Is the Assessment of Coping Capacity Useful in the Treatment of Obesity?

The purpose of this study was to determine if the assessment of coping capacity, as assessed by the Perception of Cognitive Structure, Emotional and Control Questionnaire (PASEC; Shalit, 1979a, 1979b, 1979c, 1981, 1982a, 1982b; Shalit & Carlstedt, 1984; Shalit et al., 1983), is useful in the treatment of obesity. Participants were 78 consecutive obese patients in a clinical treatment     

Intraspinal opiates for treatment of intractable pain in the terminally ill cancer patient

The discovery of opiate receptors and then their endogenous ligands in 1974 (Snyder et al., 1974) has elucidated a vast pharmacology of opiates providing a basis for their diverse clinical applications. With the awareness of quality of life as a primary goal in terminal cancer patients, widespread attention has been drawn to the direct delivery of long-term intraspinal analgesics to cancer patients for who all medical pain control regimens have failed (Coombs & Saunders, 1974). Intraspinal administration of opiates and nonopiate analgesics is not only appealing on theoretical grounds but provides a minimally invasive method to insure otherwise unobtainable pain relief while eliminating obtundation and systemic side-effects associated with conventional therapy (Cobb et al., 1984; Harbaugh et al., 1982; Leavens et al., 1982; Malone et al., 1985; Onofrie et al., 1981; Poletti et al., 1981). Although intraspinal opiates have been used in the treatment of postoperative and benign-pain syndromes (Asari et al., 1981; Cousins & Mather, 1984), in our discussion we review the basic science, current techniques and possible future improvements in spinal analgesia in the control of chronic cancer pain.     

Neural mechanisms in the pyrogenic and acute-phase responses to interleukin-1

It has become increasingly apparent over the past several decades that the hypothalamus, among other brain regions, plays an important part in the modulation of the immune system (reviewed in Korneva et al., 1985; Roszman & Brooks, 1985; Jankovic & Spector, 1986; Cotman et al., 1987). Since the hypothalamus also mediates the fever and various other acute-phase responses characteristic of the early stages of infection (reviewed in Hellon & Townsend, 1983; Blatteis, 1984, 1985; Cooper, 1987), it is possible that the localization within a common brain region of the controllers of several, different host defense reactions is not a happenstance, but represents a highly organized neuronal network serving to coordinate them. Indeed, pyrogenic, inflammatory, and immune responses do interact in the defense of the host against infection (reviewed in Dinarello, 1984). It is not yet known how immune responses are integrated centrally, but some data are available on the neural mechanisms controlling fever and certain components of the acute-phase reaction. The purpose of this paper is to review these briefly in the hope that a background can be provided against which features that may be common to neuroimmunomodulation and to the control of acute-phase reactions might be revealed.     

Intervention with disadvantaged parents of sick preterm infants

Infants born preterm are, as a group, at increased risk for a wide variety of later developmental problems (Kopp and Parmelee 1979), although many preterm infants do well (Hack et al. 1983; Saigal et al. 1984). The perinatal vulnerability, however, is amplified in disadvantaged families (Sameroff and Chandler 1975), increasing the likelihood of later emotional and cognitive difficulties (Werner and Smith 1977). A preventive intervention project was designed, therefore, that would provide and then evaluate the effectiveness of supportive home visitor services to parents of infants who were at double jeopardy, both biologically and socially--that is, sick preterm infants being reared by low-income parents. E. Baxter, K. Weiler and I hypothesized that if intervention could increase mothers' involvement and level of responsive interactions with their children, that increased maternal commitment and responsiveness to the infant would act as a protective factor ameliorating or preventing later problems in the child (Beckwith and Cohen 1984; Werner and Smith 1982).     

Neuroendocrine effects of ovine corticotropin-releasing hormone in panic disorder patients

A number of neuroendocrine abnormalities have been reported in panic disorder patients: the most extensively studied being disturbances of hypothalamic-pituitary-adrenal function (Curtis et al. 1982; Leiberman et al. 1983; Uhde et al. 1988). The recent sequencing and synthesis of corticotropin-releasing hormone now allows direct testing of pituitary responsivity to this neuropeptide in affective and panic disorder patients (Holsboer et al. 1984; Gold et al. 1986; Roy-Byrne et al. 1986; Holsboer et al. 1987; Risch et al. 1988). We report the effects of intravenously administered ovine corticotropin-releasing hormone (0.03 micrograms/kg) on plasma concentrations of adrenocorticotropin hormone (ACTH) and cortisol in a small group of panic disorder patients and age- and sex-matched normal controls.     

Calcium-promoted translocation of protein kinase C to synaptic membranes: relation to the phosphorylation of an endogenous substrate (protein F1) involved in synaptic plasticity

The translocation of protein kinase C between membrane and cytosol has been implicated in several cellular processes (Kraft and Anderson, 1983; Wooten and Wrenn, 1984; Akers et al., 1985, 1986; Hirota et al., 1985; Wolf et al., 1986). We desired to identify potential trigger mechanisms underlying the translocation of protein kinase C activity to neural membranes following the synaptic plasticity observed after long-term potentiation (LTP; Akers et al., 1986). Takai et al. (1979) have suggested an important role for calcium in protein kinase C translocation; we have therefore studied the effects of Ca2+ on both the translocation of protein kinase C activity and the in vitro phosphorylation of its endogenous substrate, protein F1, in rat hippocampal synaptosomes. Since identical free Ca2+ levels were maintained in subsequent assays of synaptosomal membranes (SPM) and cytosol preparations, alterations in endogenous enzyme activity and in vitro phosphorylation were due to the Ca2+ present during treatment of synaptosomes, and not to the Ca2+ present during assays of enzymatic activity. This afforded the opportunity to relate directly such enzyme translocation to endogenous substrate phosphorylation. The major findings were as follows: 1. Following treatment of synaptosomes with Ca2+, protein kinase C activity in synaptic membrane and protein F1 in vitro phosphorylation were elevated in a dose-dependent manner. 2. The greatest increment in membrane protein kinase C activity and protein F1 in vitro phosphorylation occurred when Ca2+ was increased from 0.1 to 1.0 microM. Maximal levels of enzyme activity were seen following treatment with 10 microM Ca2+, and minimum levels were observed following treatment with EGTA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postmitotic, postmigrational expression of tyrosine hydroxylase in olfactory bulb dopaminergic neurons

The developmental expression of tyrosine hydroxylase (TOH) was studied in a large, specific population of dopaminergic (DA) neurons in the main olfactory bulb (MOB) of the rat. These DA neurons comprise an anatomically distinctive population that has been well characterized in the adult hamster (Davis and Macrides, 1983) and rat (Halasz et al., 1981; Baker et al., 1983, 1984). We addressed a basic question in developmental neurobiology: What factors regulate the expression of neuronal transmitter phenotype during development? Olfactory bulb DA neurons are born in the ventricular and subependymal zones and migrate through all intervening layers to the most superficial layer in the bulb (Altman, 1969; Bayer, 1983). The time of TOH expression in these neurons was determined using immunohistochemistry and light microscopic image-analysis techniques. The results indicate that TOH phenotype is not expressed when the cells are born in the subependymal zone nor during their migration to the periglomerular region but only after they reached their final destination, the glomerular layer. This suggests that epigenetic factors associated with the glomeruli initiate the expression of the key transmitter synthesizing enzyme in these neurons. Primary olfactory neurons in the nasal epithelium project exclusively to glomeruli of the MOB; removal of this input in adult rats (Kawano and Margolis, 1982; Baker et al., 1983, 1984), mice (Nadi et al., 1981; Baker et al., 1983), dogs (Nadi et al., 1981), and hamsters (Kream et al., 1984) appears to down-regulate the expression of the TOH in periglomerular cells. The present results suggested that the input from the primary olfactory nerve is also necessary for the initial expression of the TOH phenotype. In support of this notion, we found that lesions of the olfactory nerve during the first postnatal week caused a significant reduction in the number of TOH-positive juxtaglomerular neurons in the following weeks. Thus, the olfactory nerve appears to be necessary for both the initiation and maintenance of TOH expression in olfactory bulb neurons. These findings suggest that specific cell-cell interactions play a key role in CNS neuronal transmitter phenotype regulation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Creatine kinase and enolase: intracellular enzymes serving as markers of central nervous system damage in neuropsychiatric disorders.

A frequently used method to assess cellular dysfunction and damage in humans is to document the presence of uniquely intracellular proteins in extracellular spaces. Thus, increased plasma levels of transaminases generally reflect hepatocellular damage (Lieber 1978), increases in the cardiac fractions of creatine kinase (CK, or CPK for creatine phosphokinase) or lactate dehydrogenase (LDH) are diagnostic for myocardial infarction (Armstrong et al. 1979; 1982), and increases of skeletal muscle fractions of CK may indicate myopathy (Goto 1974; Ford 1984). Similarly, a number of enzymes and proteins serve as tumor markers in a variety of malignant cancer (e.g., Concannon et al. 1974; Foti et al. 1977).     

Spinal cord segments containing key elements of the central pattern generators for three forms of scratch reflex in the turtle

The immobilized, low-spinal turtle produces 3 forms of the fictive scratch reflex in response to tactile stimulation of specific sites on its body surface (Robertson et al., 1985). We used complete transections of the spinal cord at different rostrocaudal levels to reveal the minimum length of spinal cord sufficient to produce each scratch form. Additional transections revealed the progressive loss of elements of the motor pattern and the eventual loss of rhythmogenesis. We have identified, therefore, spinal cord segments containing key elements of each scratch form's central pattern generator (CPG). The turtle spinal cord consists of 8 cervical segments (C1-C8), 10 dorsal segments (D1-D10), 2 sacral segments (S1, S2) and about 16 caudal segments (Ca1-Ca16; Kusuma et al., 1979). The cell bodies of motor neurons innervating the hindlimb muscles are located in the hindlimb enlargement, segments D8-S2 (Ruigrok and Crowe, 1984). The receptive field for the rostral scratch is innervated by segments D3-D6; the pocket scratch receptive field is innervated by segments D6-D8; the caudal scratch receptive field is innervated by segments S2, Ca1, and more caudal segments (Mortin and Stein, 1985). A rostral scratch motor pattern could be produced with as few as 5 or 6 segments, i.e., segments D5-D9 or D3-D8. The anterior 3 segments of the hindlimb enlargement, D8-D10, could produce a pocket scratch motor pattern. A single segment, either D7 or D8, is capable of rhythmogenesis in response to stimulation of sites in its part of the pocket receptive field. A caudal scratch motor pattern could be produced by D8-End (the hindlimb enlargement and more caudal segments). The posterior 40-80% of the hindlimb enlargement is not necessary for the production of a rostral or pocket motor pattern. The anterior segment of the enlargement is necessary for the production of a normal caudal scratch motor pattern. Key elements of the CPG for each of the 3 scratch forms reside in segments D7-D10. The pattern-generating capacity of the anterior half of the hindlimb enlargement is greater than the posterior half; such an asymmetric distribution of pattern-generating elements in the enlargement of the spinal cord has been described for cat scratching (Deliagina et al., 1983). These results are consistent with the hypothesis that the CPGs producing different motor patterns for the hindlimb share neuronal elements (Grillner, 1981; Robertson et al., 1985; Currie and Stein, 1988, 1989).     

The use of astrocytes in culture as model systems for evaluating neurotoxic-induced-injury.

The prevailing thought that astrocytes function predominantly as passive metabolic or even physical support for neurons has faded over the last 20 years. Today these stellar shaped cells are credited with an expanded role, playing key functions in CNS development, homeostasis, and pathology. In probing their expanded roles, primary astrocyte culture systems have proven to be an indispensable tool. Astrocytes have been implicated in both a defensive and facilitatory capacity for many toxic injuries. Evidence for a protective role of astrocytes in modulating CNS toxicity is afforded by observations that the toxicity of glutamate to cortical neurons is diminished upon astrocytic enrichment of the cell culture (Rosenberg and Aizenman, 1989). In cultures of rat cerebral cortex in which astrocyte proliferation is stringently suppressed, glutamate neurotoxicity occurs at low glutamate concentrations similar to those which are normally found in the extracellular space in the hippocampus. In the presence of excess astrocytes, concentrations of glutamate one-hundred fold higher are required to produce equivalent neurotoxicity (Rosenberg and Aizenman, 1989). Astrocytes can facilitate the action of neurotoxins via a modulating process which takes place within the astrocyte or by a direct cytotoxic effect. Whereas primary astrocyte cultures remain unaffected by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; Marini et al., 1989), they function prominently in the selective destruction of dopaminergic neurons of the nigrostriatal pathway in humans, other primates and rodents (Davis et al. 1979; Langston et al., 1983; Burns et al., 1983; Langston et al., 1984; Heikkila et al., 1984; Jarvis and Wagner, 1985). Thus, while MPTP by itself is not toxic to cerebellar cells in co-culture with cerebellar astrocytes, MPTP is toxic to the granule cells (Marini et al, 1989). This is thought to be due to an astrocyte-mediated conversion of MPTP to its highly polar and toxic metabolite, 1-methyl-4-phenylpyridinium ion (MPP+; Chiba et al. 1984). There is compelling evidence that astrocytes respond directly or indirectly to a number of other neurotoxins. Direct cytotoxic effects on astrocytes constitute the major morphologic feature in hyperammonemia (Norenberg, 1981), a condition implicated as an etiologic factor in several CNS disorders. In addition, a predisposition of astrocytes for methylmercury uptake (Aschner et al., 1990 a,b) offers a possible explanation for the observed neurotoxicity of this heavy metal, since a direct toxic effect on astrocytes would result in failure of astrocyte homeostatic functions, indirectly resulting in neuronal impairment, injury and death.     

Interaction sequences in families of psychiatrically hospitalized and nonpatient adolescents

A KEY theme running through competing views of family influences upon adolescent development is that of directionality, on two levels: influences within the flow of family interaction; and influences from family processes to individual adolescent development. In this paper our focus is upon the first level, intrafamilial sequences within families. More specifically, we study links between psychiatric impairment in adolescence and developmentally relevant parent-child and parent-parent sequences. This report extends a previous investigation (Hauser et al. 1984), which described our new family coding system and first correlational findings. We now study the flow of interactions within these families. Although there has been much recent empirical research in adolescent psychosocial development (e.g., Redmore and Loevinger 1979; Loevinger 1976; Adams and Fitch 1982; Hauser et al. 1984), one important area has received less attention--the relationship between developmentally relevant family processes and psychiatric disturbance during adolescence.     

Defense behavior and coping in an autistic savant: the story of Temple Grandin, PhD.

The causal factors in the behaviorally defined syndrome of autism remain unclear, although the past decade has brought to bear two significant developments that shape our view of the disorder. The first of these developments is a growing body of biomedical research that indicates there are multiple etiologies associated with the disorder. This research has allowed for the formation of subgroups based upon neuroanatomical, neurobiological, and neurophysiological abnormalities (Damasio 1984; Piggot 1979; Ritvo et al. 1990). The second is neuropsychological research indicating that the socioemotional deficits are primary to the disorder and may underlie much of the behavioral symptomatology (Fein et al. 1986). These areas of concern undoubtedly have enhanced our understanding of the disorder, yet in their achievements they may too easily absorb what we know about autistics who experience a chronic state of physiological hyperarousal, evidence of which has been found in neurophysiological studies (Delius 1967; Hutt et al. 1965), neurochemical studies (Lake et al. 1977), psychopharmacologic studies (Ratey et al. 1987a), and behavioral studies (Kinsbourne 1980; Kootz et al. 1982; Tinbergen and Tinbergen 1972; Zentall and Zentall 1983). These individuals, perhaps constituting a subgroup of their own, experience an inner state of disorganization that markedly impairs their functioning (Sands and Ratey 1986).     

Adreno-leukodystrophy (adreno-testiculo-leukomyelo-neuropathic-complex)

We have learned much about adreno-leukodystrophy (ALD) since the first case report by Siemerling and Creutzfeld [1923]. Many aspects of this disease, however, are still enigmatic and worthy of investigation (see Pathogenesis). We now realize that ALD is a constellation of clinical and pathologic presentations, all of which presumably are caused by an X-linked genetic defect in the handling of fatty acids [Migeon et al. 1981, Ogino and Suzuki 1981, Singh et al. 1984]. At the present time, and for the sake of this discussion, adreno-leukodystrophy is subdivided into 5 major clinical types: classical, X-linked juvenile ALD; X-linked adult ALD; adrenomyeloneuropathic variant (AMN); female ALD; and neonatal ALD. A sixth type, which has only pathologic and pathogenetic relevance, is the fetal form [Powers et al. 1982]. Patients may have clinical or subclinical involvement of only one organ system (e.g., adrenal) or they may have any combination of adrenal, testis, brain, spinal cord, and peripheral nerve disease [O'Neill et al. 1981]. The most common type is the classical juvenile form, followed by the AMN variant. X-linked adult ALD is uncommen and female ALD is rare. The precise nosologic placement of the neonatal form is still debated and will be discussed more fully below. Although satisfactory treatment of central nervous system demyelination in ALD and system degeneration in AMN awaits a better understanding of their pathogenesis, we are now able to control this disease complex by carrier identification and genetic counseling or by in utero detection and therapeutic abortion [Moser et al. 1984].     

A comparison of autistic syndromes with and without associated neurological problems

Conclusions The findings show that autistic syndromes with and without associated neurological deficits are remarkably similar in terms of severity and type of autistic symptoms, IQ, and sex distribution. Children with an associated neurological disorder tended to have had autistic features from birth, but this may have been an artifact resulting from the closer clinical observation that many would have received because of their medical problems. Findings from related studies have also shown that autistic syndromes with and without neurological deficits do not differ with respect to urinary homovanillic acid levels (Garreau et al., 1980), dihydroxy-phenylacetic acid levels (Landgrebe & Landgrebe, 1976), auditory evoked potentials (Martineau, Garreau, Barthelemy, Callaway, & LeLord, 1981) or response to vitamin B₆ administration (LeLord et al., 1981; Martineau et al., 1981). This research was supported by CNRS (ERA N-697) “Biology and Neuropsychiatry,” INSERM 650.34 and Social Security 1982. We wish to thank Mrs. Barre, Mrs. Lardeux, and Mrs. Crespin for their technical work.     

Relapsing polychondritis with multifocal neurological abnormalities

A sixty-five year old woman developed relapsing polychondritis with three of the diagnostic criteria established by McAdam et al. (1976), namely bilateral auricular chondritis, ocular inflammation and both cochlear and vestibular dysfunction. Many authors have mentioned other neurological symptoms including unilateral facial weakness. This patient is the first case described with bilateral facial weakness and cerebral manifestations. Relapsing polychondritis, an uncommon, recurrent, inflammatory disorder affecting the cartilaginous tissues of the body (Jaksch-Wartenhorst, 1923; Herman, 1981), is regularly associated with audiovestibular dysfunction (Bollet et al., 1969; Cody et al., 1971; McAdam et al., 1976; Ridgway et al., 1979). McAdam et al. (1976) and Ridgway et al. (1979) have mentioned other neurological symptoms including unilateral facial weakness. We recently observed a patient with polychondritis and multifocal neurological abnormalities. We believe this is the first case described with bilateral facial nerve palsy and with cerebral manifestations.     

Heterogeneous distribution of neurotensin-like immunoreactive neurons and fibers in the midbrain periaqueductal gray of the rat

The midbrain periaqueductal gray (PAG) has been shown to be a site where various manipulations induce pain suppression. Recent physiological evidence (Behbehani and Pert, 1984; Behbehani et al., 1987) suggests that neurotensin has pronounced physiological actions in PAG and effects pain suppression. We have performed immunohistochemical studies in order to determine the magnitude and distribution of neurotensin-like immunoreactive (NT-IR) cell bodies and fibers in PAG. NT-IR cell bodies were common throughout PAG, although there were more in the caudal than the rostral half. NT-IR neurons were much more numerous in the ventral than the dorsal half of PAG, and some appeared to be located within the dorsal raphe nucleus. The pattern of NT-IR fibers was analyzed with the aid of image enhancement/analysis and densitometry. The fibers were found to be heterogeneously distributed, being most heavily concentrated in the region adjacent to the cerebral aqueduct in the caudal two-thirds of PAG. The distribution of NT fibers closely matches sites where exogenously applied NT elicits long-lasting excitation of PAG neurons (Behbehani et al., 1987). Based on the known physiological and behavioral actions of NT in PAG, the present anatomical results suggest that NT acts on elements located predominantly in the medial and ventrolateral parts of PAG. Neurons activated by NT may project directly to the nucleus raphe magnus and adjacent ventral medulla (Behbehani and Pert, 1984) to activate neurons that project to the spinal cord and modulate nociceptive circuits.     

The role of the cytoskeleton in neuromuscular junction formation

The cytoskeleton plays a vital role in neuromuscular junction (NMJ) formation. It is responsible for shaping synaptic membrane into folds opposed to presynaptic active zones and anchoring acetylcholine receptors (AChRs) to the crest of the junctional folds. Acetylcholine receptors (AChRs) associate with the actin cytoskeleton, the disruption of which affects spontaneous and agrin-induced AChR clusters (Prives et al., 1982; Connolly, 1984; Peng and Phelan, 1984; Bloch, 1986; Dai et al., 2000). How AChRs are tethered to the actin cytoskeleton remains unclear.     

Rodents rely on Merkel cells for texture discrimination tasks

The cutaneous somatosensory system contains multiple types of mechanoreceptors that detect different mechanical stimuli (Johnson, 2001). These stimuli, either alone or in combination, are ultimately interpreted by the brain as different aspects of the sense of touch. Psychophysical and electrophysiological experiments in humans and other mammals implicate one of these mechanoreceptors, the Merkel cell/neurite complex, in two-point discrimination and the detection of curvature, shape, and texture (Johnson and Lamb, 1981; Johnson et al., 2000; Johnson, 2001). However, whether Merkel cell/neurite complex function is required for the detection of these stimuli is unknown. We genetically engineered mice that lack Merkel cells (Maricich et al., 2009; Morrison et al., 2009) to directly test the hypothesis that Merkel cell/neurite complexes are necessary to perform these types of sensory discrimination tasks. We found that mice devoid of Merkel cells could not detect textured surfaces with their feet while other measures of motor and sensory function were unaffected. Interestingly, these mice retained the ability to discriminate both texture and shape using their whiskers, suggesting that other somatosensory afferents can functionally substitute for Merkel cell/neurite complexes in this sensory organ. These findings suggest that Merkel cell/neurite complexes are essential for texture discrimination tasks involving glabrous skin but not whiskers.     

Book review

Johnson, D.J., & Blalock, J.W. (Eds.) (1987). Adults with Learning Disabilities: Clinical Studies. Orlando, FL, Grune & Stratton. ISBN 0-8089-17951