptomatic figurate skin lesion that hadgradually developed on the nape of her neck. Thepatient’s personal medical history was unremarkable.Examination revealed a 6-cm diameter, pink–red,geometrically delimited, embossed C-shaped plaqueresembling a cattle brand (Fig. 1). An irregular hypo-pigmented macular area measuring 2 cm across arosefrom the tips of the C-shaped outline and extendedoutwards. A punch biopsy of the rim of the lesion wasperformed.

Understanding the mechanisms involved in the biogenesis ofN-arachidonoylethanolamine (anandamide) andNpalmitoylethanolamine is important in view of the possible role of these lipids as endogenous cannabinoid substances. Anandamide (which activates cannabinoid CB1 receptors) andN-palmitoylethanolamine (which activates a CB2-like receptor subtype in mast cells) may both derive from cleavage of precursor phospholipid,N-acylphosphatidylethanolamine (NAPE), catalyzed by Ca2+-activated D-type phosphodiesterase activity. We report here that thede novobiosynthesis of NAPE is enhanced in a Ca2+-dependent manner when rat cortical neurons are stimulated with the Ca2+-ionophore ionomycin or with membrane-depolarizing agents such as veratridine and kainate. This reaction is likely to be mediated by a neuronalN-acyltransferase activity, which catalyzes the transfer of an acyl group from phosphatidylcholine to the ethanolamine moiety of phosphatidylethanolamine. In addition, we show that Ca2+-dependent NAPE biosynthesis is potentiated by agents that increase cAMP levels, including forskolin and vasoactive intestinal peptide. Our results thus indicate that NAPE levels in cortical neurons are controlled by Ca2+ions and cAMP. Such regulatory effect may participate in maintaining a supply of cannabimimeticN-acylethanolamines during synaptic activity, and prime target neurons for release of these bioactive lipids.

Enucleated juvenile rats were compared to sighted juveniles, and tested over six trials. In some of these trials, the vibrissae were clipped and the test chamber was flooded with white noise. Even though the enucleated rats played, they did so in an atypical manner. They tended to initiate more playful and other social contacts, and were more likely to defend themselves if contacted. When they did defend themselves, they adopted behavior patterns that were more likely to evade the partner's attack. In addition, the enucleated rats were hypersensitive to the partner, being more likely to respond defensively when contacted further from the nape (the main play target). All these changes in play fighting by nonsighted rats suggest that the loss of vision leads to motivational changes in activity and reactivity, and so has an indirect effect on play behavior. In addition, direct evidence is also provided to show that vision is used to orient attacks to the nape. When the vibrissae were closely clipped, the sighted rats continued to make direct attacks on the partner's napes, whereas the nonsighted rats did not. Rather, they first contacted some other part of the partner's body and then oriented to the nape. Another test paradigm was used to determine whether vision is used to trigger defensive responses. The rats were partially food deprived as adults and were filmed in a food wrenching and dodging situation where one rat was given a food pellet and the other allowed to steal it. Measurement of the distance at initiation of the lateral swerve away from the approaching partner (i.e., dodge) showed that when the vibrissae are clipped, the sighted rats continued to initiate dodges at the same distance, whereas the nonsighted rats could not. Therefore, vision appears to have an active role in organizing movement sequences of attack and defense in play fighting and other close-quarter interactions.

We studied the localization of N-acyl phosphatidylethanolamine (NAPE), a putative cannabinoid precursor, in primary cultures of striatal and cortical neurons from the rat brain. We probed intact neurons with various exogenous phospholipases, including S. chromofuscus phospholipase D (PLD). S. chromofuscus PLD does not penetrate into neurons (as demonstrated by a lack of internalization of 125I-labeled PLD), and does not cause gross damage to the neuronal membrane (as demonstrated by a lack of effect of PLD on [3H]gamma-aminobutyric acid release). When neurons, labeled to isotopic equilibrium with [3H]ethanolamine, were incubated for 10 min with S. chromofuscus PLD, approximately 50% of neuronal NAPE was hydrolysed. This hydrolysis was accompanied by the release of a family of N-acyl ethanolamines (NAE) (assessed by high performance liquid chromatography), which included the cannabinoid receptor agonist, anandamide. Exogenous phospholipase A2 (PLA2) (Apis mellifera) and PLC (B. cereus) mobilized [3H]arachidonate and [3H]diacylglycerol, respectively, but had no effect on NAE formation under these conditions. These experiments indicate that approximately 50% of neuronal NAPE is localized in a compartment that is easily accessible to extracellular PLD, possibly the plasmalemma, where it would also be easily hydrolyzed upon stimulation to produce NAE.

N-Acylphosphatidylethanolamine (NAPE), an unusual acylated derivative of phosphatidylethanolamine (PE), was recently shown to be synthesized from PE and free fatty acids in cotyledons of cotton (Gossypium hirsutum L.) seedlings (K.D. Chapman, T.S. Moore [1993] Plant Physiol 102: 761–769). Here we report that NAPE is present in dry seeds of cotton and increases with time of imbibition from 2.31 nmol/seed in dry seeds to 4.26 nmol/seed in 4-h-soaked seeds. Total phospholipid/seed also increased such that the relative percentage of NAPE was similar in dry and soaked seeds (2.3 mol% compared to 2.6 mol%, respectively). The major molecular species of NAPE were identified in both dry and soaked seeds by fast atom bombardment mass spectrometry and collisionally activated dissociation tandem mass spectrometry as 16:0/18:2-PE(N-palmitoyl), 16:0/18:2-PE(N-linoleoyl), and 18:2/18:2-PE(N-palmitoyl). The specific activity of NAPE synthase in seed extracts increased with increasing time of imbibition from 35 pmol h-1 mg-1 protein in dry seeds to 129 pmol h-1 mg-1 protein in 4-h-soaked seeds. Collectively, our results indicate that NAPE is present in dry cottonseeds and synthesized during imbibition. The biosynthesis of NAPE provides a mechanism for maintaining membrane integrity during seed rehydration and may indicate that NAPE plays a protective role in intracellular membranes of plant tissues, as has been suggested for intracellular membranes of animal tissues.

N -acylphosphatidylethanolamine (NAPE) was recently shown to be synthesized in vitro in cottonseed microsomes by the direct N-acylation of phosphatidylethanolamine (PE) with unesterified fatty acids (K. D. Chapman and T. S. Moore, 1993, Plant Physiol . 102, 761-769), Here we examine the relationship of the synthesis and turnover of NAPE in cottonseed microsomes to the O-acylation of other membrane phospholipids. PE was N-acylated in a time-dependent manner with [1- 14 C]palmitic acid independent of exogenously supplied ATP, O-Acylation of PE and phosphatidylcholine (PC) with [1- 14 C]palmitic acid proceeded only in the presence of ATP. Further radiolabeling experiments with [1- 14 C]palmitoylCoA and phosphatidyl( N -[1- 14 C]palmitoyl)ethanolamine indicated that O-acylation of phospholipids occurred via an acylCoA intermediate and not via an NAPE intermediate, [1- 14 C]palmitic acid was released from PC[1- 14 C-dipalmitoyl] in cottonseed microsomes in a Ca 2+ -dependent manner and this [ 14 C]-FFA was incorporated into [ 14 C]NAPE in a linear fashion. Cottonseed NAPE was selectively hydrolyzed to N -acylethanolamine (NAE) and N -acyl lysophosphatidylethanolamine (NAlysoPE) by Ca 2+ -independent, membrane-bound phospholipase D and A activities, respectively. NAlysoPE was not hydrolyzed to NAE, indicating that the phospholipase D that was active to ward NAPE did not recognize NAlysoPE; instead NAlysoPE was converted to NAPE in the presence of Ca 2+ . Collectively, our results indicate that NAPE synthesis and the O-acylation of other phospholipids occur by two separate pathways and that microsomal NAPE is selectively turned over by membrane-bound phospholipase activities. A pathway for the metabolism of cottonseed NAPE is outlined.

Play fighting by juvenile rats involves playful attacks directed at the partner's nape, where successful contact leads to gentle rubbing of the snout into the nape area. In addition, the recipient of such contact may defend the nape by adoping tactics of playful defense. The two most common defensive tactics in the juvenile period are evasion, where the recipient swerves or leaps away and facing defense involving rotation to supine, where the attacker is faced and its further attempts to contact the nape are blocked. An unresolved issue is whether the nape contact itself or defense by the recipient alone or in combination with nape contact, are involved in rewarding play fighting. In this study, drug-induced non-playful partners were used to test the ‘motivation’ for play fighting when only playful nape contact was possible. In drug-trials compared to baseline and saline trials, both neonatally androgenized females (high players) and control, oil-treated, females (low players), decreased the frequency of launching nape attacks. These results suggest that nape contact alone, in the absence of defense by the recipient, is not sufficient reinforcement for such playful activity, irrespective of the initial playfulness of the subjects. However, while nape attacks decrease, other forms of social contact, such as anogenital investigation and climbing over the partner (i.e., crawl overs), increase in frequency. These results suggest that non-playful partners are not neutral targets for normal rats. Rather, the ‘non-normal’ behavior of the drugged target may affect the subjects' behavior in such a way as to reduce their playfulness for reasons other than reduced reinforcement for play.

N--Acyl-phosphatidylethanolamine (NAPE)was first described from plants by Bomstein [1]. Further work on its occurrence and biosynthesis were discontinued when a similarly behaving compound was found to be an artifact of the extraction procedures and identified as N-methyl-phosphatidylethanolamine [2]. In 1991, however, Chapman and Trelease [3] noted a spot on thin-layer chromatograms of radiolabeled phospholipids from cotton cotyledons which was tentatively identified as NAPE In light of these results, we chose to examine the occurrence, structure and origin of the putative NAPE in more detail.

Treatment with d-amphetamine has been shown to cause a decrease in play fighting by juvenile rats. Previous studies, however, did not determine if all behavioral components of play were equally diminished. In this study, the effects of amphetamine on both the attack and defense patterns of play fighting were analyzed. Experiment 1 shows that a 0.5 mg/kg dose, injected subcutaneously in the nape, decreases both attack and defense. In contrast, Experiment 2 shows that the same dose, injected subcutaneously in the hip, decreases the level of attack to a similar level, but does not significantly affect defense. This suggests that while the 0.5 mg/kg dose of amphetamine is primarily affecting the attack components of play, via its action on the central nervous systems, the reduced likelihood of defense for those rats injected in the nape probably results from a local anesthetic effect, which numbs the area of the body defended during play fighting. Further doses (0.15 & 1.0 mg/kg), injected in the hip, were also tested. The highest dose decreased both components of play. The lowest dose had no effect on either attack or defense. It is suggested that the attack and defensive components of play fighting may be mediated by different neural systems.

In rats (Rattus norvegicus), juvenile males engage in more play fighting (a male-typical behavior) than do juvenile females, and this difference is based on perinatal influences of androgens. We show that there are qualitative and quantitative differences between the sexes in the type of defensive responses and their manner of execution. In defensive responses rats try to avoid having their napes contacted by the partner's snout. The sex differences arise from females' greater response distance; that is, females responded to an approach when the partner's snout was further from the nape. This permits females to use different defensive responses and to use them more successfully. This greater response distance is defeminized by the neonatal administration of testosterone propionate. Our findings suggest that play fighting in rats has both male- and female-typical features and that these are, at least in part, influenced perinatally by androgens.

We recently reported that a novel acyltransferase activity (fatty acid : diacylphosphatidylethanolamine N-acyltransferase) synthesizes N-acylphosphatidylethanolamine (NAPE), an unusual derivative of phosphatidylethanolamine (PE), in microsomes of cotyledons of cotton seedlings by direct acylation of PE with free fatty acids (Chapman and Moore (1993) Plant Physiol. 102(3), 761–769). Here we report the solubilization of this membrane-bound NAPE synthase activity from cottonseed microsomes and the separation of three active isozymes with distinctly different characteristics. NAPE synthase activity was solubilized from NaCl-washed microsomal membranes by 0.2 mM dodecylmaltoside (DDM) at a 2:1 (w:w) detergent/protein ratio (assessed by enzyme activity after centrifugation at 150000 × gmax, 1 h). Two sequential preparative isoelectric focussing separations of DDM-solubilized microsomal membrane proteins resulted in recovery of three distinct peaks of NAPE synthase activity - one at pH 6.3, one at pH 7.2, and one at pH 8.4 (designated A, B and C). These isozymes were purified 1148-fold (A), 269-fold (B), and 729-fold (C) from homogenates of cotton cotyledons. A 28 kDa subunit was enriched in all three isozyme fractions. Each of the isozymes exhibited unique kinetic properties with respect to palmitic acid and dioleoyl-PE. Each of the solubilized isozymes exhibited positive cooperativity toward palmitic acid (consistent with previous studies of NAPE synthase activity in intact microsomes) but not toward dioleyl-PE. Collectively, these results indicate that the synthesis of NAPE in cotton cotyledons is complex and has a potential for being a highly regulated process. The isolation of active NAPE synthase isozymes will provide the foundation for future studies into the physiological role of NAPE synthase (and NAPE) and the regulation of NAPE metabolism in membranes of plant cells.

We report a Japanese girl with atypical lipodystrophia centrifugalis abdominalis infantilis. The initial lesion developed on the neck as an area of erythema which showed centrifugal spread to the nape, submandibular area and upper breast and central fading to leave a residual depression and purplish brown pigmentation symmetrically. A central depression on the neck, nape, submandibular area and upper breast was surrounded by a distinctive erythematous, slightly elevated and indurated border. Histological examination of the erythematous border revealed inflammatory changes in the subcutaneous fat. Although this patient was affected in an unusual site, we concluded that she had lipodystrophia centrifugalis abdominalis infantilis, because of the overall features of the lesions.

Background: N-acylethanolamines (NAEs) are long chain fatty acid ethanolamides which are present in almost all mammalian tissues including the gastrointestinal (GI) tract. NAEs are synthesized from the hydrolysis of phospholipid precursors N-acylphosphatidylethanolamines (NAPEs) by N-acylphosphatidylethanolamine-hydrolyzing phospholipase D (NAPEPLD). Despite their abundance, the physiologic roles of C16:0 and C18:1 NAPEs in the GI tract are not known. They may induce their effects directly or by conversion to Npalmitoylethanolamine (C16:0) or N-oleoylethanolamine (C18:1). We examined whether i) C16:0 or C18:1 NAPE regulates GI motility in the mouse, and ii) if these effects are through the endocannabinoid system involving NAPE-PLD and the cannabinoid 1 (CB1) receptor. Methods: Wild type, NAPE-PLD -/or CB1-/mice were used. The effects of C16:0 and C18:1 NAPEs on contractility of the intestine to electrical field stimulation (EFS; 4Hz, 60 Volts) and bethanechol (10μM) were studied in an organ bath In Vitro. Whole gut transit of an Evans blue marker after treatment with NAPEs (1-10 mg/kg i.p.) was studied In Vivo. NAPE-PLD mRNA expression after treatment with NAPEs was measured by real-time PCR. Results: C16:0 NAPE (up to 10 μM) reduced EFS induced contractions by ~ 41% in the ileum and ~ 44% in the colon of wild type mice. C18:1 NAPE had no effect in either region of the intestine. AM251 (100nM), a CB1 antagonist, blocked the effect of C16:0 NAPE on EFS contractility in the ileum but not the colon. Organ bath experiments on CB1-/mice confirmed these findings, as C16:0 NAPE did not have any effect in the ileum of those mice; however, it was still active in the colon. In NAPE-PLD -/mice, the effect of C16:0 NAPE was completely abolished in the ileum but not the colon (~42% inhibition at 10 μM). C16:0 or C18:1 NAPE had no effect on contractions induced by bethanechol. C16:0 NAPE dose-dependently increased whole gut transit time with ~100% increase at 10 mg/kg compared to the vehicle treated mice. AM251 blocked this effect. C18:1 NAPE had no effect on whole gut transit up to 10mg/kg. C16:0 or C18:1 NAPE (50 mg/kg i.p.) did not change NAPE-PLD mRNA expression in either ileum or colon of wild type mice. Conclusion: C16:0 but not C18:1 NAPE modulates GI motility. This effect requires the conversion of the NAPEs to a CB1 receptor ligand by NAPE-PLD in the ileum, but it involves other pathways in the colon. This study suggests some NAPEs may have a role as physiologic regulators of GI motility.

As reported earlier (Gulaya, N.M., Vaskovsky, V.E., Vysotsky, M.V., Volkov, G.L., Govseeva, N.N. and Artemenko, I.P. (1988) Ukr. Biochim. J. 60, 58–63), N -acylphosphatidylethanolamines (NAPE) and products of their catabolism, N -acylethanolamines (NAE), are present in the lipids of neuroblastoma C1300 N18 undifferentiated cells. The present paper describes the distribution of NAE added to culture medium of differentiated cells and its effect on the fast sodium channels and some other membrane characteristics. It is shown that NAE inhibits the destroying action of veratridine on membranes.

To the Editor.— We report a case of congenital tail-like protrusion on the nape of the neck associated with underlying cervical spina bifida. Report of a Case.— A 6-year-old boy was seen for removal of a protrusion on the nape of his neck. He had been delivered normally at term. The protrusion had been noted at birth and had shown no movement after any stimulation. He had shown neither neurologic abnormalities nor difficulty in motion of the upper extremities during the intervening 6 years. Physical examination revealed that the patient was well developed and had normal mental functions. The tapering protrusion was 1 cm long, with a diameter of 0.5 cm at its constricted basal portion located on the midline at the level of cervical vertebrae C-2 to C-3 (Fig 1). It was soft and had terminal hairs, and its mobility along with the underlying tissue was poor. Neurologic findings

When grasped by the skin of the nape and lifted into the air, the young of many altricial mammals exhibit an immobility response in which they tuck their limbs against their bodies and remain inert. Such a response can be induced in the adults of some species, especially if a stronger tactile stimulus such as bandaging the head and neck or clamping the skin of the nape, is applied. In this study, the immobility response of the Mongolian gerbil ( Meriones unguiculatus ) is investigated, which appears to differ in potentially useful ways from other commonly studied species such as rats ( Rattus norvegicus ). It has been previously reported that for rats clamping or bandaging had a more profound effect on the immobility response than grasping. Mongolian gerbils were tested will all three methods (grasping, bandaging and clamping), which were repeated at intertrial intervals ranging from 3 h to 40 days. Grasping induced a significantly longer duration of immobility than either bandaging or clamping. However, repeated trials significantly increased the duration of immobility induced by clamping, whereas repeated grasping or bandaging did not do so. The marked difference in the induction of the immobility response in gerbils as compared to rats, may provide a useful model for the study of this behavior.

We have identified a microsomal phospholipid as Nacylphosphatidylethanolamine (NAPE) that was radio-labeled following incubation of 1-day-old cotyledons of cotton seedlings with [ 14 C]ethanolamine. Radiolabeled NAPE comigrated with commercially available L-α-dipalmitoyl phosphatidyl( N -palmitoyl)ethanolamine (stdNAPE) in one- and two-dimensional TLC. This NAPE comprised 7.2 ± 1.0% (by weight) of microsomal phospholipids when hot isopropanol was used to inactivate endogenous phospholipases prior to extraction of lipids. In vitro degradation of putative cottonseed radiolabeled NAPE by Streptomyces chromofuscus phospholipase D resulted in production of a ninhydrin-reactive, radiolabeled lipid which comigrated with N -acylethanolamine (NAE) that was produced from a similar enzymatic cleavage of std-NAPE. Transmethylation of cottonseed radiolabeled NAE yielded radiolabeled ethanolamine and fatty acid methyl esters, nearly all of which were saturated (myristate, palmitate, and stearate together were 92% of the acyl components of cottonseed NAE). Positional analysis and relative abundance of the O -acyl groups of cottonseed microsomal NAPE were determined following a double enzymatic cleavage with Trimeresurus flavoviridis venom (phospholipase A 2 activity) and S. chromofuscus phospholipase D. We substantiated our identification of cottonseed NAPE by 1 H NMR spectroscopy and by mass spectrometry (fast-atom-bombardment ionization and tandem MS, FAB-MS/MS). Radiolabeled NAPE was synthesized in vivo in varying amounts from [ 14 C]ethanolamine applied to maturing seeds of cotton and soybean, cotyledons of dark-grown cotton and soybean seedlings, cotyledons of light-grown okra, cotton and soybean seedlings, endosperm tissue of castor bean, and suspension cell cultures of rice. In pulse-chase radiolaheling experiments in cotyledons of 1-day-old cotton seedlings, radiolabeled NAPE increased and radiolabeled phosphatidylethanolamine (PE) decreased over a 12-h chase period (in the dark or light), suggesting that NAPE was synthesized from PE in vivo . In vitro , the synthesis of NAPE from PE (radiolabeled in vivo ) proceeded in a linear fashion in microsomes of cotton cotyledons with or without 1 mM EGTA and with or without 1 mM CaCl 2 for 90 min. NAPE was synthesized in vitro from PE synthesized by the exchange pathway (microsomes preincubated with [ 14 C]ethanolamine) and from PE synthesized by the nucleotide pathway (microsomes preincubated with [ 14 C]CDPethanolamine). Collectively, our data indicate that (a) NAPE is a widespread, natural phospholipid component of plants, (b) NAPE is synthesized in vivo under normal physiological growth conditions in cotyledons of cotton seedlings, (c) NAPE is localized and synthesized in cottonseed microsomes, and (d) NAPE is likely synthesized by a direct acylation of PE.

We report a rare case of spinal metastasis from eccrine carcinoma of the nape of the neck four years after resection of the primary lesion. There was local recurrence at the same site apart from the spinal metastasis. The spinal lesion involved the pedicle and body of the D-9 vertebra with an extradural component compressing the cord. MR appearance was that of any metastatic deposit, hypointense on T1 and hyperintense on T2.

Acne inversa (AI), also known as hidradenitis suppurativa, is a chronic, recurrent, inflammatory disease of hair follicles that often runs in families. We studied six Chinese families with features of AI as well as additional skin lesions on back, face, nape, and waist and found independent loss-of-function mutations in PSENEN, PSEN1, or NCSTN, the genes encoding essential components of the γ-secretase multiprotein complex. Our results identify the γ-secretase component genes as the culprits for a subset of familial AI, implicate the γ-secretase-Notch pathway in the molecular pathogenesis of AI, and demonstrate that familial AI can be an allelic disorder of early-onset familial Alzheimer's disease.

The biosynthesis of the endocannabinoid anandamide (AEA) and related N-acyl ethanolamine (NAE) lipids is complex and appears to involve multiple pathways, including: (1) direct release of NAEs from N-acyl phosphatidyl ethanolamine (NAPE) precursors by the phosphodiesterase NAPE-PLD, and (2) double O-deacylation of NAPEs followed by phosphodiester bond hydrolysis of the resulting glycero-phospho (GP)-NAEs. We recently identified GDE1 as a GP-NAE phosphodiesterase that may be involved in the second pathway. Here, we report the generation and characterization of GDE1(-/-) mice, which are viable and overtly normal in their cage behavior. Brain homogenates from GDE1(-/-) mice exhibit a near-complete loss of detectable GP-NAE phosphodiesterase activity; however, bulk brain levels of AEA and other NAEs were unaltered in these animals. To address the possibility of compensatory pathways, we generated GDE1(-/-)/NAPE-PLD(-/-) mice. Conversion of NAPE to NAE was virtually undetectable in brain homogenates from these animals as measured under standard assay conditions, but again, bulk changes in brain NAEs were not observed. Interestingly, significant reductions in the accumulation of brain NAEs, including anandamide, were detected in GDE1(-/-)/NAPE-PLD(-/-) mice treated with a fatty acid amide hydrolase (FAAH) inhibitor that blocks NAE degradation. Finally, we determined that primary neurons from GDE1(-/-)/NAPE-PLD(-/-) mice can convert NAPEs to NAEs by a pathway that is not preserved following cell homogenization. In summary, combined inactivation of GDE1 and NAPE-PLD results in partial disruption of NAE biosynthesis, while also pointing to the existence of an additional enzymatic pathway(s) that converts NAPEs to NAEs. Characterization of this pathway should provide clarity on the multifaceted nature of NAE biosynthesis.

1. Mitochondria were isolated from the furcular, subcutaneous, abdominal, nape and lateral adipose tissue depots of five species of bird (pheasant, Japanese quail, pigeon, house sparrow and great tit) acclimatized to the Northern winter. 2. Mitochondrial proteins were separated by SDS-polyacrylamide gel electrophoresis, blotted onto nitrocellulose membranes, and probed for the presence of the 32,000-33,000 Mr uncoupling protein characteristic of "mammalian" brown adipose tissue, using an anti-(ground squirrel uncoupling protein)serum. 3. Immunoreactivity consistent with uncoupling protein was not detected in mitochondria from any of the avian adipose tissues. Immunoreactivity was, however, evident in mitochondria from perirenal or interscapular adipose tissue from a range of mammals--rats, mice, golden hamsters, Orkney voles, wood mice, pipistrelle bats, wood lemmings, and newborn lambs, cattle, reindeer and red deer. 4. These results provide biochemical evidence that "mammalian-like" thermogenic brown adipose tissue is absent from avian species; adipose tissues in birds appear to be functionally "white".

The dorsal immobility response (DIR) is typically seen in the infants of many altricial mammalian species. Lifting the animal into the air by the nape of the neck is the primary releasing stimulus. Functionally, this response appears to facilitate carrying of the infants by the adults. When grasped by the nape and lifted into the air, adult rats will also exhibit the DIR. In this paper, the role of the labyrinths in the DIR of adult male rats was examined. Vestibular stimulation produced by vertical circular acceleration increased the duration of the DIR, while labyrinthectomy greatly diminished the DIR. In rats with intact labyrinths, visual occlusion greatly potentiated the DIR, whereas, in labyrinthectomized rats, visual occlusion had little effect. These data indicate that the vestibular system plays a major role in mediating the DIR of adult rats. The retention of the DIR into adulthood and the possible increased role of the labyrinths in the control of the adult DIR, are discussed with respect to the possible role of the DIR as an anti-predator mechanism.

A specimen of brown trout, Salmo trutta, with a supernumerary dorsal fin located just posterior to the nape is documented from the Yarra River, Victoria, Australia.

Background: The function of the reticuloendothelial system is impaired in obstructive jaundice. The effects of obstructive jaundice on Kupffer cells and the influence of internal and external drainage are unclear. Aims: To study the effect of internal and external drainage on Kupffer cell phagocytosis and production of reactive oxygen species in rats with obstructive jaundice. Materials and Methods: Fifty male Sprague-Dawley rats weighing 300-350 g were randomly assigned to 4 groups: sham operation (SH, n = 11), obstructive jaundice by bile duct ligation and division (OJ, n = 12), internal drainage by choledochoduodenostomy (ID, n = 13) and external drainage by exteriorizing a biliary drainage tube at the nape (ED, n = 14) on day 7 after bile duct ligation. Kupffer cells were isolated by flow cytometric sorting 7 days later. The phagocytic function of the Kupffer cells was measured by flow cytometry using fluorescent microspheres (1.72 μm). The production of reactive oxygen species (ROS) was assayed by flow cytometry using dihydrorhodamine 123 (DHR) with phorbol myristate acetate (PMA) as an activator. Results: The phagocytic function was suppressed in OJ rats (20.8±7.4%) compared with SH rats (41.3±23.2%) (P=0.007). After drainage procedures, the depressed Kupffer cell function was reversed by ID (37.0±15.2%) (P=0.036), but not by ED (21.6±7.0%) (P=1.000). The release of ROS was higher in the OJ rats (1.35±0.36) than in the SH rats (0.98±0.09) (P=0.042). After drainage, the ROS production returned to normal levels in the ID rats (0.97±0.11) (P=0.032), but remained high in the ED rats (1.35±0.46) (P=1.000). Conclusion: Kupffer cell functions, including phagocytosis and release of reactive oxygen species, are impaired in obstructive jaundice. Internal biliary drainage, but not external drainage, causes recovery of Kupffer cell functions.

Comment on: Big cat attack: a case study.Wiens MB, Harrison PB. J Trauma. 1996; 40(5):829-31. Language: en

A series of experiments was carried out to investigate the ability of different types of stimulation to induce or intensify the “transport response” in 15-day-old rat pups when an initial stimulus, a pinch to the nape of the neck, produced either no transport response or only a very weak response. Rat pups given supplemental tactile stimulation, in the form of either an airpuff to the ventrum of a pinch to the tail, showed consistently stronger response intensities than when given only a pinch to the nape of the neck. Visual and auditory stimuli produced no increment in response intensities over those with only a dorsal pinch. Two additional experiments were carried out. The first investigated the ability of a puff of mist from an atomizer to induce a transport response in rats too old to show a strong response. The second investigated the induction of the transport response with supplemental stimulation in 19-day-old pups given haloperidol. Results suggest a nondopaminergic system subserving the response facilitation seen with supplemental tactile stimulation.

Play-fighting is often difficult to differentiate from inhibited or immature serious fighting because both may utilize many of the same behavior patterns. In the rat the two behaviors involve different targets of attack. During play-fighting, snout or oral contact is directed at the opponent's nape of the neck, whereas during serious fighting, male residents mostly direct their bites at the intruder's rump. Although similar to those used in serious fighting, the behavior patterns used during play-fighting are modified to achieve the different targets of attack. Even though the tactics of attack and defense appear more adult-like with increasing age, the playful targets persist well into adulthood.

Reconstruction in head and neck surgery has been greatly advanced with the use of the pectoralis major and trapezius myocutaneous flaps. Most surgical defects can be repaired with one of these flaps alone, or in conjunction with cutaneous flaps. Specific problems, however, occur that cannot be successfully reconstructed by these standard flaps. The traditional scalp flaps are cutaneous flaps. Use of these flaps is limited because of their shortened arc of rotation and accompanying forehead deformity. Three patients underwent reconstruction with a parietal occipital nape of neck myocutaneous flap. Its advantages include the following: large segments of hairless skin from the contralateral side of the neck can be used, an extensive arc of rotation and distance can be achieved with excellent vascularity in the overlying skin, and cosmetic results are superior. Angiographic studies were used to demonstrate the vascular pattern and supply to this flap. Cadaver dissections were performed to determine the pattern of distribution of the perforating vessels to the skin from underlying muscle.

Noxious pinch of the neck and the base of the tail can produce equipotent analgesia as measured by the tail flick method. However, noxious stimulation of the neck can supress pain responsiveness both at the site of stimulation and at sites remote from the stimulated area while noxious stimulation of the tail produces analgesia only at sites remote from the stimulated area. Thus, neck pinched animals are immobile and completely unresponsive to the noxious pinch whereas pinch to the base of the tail, which results in tail flick suppression, causes vocalization and well organized biting behavior directed at the pinched area. The analgesia elicited by noxious stimulation applied to both body regions is eliminated by spinalization, the administration of intermediate doses of barbiturates (30 and 45 mg/kg) and transection at the midcollicullar, but not more rostral, brain level. Concurrent with the elimination of the analgesic effect of noxious pinch on tail flick is the emergence of responses to noxious neck pinch with vocalization and intense motor reactions now elicited by noxious stimulation of the nape of the neck. These results indicate that different analgesic systems are activated by noxious tail and neck pinch both requiring the integrity of mesencephalic structures for their normal function. Furthermore, these systems can be distinguished by their ability to produce recurrent, inhibitory, supraspinal effects on nociceptive information originating at different body regions.

The binding of chlorophenoxyisobutyric (CPIB), tibric (TA) and nicotinic (NA) acids and CPIB ethyl ester (Clofibrate), TA and NA isopropyl esters (TAPE and NAPE) to human lipoproteins of low density of different classes (LDL 2 , LDL 1 and VLDL) and high density (HDL) were studied by equilibrium dialysis and Sephadex gel filtration. Clofibrate and TAPE bound strongly to lipoproteins, but their acids, CPIB and TA and also NA and NAPE, did not bind. In the same experimental conditions, Clofibrate and TAPE bound only weakly to human serum albumin (HSA) and CPIB bound to HSA with a K a of 3.3 × 10 5 M −1 for 1 site of high affinity. The Clofibrate and TAPE bound to lipoproteins did not dissociate either during dialysis or during filtration on Sephadex G 25. The binding percentage remained constant for all drug concentrations studied, and the molar ratio of bound drug rose linearly with increasing concentrations. This suggests that the interaction may be irreversible, and there is some evidence that binding may induce irreversible changes in the lipoprotein molecules. These results, and those already found in experiments made with three other drugs related to Clofibrate, lead to the proposal that in their interaction with lipoproteins, the phenyl groups are necessary and the esterification is contributory. The possible role of this interaction in the lipid-lowering effect of the drugs is discussed with special reference to their possible implication in lipoprotein synthesis within the intestinal and hepatic cells.

An experiment was performed on the effects of drugs on the labyrinthine muscular response in the bilateral deep nape muscles (M.rectus capitis posterior major et minor) of rabbit. These drugs such as antihistamin (i.e.of aminoether, phenothiazine), local anesthetica (i.e. cocaine, alcohol), sympathomimetic drugs (i.e.adrenalin, atropine.and pilocarpine), and interneuro. anal blocking agent (i.e.meprobamete), were infused into the tympanic cavity of normal and decerebrated rabbits, and anodal and cathodal galvanic stimulation was given to the animals upon the labyrinth (Nippon Koden MSE 2 Type stimulator), I measured voltage and amperage of the cathodal galvanic stimulation, when labyrinthine muscular response occured in the contralateral deep nape muscles for the purpose of determining the threshold of the stimulation.The obtained results are as follows:1.Both decerebrated and non-decerebrated rabbits showed labyrinthine muscule response even after drug-infusion as well as before.2.In the non-decerebrated rabbits, the threshold in the labyrinthine muscular reaction decr-eased after the infusion of pilocarpine or alcohol (in exciting stadium of alcohol).3.In the non-cerebrated rabbits the threshold increased after the infusion of restamia, cocaine, alcohol (in anesthetic stadium), adrenalin, contomin, and atropine.But it did not change after infusion of meprobamate.4.The decerebrated rabbits showed pronounced reactions than the normal after drug infusion, and the threshold in the decerebrated was lower than in the non-decerebrated.

Study of 2,901 clinically normal newborn infants showed the incidence of nevi of the nape and glabella and eyelids to be 266 per 1,000, whereas that of nuchal nevus alone was 234 per 1,000. Four familial patients were found, an incidence of 1.3 per 1,000. These nevae were not in creased significantly among 75 "abnormal" newborn infants studied.

Of various muscles of the rabbit in the natural position (e. g. nape, back, and forelimbs), the electromyographical studies were done and the changes in the posture were observed. The results obtained are as follows : 1. On the electromyogram, the spontaneous tonic discharges are obtained in the deep nape muscles (M. rectus capitis posterior major et minor, M. obliquus capitis superior), in the deep back (M. sacrospinalis) and the flixor and extensor of the forelimbs (M. articuloulnaris et Mm. anconaei), However they are not observed in the superficial muscles of the nape and the back (M. trapezius et M. splenius). 2. The postures are changed in labyrinthectomized rabbits following certain principles. 3. In following unilateral labyrinthectomy in the normal, but with removal of cerebrum and cervical nerves (C1∼C4) the tonic discharges are decreased mainly in thn deep nape and back, and the flexor of the forelimb contralaterally, and also in the extensor of the forelimb ipsilaterally. After the bilateral labyrinthectomy, the discharges disappear mostly. 4. Consequently the tonic discharges have relation to the labyrinthine muscle tonus and ch- anges of the posture.

On the normal and decerebrated rabbits, antihistamics (i.e. aminoether, ethylendiamine, phen- otliazine and monoamine), local anesthetics (i.e. cocaine and lalcohol), (i.e. adrenalin, pilocarpine, and atropine), and interneuronal blocking agent (i.e. meprobamate) are so introduced into the tympanic cavities, that the effect of the drugs upon their labyrinths could be studied clinically and electromyographycally. The obtained results were as follows: 1. Clinical findings: The spontaneous nystagmus to the untreated ear side was observed when the aminoether, cocaine, adrenalin and alcohol were introduced. When pilocarpine and alcohol were introduced spontaneous nystagmus to the treated side was observed. But by the application of the other drugs the spontaneous nystagmus was not observed. The head-deviation as the effect of antihistamin drug of aminoether, cocaine, adrenalin, and alcohol in anesthetic period, is shown with the infused ear downwards, and as the effect of pilocarpine and alcohol in stimulating period with the non-infusedd ear downwards. 2. Electromyographical findings: By the effect of antihistamin drug of aminoether, cocaine, adrenalin, and alcohol' in anesthetic period, the spontaneous discharges in the deep nape muscles of the non-infused ear side are decreased, and on the contrary are increased by pilocarpin and alcohol in stimulating period. By the other drugs the spontaneous, discharges in the deep nape muscles of the both sides are not changed. 3. The effect of the antihistamin drug of aminoether and local anesthetics upon the labyrinthine muscle tonus is remarkable, but of sympathetic drugs, i.e. adrenalin and pilocarpine'is slight. (autoreferat)

In rabbits, one suprarenal gland was extirpated through the lumbar route, without narcotizing. Forty to ninety days later the remaining gland was removed in quite the same manner; that is not after killing the animal on a blow on the nape. Epinephrine was esti-mated by the method of Suto-Kojima. No compensatory increase of the epinephrine load was found in the gland extirpated on the later occasion, contrary to the most previ-ous reports. Use of different procedures in extirpating the fellow glands, i.e. by the chirurgical operation at the first removal and by killing at once at the second, is chiefly responsible for the experimental results which had led the previous writers to an erroneous conception of the compen-satory increase of epinephrine. Further it must be warranted against the use of the method of Folin, Cannon and Denis, especially in such a kind of research. The reason is given in text.

It was found by the authors that in cases where 1% procaine solution was injected into nape muscles in normal subjects, vertiginous attacks as indicated by a sensation of sway of the body and “blacking out” were observed, accompanying with nausea and vomiting. The phenomenon mentioned above was evidently presented in case of applying the solution to deep nape muscles such as M. rectus capitis dorsalis major et minor, M. obliques atlantis and M. transversoocclpltalls. Whereas when the same procedure was carried out in superficial nape muscles such as M. trapezius and M. splenius, no sign of demonstrable disequilibrium nor any of disturbances of the vegetative reactions was observed. As to M. sternocleidomastoideus, it should be stressed here that when the procaine solution was applied to the muscle on one side and in a specific portion, i. e, in the origin of the muscle, the disequilibrium previously described was often observed, but it was not so marked as that in the case of deep nape muscles.By employing “Active head rotation test” devised by the authors as well as Romberg test, the authors were able to demonstrate the vertiginous attacks in the cases at hand as incoordination of the eye and head movements in case of active head rotation and a positive Romberg sign respectively.It is quite possible to say that the phenomenon mentioned above is considered to be caused on account of suddenly occured disturbances in the central nervous system, especially in the brain stem, which would be caused by ablation of impluses originating from y system in the muscles previously described, and that according to the investigations hitherto described, the ablation of impluses mentioned above should be presented by the injection of procaine solution mentioned.

Changes in head movements and the behaviours of various neck muscles which were caused by unilateral vestibular stimuli were studied electro-nystagmoraphycally in rabbits. the results obtained are as follows: I) When the head is deviated on the side of a non-stimulated ear, there immediately develops an increase in the tone of the perivertebral neck muscles of the same side. in head nystagmus the bilateral superficial anterior neck muscles which operated alternately head movements are inhibited on each side play the most important role. 2) the vestibular head movements are inhibited in consequence of a marked increase of tonus in the superficial nape muscles of the stimulated side under the control of the cerebellum.

Allergy characterized by delayed hypersensitivity was induced in populations of mice by injection, respectively, of Staphylococcus aureus and of tubercle bacilli. Eliciting doses of staphylococcal antigen or of old tuberculin antigen were injected subcutaneously into the nape of the neck of samples of these mice. A challenge dose of S. aureus was injected into the site of the eliciting injection, and the subsequent survival curves of the infecting staphylococci were determined by plate counts. Survival of the challenge staphylococci was significantly reduced only when the eliciting antigen was homologous with the inducing antigen. Thus induction and elicitation were specific, but the local resistance was nonspecifically effective against staphylococci.

The nape of the neck in small newborn infants remains relatively warm, compared with the exposed surface temperature of other body regions, in a heat-losing environment.

Examination was performed on rabbits, which were subdivided into the followings five groups: the intact, the unilaterally labyrinthectomized, the bilaterally labyrinthectomized, the decerebrated, the combinated of both decerebration and unilateral labyrinthectomy. Electric discharges were recorded in the muscles of the deep nape, the deep back and the fore limbs. Changings of the discharge in frequency were observed during angular acceleration of 90∼180- in a horizontal plane for 1∼2 seconds. The vestibulo-spinal reflex was discussed from the electromyographical point of view. 1. Labyrinthine muscular responses were observed in the deep nape and the deep back muscles, but not in the fore-limb. 2. In the deep nape and the deep back muscles of the intact and the decerebrated rabbits the electric discharges showed an increase in the muscles of the opposite side to rotatory direction, but a decrease in those of the same side during the accelerated period of rotation. During the decelerated period, however, the tendency of the muscular reaction was found to be reversed or to return to the state of the pre-stimulatory stage. The interval diagrams of discharges, observed in the decerebrated rabbit showed frequently smoothed curve as compared with those of the intact. 3. In the muscles of the intact side on the unilaterally labyrinthectomized animals, it was. difficult to record continuously the regular discharges, but phasic discharges were occasionally observed. The results of this experiment well support the contralateral innervation theory of the laby- rinthine muscular tonus. The electromyographical observations revealed that the muscular tonus was raised by the ampullopetal stimuli while it was inhibited by the ampullofugal.

JUSTIFICATIVA E OBJETIVOS: Lipoma é uma doença de crescimento progressivo que pode surgir em qualquer parte do corpo. O seu aparecimento na parte de trás do pescoço, especialmente quando é grande o bastante para causar restrição do pescoço, principalmente da extensão, é um desafio para os anestesiologistas sempre que precisam manejar as vias aéreas. Aqui, o papel do Airtraq® foi avaliado no movimento restrito do pescoço. RELATO DE CASO: Relatamos o caso de uma paciente selecionada para remoção cirúrgica eletiva de um lipoma enorme na nuca, medindo 14 x 12 cm, que apresentou dificuldade para assegurar a permeabilidade das vias aéreas por meio de laringoscopia convencional. Para resolver o problema, usamos com sucesso um dispositivo recentemente desenvolvido, o Airtraq®, que é um laringoscópio óptico para assegurar a via aérea. CONCLUSÃO: O Airtraq® pode ser usado para intubação eletiva em pacientes com movimentos restritos do pescoço. BACKGROUND AND OBJECTIVES: Lipoma is a progressively increasing disease which may appear anywhere in the body. Its appearance at the back of the neck, especially when it is large enough to cause restriction of neck extension, poses challenges to anesthesiologists in airway management whenever needed. This paper evaluates the role of Airtraq® in restricted neck movement. CASE REPORT: Case with a huge lipoma of 14 x 12 cm at the nape, and its surgical removal during an elective operation theatre posed difficulty in securing the airway by conventional laryngoscopy. To overcome the problem we successfully used a newly developed device, the Airtraq®, which is an optical laryngoscope for securing the airway. CONCLUSION: Airtraq® can be used for elective intubation in patients with restricted neck movements. JUSTIFICATIVA Y OBJETIVOS: El Lipoma es una enfermedad de crecimiento progresivo que puede surgir en cualquier parte del cuerpo. Su aparecimiento en la parte de atrás del cuello, especialmente cuando es bastante grande para causar su restricción, principalmente en la extensión, es un reto para los anestesistas que necesitan siempre manejar las vías aéreas. Aquí el papel del Airtraq® se avaluó en el movimiento restringido del cuello. RELATO DE CASO: Caso de una paciente seleccionada para la retirada quirúrgica electiva de un lipoma enorme en la nuca, que medía 14 x 12 cm, y que tuvo una dificultad para asegurar la permeabilidad de las vías aéreas por medio de una laringoscopia convencional. Para resolver el problema, ha utilizado exitosamente un dispositivo recientemente desarrollado, el Airtraq®, que es un laringoscopio óptico para asegurar la vía aérea. CONCLUSIONES: El Airtraq® puede ser usado para la intubación electiva en pacientes con movimientos restringidos del cuello.