Regional cerebral blood flow correlated with flashback intensity in patients with posttraumatic stress disorder.

BACKGROUND: Nuclear imaging studies have examined cerebral blood flow (rCBF) in subjects with posttraumatic stress disorder (PTSD) using symptom evocation paradigms. To date, no such studies have investigated rCBF as related to subjects' reports of flashback intensity. METHODS: Subjects with varying traumatic histories and longstanding PTSD were studied using [15O]-H2O positron emission tomography with an auditory script of their traumatic event. Eight subjects had three resting scans followed by their script and additional scans. Heart rate responses as well as the presence of flashbacks and their intensity were recorded. rCBF was correlated with flashback intensity in each subject's scan. Combined analysis of all subjects' data yielded common regions related to the flashback experience. RESULTS: rCBF correlated directly with flashback intensity in the brainstem, lingula, bilateral insula, right putamen and left hippocampal and perihippocampal, somatosensory and cerebellar regions. Inverse correlations with rCBF were found in bilateral dorsolateral prefrontal, right fusiform and right medial temporal cortices. CONCLUSIONS: This study correlated flashback intensity and rCBF in a group of patients with chronic PTSD suggesting involvement of brainstem, and areas associated with motor control, complex visual/spatial cues and memory.

Regional brain activity during transient self-induced anxiety and anger in healthy adults.

BACKGROUND: Several studies have demonstrated that transient self-induced sadness activates anterior paralimbic structures. To further examine the specificity of these findings and the neural substrates involved in anger and anxiety, we studied the neural correlates of the induction of anxiety and anger in healthy adults. METHODS: We used H2(15)O and positron emission tomography (PET) to measure regional cerebral blood flow (rCBF) in 16 healthy adults during the induction of transient anxiety, anger, and neutral emotions. Subjects achieved differential emotions by recalling prior life events while viewing affect-appropriate faces. RESULTS: Both the anxiety and anger conditions were associated with increased normalized rCBF in left inferior frontal and left temporal pole regions and decreased rCBF in right posterior temporal/parietal and right superior frontal cortex, compared to the neutral induction. Additionally, compared to neutral induction, anxiety was associated with increased rCBF in the left anterior cingulate and cuneus and decreased rCBF in right medial frontal cortex, while the anger induction was uniquely associated with increased rCBF in right temporal pole and thalamus. CONCLUSIONS: Self-generated transient states of anxiety and anger are associated with both overlapping and distinct regional brain activity patterns and provide a template for further dissection of specific components of normal and pathologic emotions.

The 7SL RNA homologue of Trypanosoma brucei is closely related to mammalian 7SL RNA.

In eukaryotes, protein translocation across the endoplasmic reticulum is mediated by a signal recognition particle, a small ribonucleoprotein (RNP) containing 7SL RNA. We have cloned and sequenced the gene coding for the Trypanosoma brucei 7SL RNA homologue and found that its sequence shows the highest degree of similarity to the human 7SL RNA sequence. In keeping with the prototype secondary structure of eukaryotic 7SL RNA, the trypanosome 7SL RNA secondary structure can be folded into four domains. The 7SL RNP, which sediments at approximately 11S on sucrose density gradients, was partially purified using column chromatography. A particle containing a 76-nucleotide-long RNA co-purified with the 7SL RNP; however, these particles did not co-fractionate by non-denaturing polyacrylamide gel electrophoresis.

Bone and joint manifestations of hypothyroidism.

Hypothyroidism is frequently accompanied by musculoskeletal manifestations ranging from myalgias and arthralgias to true myopathy and arthritis. A case is presented in which an arthropathic process in the hip was the isolated finding in a young man who was severely hypothyroid. Previous literature on bone and joint manifestations of hypothyroidism is reviewed, with emphasis on cases where such manifestations were the presenting symptoms of thyroid dysfunction. Most cases of arthropathic changes in adult-recognized hypothyroidism involved the knees and hands, while the hip and the epiphysis of the femoral head appear more commonly involved in children. Thyroid hormones have known effects at the cellular level on proliferation and differentiation of bone and cartilage. The hypothyroid state appears to induce abnormalities in these tissues, which result in such clinical manifestations as epiphyseal dysgenesis, aseptic necrosis, possibly crystal-induced arthritis, and an arthropathy characterized by highly viscous noninflammatory joint effusions primarily affecting the knees, wrists, and hands. Neuropathic and myopathic symptoms accompanying hypothyroidism may manifest as joint region abnormalities when in fact there is no underlying arthropathy.

Noradrenergic alpha-2 receptor agonists reverse working memory deficits induced by the anxiogenic drug, FG7142, in rats.

Performance on working memory tasks, a measure of prefrontal cortical function, is impaired by exposure to mild stress as well as the anxiogenic drug, FG7142. Previous studies have shown that like stress, FG7142 increases catecholamine release in the prefrontal cortex (PFC) and that high levels of dopamine (DA) D(1) and norepinephrine (NE) alpha-1 receptor stimulation underlie the FG7142-induced cognitive impairment. Both the FG7142-induced DA turnover and working memory deficit can be blocked by pretreatment with the nonselective NE alpha-2/imidazoline I1 receptor agonist, clonidine. The present study examined the alpha-2 adrenoceptor subtype underlying this reversal in FG7142-induced working memory deficits by comparing the efficacy of clonidine with the more selective alpha-2A adrenoceptor agonist, guanfacine. The anxiogenic drug, FG7142 (0, 10, 20, or 30 mg/kg), dose-dependently impaired delayed alternation performance. Clonidine pretreatment (0.1 mg/kg, 30 min prior to FG7142) partially reversed the FG7142-induced impairment while guanfacine pretreatment (0.11 mg/kg) completely blocked the FG7142-induced impairment. Neither clonidine nor guanfacine had any effect on performance when administered alone. This study suggests that stimulation of the NE alpha-2A receptor subtype is sufficient to ameliorate the cognitive deficit induced by FG7142. Clonidine's sedative and hypotensive side effects limit its therapeutic usefulness; however, selective alpha-2A receptor agonists may be effective in treating prefrontal cognitive deficits in stress-related neuropsychiatric disorders with fewer side effects.

Pulmonary manifestations of scleroderma.

Scleroderma is a severe systemic collagen vascular disease of unknown cause characterized by marked vascular and connective tissue abnormalities. The lungs are commonly involved in scleroderma, ranking only behind the skin, the peripheral vasculature, and the esophagus in frequency of organ involvement. Respiratory symptoms are, in a very few cases, the presenting manifestation of the disease. Abnormalities of pulmonary function in affected patients include a restrictive ventilatory defect, air flow obstruction, and a depressed diffusing capacity for carbon monoxide, which may be an isolated early finding. Interstitial lung disease and honeycombed lung are the most common pulmonary parenchymal abnormalities seen on chest radiographs. Enlargement of the cardiac silhouette and pulmonary artery due to scleroderma-induced pulmonary vascular disease is also noted. High-resolution computed tomography (HRCT) apparently is a sensitive, potentially useful technique for detecting occult interstitial lung disease in patients with scleroderma. Bronchoalveolar lavage usually shows an increase in total cell count and in the percentage of granulocytes; occasionally, there is a predominantly mononuclear (lymphocytic) cell alveolitis. Premortem and postmortem studies reveal two predominant lung lesions: (1) interstitial lung disease and (2) pulmonary vascular disease. Pulmonary vascular disease may occur in the absence of interstitial lung disease, particularly in patients with limited, as opposed to diffuse, scleroderma. The overall mortality rate in scleroderma is 50% at 7 years, and pulmonary complications are the major cause of death. No prospective, well-controlled studies have established that treatment alters the natural course of pulmonary disease in patients with scleroderma. Both D-penicillamine and cyclophosphamide have shown promise for treating patients with interstitial lung disease, and nifedipine may be useful for treating patients with early pulmonary vascular disease.

Mental retardation and adult women's perceptions of adolescent sexual abuse.

This study examined the effect of mental retardation and an adolescent girl's behavior on adult women's perceptions of sexual abuse and the girl's responsibility. Subjects were 288 women, age 18 to 33, who were randomly assigned a vignette describing a sexual encounter between an adolescent girl and boy. Girl's diagnosis (mentally retarded or nonretarded), boy's diagnosis (mentally retarded or nonretarded) and girl's behavior (encouraging, passive, or resisting) were experimentally manipulated. Factor analysis of responses yielded three factors: girl's responsibility, boy's abusiveness, and parents' responsibility. Results indicate that subjects perceive the girl's responsibility differently among girls with and without mental retardation. Regardless of her behavior, subjects perceive the girl as bearing little responsibility when she is retarded. However, when she is nonretarded, she bears more responsibility when she is encouraging than when she is passive or resisting, and she bears greater responsibility when she is passive than when she is resisting. Also, when the girl is encouraging, the boy's perceived sexual abusiveness is less when he is mentally retarded than when he is nonretarded. Finally, parents are assigned greatest responsibility when the girl is passive, regardless of her diagnosis.

Psychotherapy as an approach to special education prevention: perceptions of student behavior.

This study investigated the impact of one year of psychotherapy, used in an attempt to avoid special education referral, on teachers' and psychotherapists' perceptions of student disruptiveness and withdrawal. Results indicated that psychotherapists perceived improvement in both types of behavior, while teachers did not. Possible reasons for this perceptual difference are discussed.

Adolescents with mental retardation: perceptions of sexual abuse.

Reactions of nonretarded female undergraduates to sexually coercive situations in which neither, one, or both protagonists had mental retardation were examined. Results indicated that retardation affected perceptions of both responsibility and harm. Implications for the education of mental health professionals about the emotional needs of individuals with retardation are discussed.

Art and trauma.

The authors of this paper attempt to show that 'the art of trauma', because of its indirect, unaestheticised and dialogic nature, may be the only possible medium for effective representations of trauma. The real witnessing presence created in the art of trauma can act as an antidote to the annihilation of the internal 'other' that occurs in the traumatic experience and to the resulting absence, which both constitutes the core of trauma and precludes its representation. Important elements of the art of trauma are illustrated using the work of Paul Celan, Anselm Kiefer, Claude Lanzmann, Art Spiegelman, and Anne-Marie Levine and texts by Aharon Appelfeld. Examining more closely what Holocaust survivors say in their testimonies, the authors contend that survival itself should be considered as a type of art of trauma when it is made possible by a creative comprehension of reality analogous to that which characterises more conventional forms of the art of trauma. The authors proceed to explore both the possible limits to the extent that trauma may be represented and the continuous struggle involved in attempting to 'know' trauma. They also discuss how art dealing with trauma may circumscribe a double locus: one of witnessing as well as one of emptiness or execution.

Pyroglutamic acid. Non-metabolic formation, function in proteins and peptides, and characteristics of the enzymes effecting its removal.

The formation of pyrrolidone carboxylic acid (PCA, pGlu) during protein biosynthesis is discussed. Studies are summarized which demonstrate that PCA is formed during the later stages of biosynthesis at the terminal phases of translation or as a post-translational event, just prior to cellular secretion of protein with amino-terminal PCA. Of the studies cited, the most convincing evidence suggests that PCA is derived from glutamine. Enzymes which selectivity remove PCA from the N-terminus, and of benefit in amino-acid sequence analysis, have been isolated and shown to have a ubiquitous distribution in various animal and plant cells. The investigations which lead to the isolation o these enzymes and the procedures for their use in removing amino-terminal PCA from proteins, are described. Finally, the biologic function of PCA and the effects of its chemical modification are discussed using the neuropeptide. Thyrotropin Releasing Factor (TRF) as a specific example.

Characterization of monoclonal IgG cryoglobulins: fine-structural and morphological analysis.

The morphology of the amorphous, gelatinous, and crystalline varieties of monoclonal IgG cryoglobulins was analyzed by light and transmission and scanning electron microscopy. Each cryoglobulin had a characteristic fine structure that correlated with its gross morphology. Transmission electron microscopy showed that the amorphous precipitates were random and disorganized molecular clumps. In contrast, cryogels were thin-walled, well-organized, and hydrated strawlike clusters, whereas cryocrystals formed tightly compacted, highly structured molecular clusters. Crystals that formed in blood produced rouleaux, and analysis by scanning electron microscopy indicated that the crystals could form thick-walled, branching, macromolecular nets that could physically trap cells. The morphological properties provided visual impressions by which cryoglobulins could cause clinical disease secondary to vascular occlusion produced by self-associated IgG cryoglobulin molecules.

Immunological and structural properties of human monoclonal IgG cryoglobulins.

Structural and immunological properties were determined for sixteen IgG and one Bence-Jones, human monoclonal cryoglobulins. The heavy chain subclass percentages were 47% IgG1, 14% IgG2 and 29% IgG3, and were different from previously reported distributions of myeloma proteins. In addition, 69% (eleven out of fifteen) of the cryoglobulins and 100% (seven out of seven) of the IgG1 cryos contained type lambda light chains. Electrofocussing of the cryoproteins by analytical liquid gradient column showed the isoelectric points to be included in the range of pH 6.3--8.9. The pI of six light chains and five out of six heavy chains were at acidic and slightly basic pH, respectively. The pI of the intact cryoglobulins were thus close to those of their constituent heavy chains. Six out of seven of the heavy chains were subjected to automated Edman degradation and were classified as containing vH-i or vH-ii variable region subgroups on the basis of their blocked amino termini. One type lambda light chain was unusual in that it contained an amino terminal sequence initially described in an amyloid fibril protein and is the first instance in which light chains with this sequence have been isolated from IgG. The data support the notion that the cryoglobulins are IgGs with unique structural and immunological properties which separate them from non-cryoprecipitable IgGs.

Idiotypic relatedness of human monoclonal IgG cryoglobulins.

The serological relatedness of the idiotypic (ID) determinants of one type lambda light chain dimer and fifteen monoclonal IgG cryoglobulins were assayed. Rabbits were immunized with 9/15 IgG cryoglobulins, and twenty-three antisera were obtained and absorbed to render them specific for the ID determinant of the immunizing IgG cryoglobulin. By use of haemagglutination-inhibition, cross-reactivity was detected among five cryoglobulins. This was localized to the Fab region of the IgG, was not related to identity of the variable region subgroups of the heavy and light chains of the cross-reactive cryoglobulins, and was not detected in eighteen non-cryoprecipitable IgG myeloma proteins. The serological relatedness of the ID determinants suggests that a subset of IgG cryoglobulins may possibly have similar variable region structures and/or antigenic specificities.