A family with Parkinsonism, essential tremor, restless legs syndrome, and depression.

BACKGROUND: Previous epidemiologic and genetic studies have suggested a link between Parkinson disease (PD), essential tremor (ET), and restless legs syndrome (RLS). METHODS: We describe the clinical, PET, and pathologic characteristics of an extensive kindred from Arkansas with hereditary PD, ET, and RLS. The pedigree contains 138 individuals. Sixty-five family members were examined neurologically up to 3 times from 2004 to 2010. Clinical data were collected from medical records and questionnaires. Genetic studies were performed. Five family members underwent multitracer PET. Two individuals with PD were examined postmortem. RESULTS: Eleven family members had PD with generally mild and slowly progressive symptoms. Age at onset was between 39 and 74 years (mean 59.1, SD 13.4). All individuals treated with l-dopa responded positively. Postural or action tremor was present in 6 individuals with PD, and in 19 additional family members. Fifteen persons reported symptoms of RLS. PET showed reduced presynaptic dopamine function typical of sporadic PD in a patient with PD and ET, but not in persons with ET or RLS. The inheritance pattern was autosomal dominant for PD and RLS. No known pathogenic mutation in PD-related genes was found. Fourteen of the family members with PD, ET, or RLS had depression. Neuropathologic examination revealed pallidonigral pigment spheroid degeneration with ubiquitin-positive axonal spheroids, TDP43-positive pathology in the basal ganglia, hippocampus, and brainstem, and only sparse Lewy bodies. CONCLUSION: Familial forms of PD, ET, RLS, and depression occur in this family. The genetic cause remains to be elucidated.

Proteomic data in meningiomas: post-proteomic analysis can reveal novel pathophysiological pathways.

Meningiomas account for approximately 20% of adult primary intracranial tumours. WHO I meningiomas are the most common and are generally benign, but can progress, recur or transform to WHO II or WHO III grades over many years. A systematic review of multiple independent shotgun proteomic analyses of meningioma was performed to provide insight into underlying disease pathways. Shotgun proteomics has been conducted in seven meningioma related studies but there is considerable variation in aims, methodology, statistical power and the use of control tissue between these studies. Fifteen proteins which are different between WHO I and WHO II meningiomas and nine proteins which are different between WHO II and WHO III meningiomas have been described but without a view of their biological significance. Network analysis of proteins different between WHO I and WHO II meningiomas provided a coherent hypothesis for the involvement of these proteins in meningioma. Western blot analyses of meningioma tissue provided a measure of support for a core component in the network (involving VDAC2, APOA1 and HNF4α) but highlighted intrinsic difficulty of proteomic and biochemical analysis of meningiomas (as a consequence of gross alterations in tissue composition). Systematic review of shotgun proteomics and network analysis provides insight into meningioma pathophysiology despite the many barriers and difficulties that are inherent to this type of study.

Inter- and intraspecific comparisons of antiherbivore defenses in three species of rainforest understory shrubs.

Plants defend themselves against herbivores and pathogens with a suite of morphological, phenological, biochemical, and biotic defenses, each of which is presumably costly. The best studied are allocation costs that involve trade-offs in investment of resources to defense versus other plant functions. Decreases in growth or reproductive effort are the costs most often associated with antiherbivore defenses, but trade-offs among different defenses may also occur within a single plant species. We examined trade-offs among defenses in closely related tropical rain forest shrubs (Piper cenocladum, P. imperiale, and P. melanocladum) that possess different combinations of three types of defense: ant mutualists, secondary compounds, and leaf toughness. We also examined the effectiveness of different defenses and suites of defenses against the most abundant generalist and specialist Piper herbivores. For all species examined, leaf toughness was the most effective defense, with the toughest species, P. melanocladum, receiving the lowest incidence of total herbivory, and the least tough species, P. imperiale, receiving the highest incidence. Although variation in toughness within each species was substantial, there were no intraspecific relationships between toughness and herbivory. In other Piper studies, chemical and biotic defenses had strong intraspecific negative correlations with herbivory. A wide variety of defensive mechanisms was quantified in the three Piper species studied, ranging from low concentrations of chemical defenses in P. imperiale to a complex suite of defenses in P. cenocladum that includes ant mutualists, secondary metabolites, and moderate toughness. Ecological costs were evident for the array of defensive mechanisms within these Piper species, and the differences in defensive strategies among species may represent evolutionary trade-offs between costly defenses.

Clinical and genetic evaluation of 8 Polish families with levodopa-responsive parkinsonism.

We studied 8 large Polish families with parkinsonism, 6 of which were newly identified. Thirty-six family members had well-documented levodopa-responsive parkinsonism. The phenotype of affected individuals was indistinguishable from that of persons with idiopathic Parkinson disease (PD). The pattern of inheritance in 5 families was consistent with autosomal dominant transmission; in 3 families the mode of inheritance was uncertain. Single photon emission computed tomography (SPECT) studies with the dopamine transporter radioligand [(123)I]FP-CIT were performed in 1 family. The SPECT study showed striatal presynaptic dopaminergic degeneration consistent with sporadic PD in 1 affected family member and no signs of nigrostriatal dopaminergic dysfunction in 5 at-risk individuals. Sequence analysis in all 8 families excluded known genes associated with familial parkinsonism. Genome-wide 2-point linkage studies in the largest 2 families did not identify significant linkage (z > 3.0), although positive scores were obtained for 5q23 (D5S1462 and D5S2501), a locus previously implicated in disease susceptibility.

Aging and lineup performance at long retention intervals: effects of metamemory and context reinstatement.

Young (18-30 years) and older (62-79 years) adults (N = 96) engaged in a 20-min live interaction with the future target in a lineup task. One month later, participants were interviewed about the events in the prior encounter (with or without context reinstatement), and then they saw a target-present (TP) or target-absent (TA) lineup. The lineup was followed by the Benton Face Recognition Test (A. Benton, A. Sivan, K. Hamsher, N. Varney, & O. Spreen, 1994), which correlated positively with accuracy in TP, especially for young adults. False identification in TA was associated with (a) higher scores on a memory self-efficacy scale and (b) higher recall of information about the initial event, although only for seniors. Results suggested that age-related increases in false identification generalize to ecologically valid conditions and that seniors' performance on lineups is negatively related to verbal recall as well as to self-reports of satisfactory experiences with memory in life.

Cenocladamide, a dihydropyridone alkaloid from Piper cenocladum.

A dihydropyridone alkaloid, cenocladamide, and a derivative of piplartine, 4'-desmethylpiplartine were isolated along with piplartine from the leaves of Piper cenocladum. The structures of the new compounds were determined by spectroscopic methods and by comparison to piplartine. Concentrations of these amides in plants with and without ant mutualists, are compared.

Age differences in accuracy and choosing in eyewitness identification and face recognition.

Studies of aging and face recognition show age-related increases in false recognitions of new faces. To explore implications of this false alarm effect, we had young and senior adults perform (1) three eye-witness identification tasks, using both target present and target absent lineups, and (2) and old/new recognition task in which a study list of faces was followed by a test including old and new faces, along with conjunctions of old faces. Compared with the young, seniors had lower accuracy and higher choosing rates on the lineups, and they also falsely recognized more new faces on the recognition test. However, after screening for perceptual processing deficits, there was no age difference in false recognition of conjunctions, or in discriminating old faces from conjunctions. We conclude that the false alarm effect generalizes to lineup identification, but does not extend to conjunction faces. The findings are consistent with age-related deficits in recollection of context and relative age invariance in perceptual integrative processes underlying the experience of familiarity.

Inversion and processing of component and spatial-relational information in faces.

This study compared effects of inversion on perceptual processing of faces with distorted components (eyes and mouths) and faces distorted by altering spatial relations between components. In a rating task, participants inversion reduced the rated grotesqueness of spatially distorted faces but not that of faces with altered components. In a comparison task, pairs of faces were shown side by side; participants judged whether they were identical or different. Inversion greatly reduced the rate at which participants responded within 3 s to pairs that differed spatially, but not pairs that differed componentially. Also, latencies for detecting spatial differences were lengthened by inversion more than latencies for detecting componential differences. Results support the hypothesis that inversion impairs encoding of spatial-relational information more than, or instead of, componential information, depending on the task.

Neurobehavioural consequences of closed head injury in older adults.

This study examined the neurobehavioural effects of closed head injury (CHI) in adults aged 50 years and older. Twenty two mild to moderate CHI patients who were within seven months of the injury were administered measures of language, memory, attention, and executive functioning. Compared with demographically similar normal controls, the patients exhibited significantly poorer functioning on the cognitive domains. Naming and word fluency under timed conditions, verbal and visual memory, and the ability to infer similarities were especially vulnerable. These initial findings indicate that CHI in older adults produces considerable cognitive deficits in the early stages of recovery. Future research should characterise long term outcome and the potential links between head injury and the development of progressive dementia.

Inversion and configuration of faces.

If the mouth and eyes of a face are inverted, the altered construction appears grotesque when upright, but not when upside-down. Three studies of this "Thatcher illusion" employed faces that were grotesque when upright because: (a) their eyes and mouths had been inverted ("Thatcherized" faces), (b) their eyes and mouths had been moved (spatially distorted faces), or (c) they had grotesque posed expressions. Inversion reduced the apparent grotesqueness of both Thatcherized and spatially distorted faces, but not grotesque-expression faces. Moreover, Thatcherized and distorted faces, although not grotesque-expression faces, were judged as more similar to normal, smiling faces when face-pairs were inverted than when they were upright. Similarity ratings to inverted face-pairs were correlated with latencies of response to these pairs in a task that encouraged attention to components (e.g., mouths, eyes) rather than wholistic properties. Similarity ratings to upright face-pairs showed no such correlation, and this and other findings suggested that although similarity ratings to upright faces are based on wholistic information, similarity ratings to inverted faces are based largely on components. The Thatcher illusion reflects a disruption of encoding of wholistic information when faces are inverted.

Bone mineral content in children 1 to 6 years of age. Detectable sex differences after 4 years of age.

Age- and sex-specific bone mineral measures have not been available for healthy preschool children. We determined bone mineral content (BMC) and bone width in 89 children 1 to 6 years of age using direct photon absorptiometry at the one-third distal radius site. The BMC increased significantly with age, and bone width increased slightly with age. After stratification by age, male and female children had similar BMC from 1 to 4 years of age, but female children had significantly lower BMC at 5 to 6 years of age.

Reflection-impulsivity and short-term memory in emotionally disturbed children.

In an investigation of the relationship between the reflection-impulsivity cognitive dimension and short-term memory in emotionally disturbed children, 42 Ss were administered the Matching Familiar Figures Test and the Visual-Aural Digit Span Test. Analysis of covariance indicated that on all memory tasks the reflective Ss were better than the impulsive subjects.

Mineral homeostasis during lactation- relationship to serum 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, parathyroid hormone and calcitonin.

During lactation maternal losses of calcium and phosphorus through human milk average 220 to 340 and 110 to 170 mg/day, respectively. The present study reports maternal serum concentrations of vitamin D metabolites, parathyroid hormone, calcitonin, calcium, magnesium, and phosphorus during the first 6 months of lactation. Serum calcium and magnesium concentrations increased during the first 6 months of lactation. Serum 1,25-(OH)2 vitamin D was increased at 6 months of lactation compared to values in nonpregnant nonlactating controls. During this same period, serum parathyroid hormone decreased slightly and serum calcitonin remained unchanged. Our data do not support the observation that lactation represents a state of physiological hyperparathyroidism. On the contrary, our results suggest that lactating women are able to adequately compensate for the losses of calcium and phosphorus during the early months of lactation, although increased serum 1,25-(OH)2 vitamin D concentrations may be necessary to maintain calcium homeostasis with lactation beyond 6 months.

Bone mineral content and serum 25-hydroxyvitamin D concentration in breast-fed infants with and without supplemental vitamin D.

Eighteen term, healthy, appropriate for gestational age, breast-fed infants were studied in a double-blind prospective study to determine whether or not supplemental vitamin D affected bone mineralization. All patients were from a single, private pediatric practice. Nine infants were randomly assigned to a vitamin D supplement of 400 IU/day and nine infants to a placebo. By 12 weeks of age, infants receiving placebo had a significant decrease in bone mineralization and in serum 25-hydroxyvitamin D concentrations compared to the vitamin D-supplemented group. It is not known whether or not the increased BMC at 12 weeks of age in vitamin D-supplemented breast-fed infants is of ultimate value. Supplemental vitamin D may be necessary for optimal bone mineralization in term breast-fed infants. A longer follow-up study and additional analyses are required to make conclusive statements.

Physiologic cholestasis: elevation of the primary serum bile acid concentrations in normal infants.

Immaturity of hepatic excretory function resulting in a period of "physiologic cholestasis" may occur during early life. Serum bile acids should accurately reflect maturation of the enterohepatic circulation; we therefore determined serum concentrations of the primary bile acids in normal infants to define age-related changes. There was a striking rise in serum cholylglycine and conjugates of chenodeoxycholate during the first few days of life over levels detected in cord sera; the values attained were significantly greater than maximal postprandial concentrations found in children over 1 yr of age (p less than 0.01). There was a gradual decline in bile acid concentration; however cholylglycine remained higher than the postprandial values of older children until 4 mo and chenodeoxycholate until 6 mo of age. In 12 infants a liquid feeding stimulated a greater maximal postprandial cholylglycine concentration and integrated area under the meal curve than that achieved in children (p less than 0.01). There was no difference in the postprandial response in chenodeoxycholate in these infants compared with the older subjects. We conclude that serum bile acids are elevated in normal infants and that the subsequent decline to levels of the child and adult demonstrates the evolving maturation of liver function during infancy.

Biosynthesis of ochratoxin A.

Biosynthesis of ochratoxin A by Aspergillus ochraceus Wilh. was investigated by radiolabeling experiments in which phenylalanine-1-(14)C and sodium acetate-2-(14)C were supplied to the fungus in sucrose-yeast extract medium. Results showed that phenylalanine was incorporated unaltered into the phenylalanine moiety of ochratoxin A, whereas the isocoumarin moiety of ochratoxin A was mostly derived via acetate condensation.