Looking for the active hydrogen species in a 5 wt% Pt/C catalyst: a challenge for inelastic neutron scattering.

We looked for the active hydrogen species in a highly dispersed and very homogeneous 5 wt% Pt/C industrial catalyst (Pt particle mean diameter of 2.0 ± 0.5 nm) for hydrogenation reactions, by coupling H2 adsorption measurements with Inelastic Neutron Scattering (INS). Taking advantage of the enormous progress undergone by INS instruments, we succeeded in collecting INS spectra of unprecedented quality that allowed us to: (1) demonstrate that the Pt nanoparticles are mainly located at the regular edges of the sp2 graphitic domains on the activated carbon; (2) validate that most of the H2 physisorbed on the carbon is side-on adsorbed; (3) detect for the first time H2 molecules adsorbed on hydride-covered Pt nanoparticles; (4) observe Pt-hydrides (on the Pt/C catalyst with the lowest Pt loading among those investigated by INS so far) and (5) provide evidence for the occurrence of spillover of atomic hydrogen from the Pt surface to unsaturated reactive sites located at the irregular borders of the sp2 domains on the activated carbon.

Left ventricular remodeling in patients with metabolic syndrome: influence of gender.

AIM: The study was aimed to evaluate the influence of gender on left ventricular (LV) remodeling in metabolic syndrome (MetS). METHODS AND RESULTS: We enrolled 200 subjects without diabetes or overt cardiovascular diseases, never treated with anti-hypertensive drugs or statins: 60 men and 40 women with MetS matched by age, gender and 24 h systolic and diastolic blood pressure (BP) with 60 men and 40 women without MetS. The patients underwent blood tests, 24 h our BP monitoring, LV echocardiographic examination. LV mass indexed by eight(2.7) was significantly greater in men and women with MetS than without MetS. Compared with women without MetS, women with MetS had significantly higher posterior wall thickness and relative wall thickness, greater prevalence of LV concentric remodeling/hypertrophy and lower indices of LV diastolic function, whereas all these parameters were not significantly different between men with and without MetS. MetS was an independent predictor of relative wall thickness and LV mass index in women, but not in men. CONCLUSION: The impact of MetS on LV remodeling is significantly influenced by gender: the effects of MetS are more pronounced in women, with development of LV concentric hypertrophy/remodeling and preclinical diastolic dysfunction.

Mapping of a gene for Parkinson's disease to chromosome 4q21-q23.

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting approximately 1 percent of the population over age 50. Recent studies have confirmed significant familial aggregation of PD and a large number of large multicase families have been documented. Genetic markers on chromosome 4q21-q23 were found to be linked to the PD phenotype in a large kindred with autosomal dominant PD, with a Zmax = 6.00 for marker D4S2380. This finding will facilitate identification of the gene and research on the pathogenesis of PD.

Mutation in the alpha-synuclein gene identified in families with Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent. A pattern of familial aggregation has been documented for the disorder, and it was recently reported that a PD susceptibility gene in a large Italian kindred is located on the long arm of human chromosome 4. A mutation was identified in the alpha-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype. This finding of a specific molecular alteration associated with PD will facilitate the detailed understanding of the pathophysiology of the disorder.

An unusual cause of traumatic reticulitis/reticuloperitonitis in a herd of Swiss dairy cows nearby an airport.

This report describes the findings in five cows from one dairy herd, in which all 31 cows were slaughtered or euthanised because of traumatic reticuloperitonitis. All the cows had numerous thin sharp pieces of metal attached to a magnet in the reticulum, giving the magnet a hedgehog-like appearance. Investigation revealed that the cattle had eaten forage harvested from a field immediately adjacent to an airport. The snow was cleared from the airport runways with a machine that had a wire-bristle brush attachment. Mechanical wear resulted in numerous wire bristles breaking and these were blown with the snow onto the field in question. The wire then became accidentally incorporated into the hay and grass silage at harvest the next summer and was ingested by the cattle in the fall and winter. To prevent further cases, approximately 200 tonnes of hay and grass silage contaminated with wire were discarded and 30 hectares of the 50-hectare field were cultivated and re-sown. The wire-bristles of the snow plow were replaced with plastic bristles. The cost of this and the livestock loss was several hundred thousand Swiss Francs.

Variable expressivity in familial restless legs syndrome.

A 62-year-old man with a 20-year history of excessive daytime somnolence and kicking during sleep was an obligate carrier of the restless legs syndrome gene because his paternal grandfather, father, and all three of his children had symptoms of restless legs syndrome. The patient himself, however, denied motor restlessness after a careful and exhaustive medical history and he was originally believed to have periodic movements in sleep without restless legs. Close clinical observation did reveal nighttime motor restlessness, although the patient continued to deny its importance. Polysomnography showed frequent periodic movements in sleep. We conclude that there can be variable expressivity of the clinical features in familial restless legs syndrome and that there are probably some relatively nonrestless patients with prominent periodic movements in sleep who are carriers of the restless legs syndrome gene. Some sleep-disordered patients who are believed to have only periodic movements in sleep may have a forme fruste of autosomal dominant restless legs syndrome. If one does not examine these patients carefully at night and take an adequate family history, one may miss the diagnosis of restless legs syndrome.

A 17th-century founder gives rise to a large north American pedigree of autosomal dominant spinocerebellar ataxia not linked to the SCA1 locus on chromosome 6.

There have been three reports since 1969 of members of a "W" family with autosomal dominant spinocerebellar ataxia (SCA), and various conclusions have been drawn about the nosology. This pedigree has been traced back over 300 years through 11 generations. Although phenotypically similar to the disorder in the Schut-Swier, Nino, and other kindreds, the disorder in the W family is not linked to the SCA1 locus on chromosome 6, as reported in those hereditary ataxia pedigrees. The W family represents the largest such North American kindred yet reported. We examined 33 family members of a distantly related branch of the W family, determined the cumulative age of onset, and projected the number of present-day gene carriers. Two cases illustrate the spectrum of symptoms among family members. Age of onset and presenting symptom, however, seem to correlate both in our patients and in those previously reported. Between 2,000 and 5,000 individuals are estimated to be at risk of developing the disorder within this pedigree alone. The pedigree reported here will be valuable in the identification and cloning of a gene for hereditary ataxia, designated "SCA2" at the Eleventh International Workshop on Human Gene Mapping.

Pelizaeus-Merzbacher-like disease: exclusion of the proteolipid protein locus and documentation of a new locus on Xq.

A large X-linked kindred with Pelizaeus-Merzbacher like disease (Pelizaeus-Merzbacher disease [PMD] lacking a proteolipid protein [PLP] mutation) was studied for linkage to 34 X-chromosome short tandem repeat polymorphism markers. Recombinational events excluded linkage to PLP and supported linkage to a 9.4-cM critical region more than 10 cM away from PLP on the X chromosome. A maximum 2-point lod score of 3.91 was observed for DXS441 at theta = 0.0. Neuropathologic study of one affected male showed intact myelin. The data thus support a different etiology for a disease that clinically resembles PMD, distinguishable phenotypically only by degree of myelin involvement. Other patients with the clinical diagnosis of PMD but without PLP mutations could have mutations at this new locus.

A clinical genetic study of Parkinson's disease: evidence for dominant transmission.

We used a family history questionnaire, semi-structured interview, and personal examination of secondary cases to collect data on the prevalence of Parkinson's disease (PD) in relatives of patients seen consecutively for 1 year and assessed the proportion of secondary cases of PD as a function of pedigree completeness. Survival analysis methods were applied to estimate the lifetime risk and age-at-onset distribution of PD among first-degree relatives of probands. When we considered siblings of probands with affected parents, the cumulative risk increased significantly over siblings of probands without affected parents, suggesting significant familial aggregation in a subset of randomly ascertained families. We further analyzed 80 multicase families with two or more affected individuals. Age-adjusted segregation ratios approaching 0.5 and similar proportions of affected parents and siblings, as well as the distribution of ancestral secondary cases, were compatible with an autosomal dominant mode of inheritance with reduced penetrance in a subset of PD.

Autosomal dominant parkinsonism with benign course and typical Lewy-body pathology.

The few previously reported patients with familial parkinsonism and Lewy-body pathology in the substantia nigra displayed a variety of clinical and pathologic syndromes. We now describe a family with very slowly progressive Parkinson's disease (PD) that has, in most cases, responded poorly to levodopa and includes subjective visual difficult. Four personally confirmed cases--with onset at ages 35, 25, 16, and 16-have occurred in three generations, and four suspicious cases have occurred in three other generations. There has been a trend toward progressively younger age of onset. One autopsied case showed a distribution of cell loss and Lewy bodies typical of PD. The hereditary pattern is most compatible with autosomal dominance. This kindred's illness shows that a presumably single Mendelian dominant gene can cause the clinical and pathologic features of PD, and further extends the clinical spectrum of pathologically typical Lewy-body PD.

Gerstmann-Sträussler-Scheinker disease with mutation at codon 102 and methionine at codon 129 of PRNP in previously unreported patients.

We present two patients with Gerstmann-Sträussler-Scheinker disease (GSS), one from a previously undescribed kindred and one from the Canadian branch of a previously reported British kindred. In both patients, GSS is caused by a substitution of thymine for cytosine at codon 102 of the prion protein gene (PRNP). In each patient, we confirmed the clinical diagnosis by neuropathologic examination. The mutation, causing a substitution of leucine for proline at residue 102 (P102L) of the prion protein, has been previously reported in at least 30 other families. In the patients described here, the mutation was in coupling with methionine at PRNP codon 129.

Epidemiologic study of 203 sibling pairs with Parkinson's disease: the GenePD study.

OBJECTIVE: To examine patterns of familial aggregation and factors influencing onset age in a sample of siblings with PD. METHODS: Sibling pairs (n = 203) with PD were collected as part of the GenePD study. Standardized family history, medical history, and risk factor data were collected and analyzed. RESULTS: The mean age at onset was 61.4 years and did not differ according to sex, exposure to coffee, alcohol, or pesticides. Head trauma was associated with younger onset (p = 0.03) and multivitamin use with later onset (p = 0.007). Age at onset correlation between sibling pairs was significant (r = 0.56, p = 0.001) and was larger than the correlation in year of onset (r = 0.29). The mean difference in onset age between siblings was 8.7 years (range, 0 to 30 years). Female sex was associated with increased frequency of relatives with PD. The frequency of affected parents (7.0%) and siblings (5.1%) was increased when compared with frequency in spouses (2.0%). CONCLUSIONS: The greater similarity for age at onset than for year of onset in sibling pairs with PD, together with increased risk for biological relatives over spouses of cases, supports a genetic component for PD. Risk to siblings in this series is increased over that seen in random series of PD cases; however, patients in this sample have similar ages at onset and sex distribution as seen for PD generally. These analyses suggest that factors influencing penetrance are critical to the understanding of this disease.

Genome-wide scan for Parkinson's disease: the GenePD Study.

A genome-wide scan for idiopathic PD in a sample of 113 PD-affected sibling pairs is reported. Suggestive evidence for linkage was found for chromosomes 1 (214 cM, lod = 1.20), 9 (136 cM, lod = 1.30), 10 (88 cM, lod = 1.07), and 16 (114 cM, lod = 0.93). The chromosome 9 region overlaps the genes for dopamine beta-hydroxylase and torsion dystonia. Although no strong evidence for linkage was found for any locus, these results may be of value in comparison with similar studies by others.

Altered red cell osmotic fragility in Huntington disease (HD).

We have studied in fresh and 24-hour incubated samples the osmotic fragility of erythrocytes from 13 individuals with Huntington disease (HD) and 22 at-risk, asymptomatic individuals. Five older at-risk, asymptomatic individuals and six Alzheimer disease individuals were also studied. Results suggest that osmotic fragility of red cells from HD individuals in significantly decreased in fresh (P less than 0.0001) and incubated (P less than 0.0001) samples. At-risk individuals appear to fall into two groups: 1) those with normal osmotic fragility (n =10), and 2) those with decreased osmotic fragility (n = 12). Fragility in older at-risk persons and those with Alzheimer disease were within normal limits. These data suggest that red cell osmotic fragility measurement may be useful to identify at-risk persons with an HD gene; however, longitudinal follow-up will be required to confirm the predictive power of this observation. These data suggest additional support for focusing on the erythrocyte in investigating the molecular pathogenesis of HD.

Attitudes regarding utilization of artificial insemination by donor in Huntington disease.

We report on a study of attitudes toward artificial insemination by donor (AID) of persons at risk for Huntington disease (HD). The subjects of the study were 91 at risk persons and 68 matched controls. Both groups were divided by sex and age (45 yr less than or equal to vs greater than or equal to 46 yr). Demographic data included age, occupation, marital status, religion, education, ethnic background, and family size. We recorded 1) attitudes toward reproduction, 2) nature of contact with affected family member(s), 3) effects of HD on family planning, 4) attitudes toward AID, and 5) concern about donor selection criteria. Results suggest that 1) men and women differ in several ways with regard to their views about AID, and 2) that more vigorous educational programs might increase utilization of AID for the prevention of not only HD, but other human genetic diseases as well.

A genetic study of red cell osmotic fragility in Huntington's disease.

The erythrocyte osmotic fragility was evaluated on 19 unmedicated subjects with Huntington's disease and 42 individuals at 50% risk, 27 children at 25% risk, and a group of 60 hematologically normal control persons. Five older subjects at 50% risk for Huntington's disease as well as 6 Alzheimer's disease individuals were also evaluated for comparison. The osmotic fragility of fresh and 24-hour incubated red cells was analyzed and a fragility index calculated for each individual. The fragility index for the Huntington's disease group was statistically lower than that of the control group (P less than .001) suggesting that the Huntington's disease erythrocytes had a reduced osmotic fragility. In the 50% risk group, 45% of the subjects demonstrated decreased osmotic fragility and 55% had normal fragility. For those subjects in the 25% risk group, 22.2% had decreased fragility and 77.8% had normal fragility. Twenty-seven offspring were evaluated of the 14 persons at 50% risk for Huntington's disease with children; eight of the 14 individuals at 50% risk showed normal fragility and all 16 of their children showed fragility indices with the normal range. The remaining six persons at 50% risk for Huntington's disease had increased erythrocyte fragility and out of their 11 children, five showed normal fragility and six had decreased fragility. These data support the hypothesis of reduced erythrocyte osmotic fragility in individuals affected with and at risk for Huntington disease, and demonstrate the need of further study of the erythrocyte in this complex behavioral genetic disease.

Reduced fecundity in male ALS gene-carriers.

In order to study genetic aspects in multicase families, 89 amyotrophic lateral sclerosis (ALS) and 214 Parkinson disease (PD) kindreds were analyzed in parallel studies. Obligate gene-carriers were identified as described previously [Chatkupt et al., 1992: Am J Med Genet 44:508-512]. There were fewer children per gene-carrier male (2.42) than per gene-carrier female (3.25, Student's t-test, P < .0003) for ALS but not for other diseases. The data taken together suggest that fecundity in ALS gene-carriers was reduced in males, possibly as a result of reduced fertility. Since childbearing is usually accomplished well before the onset of neurological symptoms in ALS, and since reduced fecundity was found in male ALS gene-carriers, these findings raise the possibility that an ALS gene might have a pleiotrophic effect on fertility in males occurring decades before the onset of neurological symptoms. Evidence is presented linking reactive oxygen species to reduced fertility in males. Alternatively, decreased or nonfunctional androgen receptors could play a role.

Short tandem repeat polymorphism linkage studies in a new family with X-linked mental retardation (MRX20).

A family with X-linked recessive mental retardation (XLMR) without other obvious manifestations (MRX20) was studied with 14 short tandem repeat polymorphism (STRP) markers. Two-point lod scores above 3 were obtained with DXS1003, DXYS1, DXS3, and DXS458. A multipoint lod score of 4.25 was obtained with peak at DXS1003. Recombination events identify a 55.6 cM interval between DXS1068 and DXS454, while a one unit support interval identifies 40 cM between MAOA and DXS458.

Segregation analysis of Parkinson disease revealing evidence for a major causative gene.

The role of genetics in Parkinson disease (PD) continues to be an area of considerable interest and controversy. We collected information involving the nuclear families of 948 consecutively ascertained PD index cases from the University of Virginia (UVA) Health System, the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson (RWJ) School of Medicine, and Boston University (BU) School of Medicine. We performed a segregation analysis to assess evidence for the presence of a Mendelian pattern of familial transmission. The proportion of male (60.4%) and female (39.6%) cases, the mean age of onset (57.7 years), and the proportion of affected fathers (4.7%), mothers (6.6%), brothers (2.9%), and sisters (3.2%) were similar across the three sites. While most of the index cases were male, modestly more of the reported affected relatives were female. These analyses support the presence of a rare major Mendelian gene for PD in both the age-of-onset and susceptibility model. The age-of-onset model provides evidence for a gene that influences age-dependent penetrance of PD, influencing age of onset rather than susceptibility. We also found evidence for a Mendelian gene influencing susceptibility to the disease. It is not evident whether these two analyses are modeling the same gene or different genes with different effects on PD. The finding of significant genes influencing penetrance for PD raises the question of whether these may interact with environmental factors or other genes to increase the risk for PD. Such gene environment interactions, involving reduced penetrance in PD, may explain the low concordance rates among monozygotic twins for this disease.

Effects of chromium(VI) and chromium(III) on energy charge and oxygen consumption in rat thymocytes.

The cytotoxic effects of chromium compounds in two oxidation states have been studied in rat thymocytes. endogenous nucleotide levels and oxygen consumption were examined as relevant parameters of the physiological state of the cell. Incubation of rat thymocytes with Cr(VI) produced a marked unbalance of endogenous purine nucleotide pool and a parallel decrease in oxygen consumption. A close correlation between the reduction of oxygen consumption and ATP level in rat thymocytes treated with increasing concentrations of Cr(VI) has been found. In rat thymocytes permeabilized with digitonin and in isolated rat liver mitochondria both Cr(VI) and Cr(III) showed, at different range of concentrations, a marked inhibition of maximal oxygen consumption rate (uncoupled respiration). The effects observed were depending on chromium oxidation state and on different mitochondrial sites of substrate oxidation.