Charcot-Marie-Tooth phenotype produced by a duplicated PMP22 gene as part of a 17P trisomy-translocation to the X chromosome

The Charcot-Mane-Tooth disease type 1A (CMTlA) phenotype is most often associated with a 1.5 megabase (mb), tandem duplication of chromosome 17 band p12 (17˜12). The prevailing hypothesis is that the demyelinating neuropathy results from a dosage effect of the peripheral myelin protein gene PMP22 which is included within this duplication. We present a patient with clinical and electrophysiological features ofCMTlA in whom an extra PMP22 gene resulted from a rare unbalanced translocation of 17p to the X chromosome. This finding further supports the hypothesis of gene dosage as the basis for CMTlA. More-over, this case highlights the importance of fluorescence in siiu hybridization (FISH) as an alternative molecular technique in the diagnosis of CMTlA.     

Inhibition of the Mixed Lymphocyte Culture Response by Antibody Following Successful Human Renal Transplantation

Immunoglobulin G, appearing after several months in the serum of a recipient of a successful kidney transplant from a closely matched sibling donor, was demonstrated to progressively inhibit unidirectional mixed lymphocyte cultures when donor lymphocytes were used either in responding or stimulating cell populations. The active recipient IgG had no effect in cultures in which donor cells were not used, nor did IgG obtained from other individuals show nonspecific inhibitory effects on cultures containing donor cells. It is suggested that the MLC inhibitory immunoglobulin may serve an immunoregulatory function after renal transplantation.     

A multi-modal treatment program for childhood trauma recovery:Women Recovering from Abuse Program (WRAP).

This article describes the Women Recovering from Abuse Program (WRAP), an outpatient day-hospital program for women suffering from the sequelae of childhood abuse. WRAP was conceived in 1998 by clinicians who advocated for its development based on a growing need to provide women who had experienced childhood trauma an alternative to an inpatient program. WRAP draws from a Stage 1 treatment approach to address chronic interpersonal trauma and dissociation by incorporating psychopharmacology, individual and group psychotherapy. The program is structured into two phases: a preparatory Building Resources Group (BRG) and an intensive multimodal segment comprised of seven types of group therapy. Each group is described in terms of the treatment rationale and its structure and process. Two research studies to date support the effectiveness of WRAP.     

Folic acid and vitamin B12 levels in pregnancy and their relation to megaloblastic anaemia

There is a significant fall in the serum folic acid level during pregnancy, reaching its lowest level at term. This is most pronounced in twin pregnancies. A similar but less spectacular fall occurs in the vitamin B₁₂ concentration.     

Neuroimaging of NREM sleep in primary insomnia: a Tc-99-HMPAO single photon emission computed tomography study

STUDY OBJECTIVES: The objectives of this study were to: 1) demonstrate the feasibility of combining polysomnography and SPECT neuroimaging to study NREM sleep in primary insomnia and 2) evaluate possible functional CNS abnormalities associated with insomnia. DESIGN: Patients with insomnia and good sleeper controls were studied polysomnographically for three nights with a whole brain SPECT Scan of NREM sleep on Night 3. Groups were screened for medical/psychiatric history, substance use, and matched on age, body mass index, and education. SETTING: Sleep Research Laboratory and Nuclear Medicine Center PARTICIPANTS: Nine females, 5 patients with chronic psychophysiologic insomnia and 4 healthy good sleepers (mean age 36 years, SD 12, range 27-55). INTERVENTIONS: N/A MEASUREMENTS AND RESULTS: Tomographs of regional cerebral blood flow during the 1st NREM sleep cycle were successfully obtained. Contrary to our expectations, patients with insomnia showed a consistent pattern of hypoperfusion across all 8 pre-selected regions of interest, with particular deactivation in the basal ganglia (p=.006). The frontal medial, occipital, and parietal cortices also showed significant decreases in blood flow compared to good sleepers (p<.05). Subjects with insomnia had decreased activity in the basal ganglia relative to the frontal lateral cortex, frontal medial cortex, thalamus, occipital and parietal cortices (p<.05). CONCLUSIONS: This study demonstrated the feasibility of combining neuroimaging and polysomnography to study cerebral activity in chronic insomnia. These preliminary results suggest that primary insomnia may be associated with abnormal central nervous system activity during NREM sleep that is particularly linked to basal ganglia dysfunction.     

Mutations in the human melanocortin-4 receptor gene associated with severe familial obesity disrupts receptor function through multiple molecular mechanisms

Mutations in the melanocortin-4 receptor gene (MC4R) represent the commonest monogenic cause of human obesity. However, information regarding the precise effects of such mutations on receptor function is very limited. We examined the functional properties of 12 different mutations in human MC4R that result in severe, familial, early-onset obesity. Of the nine missense mutants studied, four were completely unable to generate cAMP in response to ligand and five were partially impaired. Four showed evidence of impaired cell surface expression and six of reduced binding affinity for ligand. One mutation in the C-terminal tail, I316S, showed reduced affinity for alpha-MSH but retained normal affinity for the antagonist AgRP. None of the mutations inhibited signaling through co-transfected wild-type receptors. Thus, in the most comprehensive study to date of the functional properties of naturally occurring MC4R mutations we have (1) established that defective expression on the cell surface is a common mechanism impairing receptor function, (2) identified mutations which specifically affect ligand binding affinity thus aiding the definition of receptor structure-function relationships, (3) provided evidence against the notion that these receptor mutants act as dominant-negatives, and (4) identified a potentially novel molecular mechanism of receptor dysfunction whereby a mutation alters the relative affinities of a receptor for its natural agonist versus antagonist.     

Review of tethered cord syndrome with a radiological and anatomical study: Case report

Summary The primary tethered cord syndrome has been documented mainly in children and adolescents but also in adults, and patients may present with backache, neuromuscular skeletal changes such as club-foot, scoliosis, muscular atrophy, disturbances of gait, or dysfunction of bladder and rectum, or a combination of these conditions. The cadaveric case presented describes plain film radiographic and anatomical findings of spina bifida occulta at the first and second sacral levels, and an enlarged spinous process of the fifth lumbar vertebra, in a 78 year old male cadaver with a tethered spinal cord terminating at the first sacral level. During life, this man had not undergone surgery for tethered spinal cord.

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Revue du syndrome de moelle attachée: étude radiologique et anatomique à propos d'un cas

Résumé Le syndrome de moelle attachée primaire a souvent été décrit chez l'enfant et l'adolescent mais aussi chez l'adulte, les patients pouvant se présenter avec des douleurs du dos, des modifications neuro-musculaires et squelettiques comme un pied bot, une scoliose, une atrophie musculaire, des anomalies de la marche, des dysfonctionnements de la vessie et/ou du rectum, ou une combinaison de ces différents symptômes. L'observation rapportée ici est l'étude anatomique et radiologique d'un spina bifida oculta des première et deuxième vertèbres sacrées associé à l'élargissement du processus épineux de la cinquième vertèbre lombaire chez un cadavre mâle de 78 ans ayant une moelle épinière attachée au niveau de la première vertèbre sacrée. Durant sa vie ce patient n'avait pas subi de chirurgie pour cette moelle attachée.