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To elucidate the differences among dementia with Lewy bodies (DLB), Parkinson disease with dementia (PDD), and Parkinson disease without dementia (PD), with respect to the involvement of the autonomic nervous system, we clinically investigated the cutaneous and cardiovascular autonomic functions in patients with Lewy body disease.

To characterize brain cholinergic deficits in Parkinson disease (PD), PD with dementia (PDD), and dementia with Lewy bodies (DLB).

The Rap-pathway has been implicated in various cellular processes but its exact physiological function remains poorly defined. Here we show that the Caenorhabditis eleganshomologue of the mammalian guanine nucleotide exchange factors PDZ-GEFs, PXF-1, specifically activates Rap1 and Rap2. Green fluorescent protein (GFP) reporter constructs demonstrate that sites of pxf-1expression include the hypodermis and gut. Particularly striking is the oscillating expression of pxf-1in the pharynx during the four larval molts. Deletion of the catalytic domain from pxf-1leads to hypodermal defects, resulting in lethality. The cuticle secreted by pxf-1mutants is disorganized and can often not be shed during molting. At later stages, hypodermal degeneration is seen and animals that reach adulthood frequently die with a burst vulva phenotype. Importantly, disruption of rap-1leads to a similar, but less severe phenotype, which is enhanced by the simultaneous removal of rap-2.In addition, the lethal phenotype of pxf-1can be rescued by expression of an activated version of rap-1.Together these results demonstrate that the pxf-1/rappathway in C. elegansis required for maintenance of epithelial integrity, in which it probably functions in polarized secretion.

The authors performed linkage analysis in 39 families with autosomal recessive early-onset PD (AR-EOPD) negative for parkinand DJ-1mutations. Eight families including three Japanese, two Taiwanese, one Turkish, one Israeli, and one Philippine showed evidence of linkage with PARK6 with multipoint log of the odds (lod) score of 9.88 at D1S2732. The results indicate worldwide distribution of PARK6-linked parkinsonism.

An ingot of high-purity 70 mass% Cr–Fe alloy was prepared by high-frequency induction melting in a high-purity argon atmosphere using a cold copper crucible. Its tensile properties such as hot-ductility and tensile strength were measured, and compared with the results for a high-purity 50 mass% Cr–Fe alloy, a high-purity 60 mass% Cr–Fe alloy and a Ni-based super-alloy. The formation of σ-phase was also examined. The purity of a 70Cr–Fe alloy (70 mass% Cr–Fe alloy) ingot is more than 99.98 mass% and the total amount of gaseous impurities (C, N, O, S, H) in the 70Cr–Fe alloy is 69.9 mass ppm. The strength of the 70Cr–Fe alloy is higher than those of the 60Cr–Fe alloy and the 50Cr–Fe alloy at the temperatures between 293 and 1573 K, without decrease in ductility with increasing Cr content. The 70Cr–Fe alloy also possesses excellent high-temperature ductility. The σ-phase was not observed after aging of 3.6 Ms at 873 K. Consequently, the 70Cr–Fe alloy is an excellent alloy as the base of super heat-resistant alloys.

Tensile properties of high-purity Fe–50Cr and Fe–50Cr–8W alloys irradiated by neutrons have been investigated. The behavior of precipitate formation on dislocation loops in high-purity Fe–(9–70)Cr alloys has been examined during 1 MeV electron irradiation in a high voltage electron microscope. The neutron irradiation was performed at 673, 773 and 873 K in the Modified Japan Research Reactor-3 (JRR-3M) to about 0.4 dpa. In the Fe–50Cr and Fe–50Cr–8W alloys irradiated at 673 K, no elongation was observed in the test performed at 673 K. The elongations were observed to recover in the tensile test at 873 K. They also recovered largely after a heat treatment at 873 K for 10 h. However, heat treatment at 873 K for 10 h hardly improved the ductility for the Fe–50Cr alloy irradiated at 873 K. The defect clusters formed at 873 K by the irradiation were relatively stable. Moiré fringe contrast due to the precipitate formation on dislocation loops was observed in the Fe–(9–70)Cr alloys irradiated by electrons at temperatures lower than about 773 K. The precipitates were identified as α'-phase in the Fe–(9–30)Cr alloys, but as α-phase in the Fe–70Cr alloy. The loops formed in Fe–(9–70)Cr alloys were of two types: either on {100} planes with Burgers vector b = a〈100〉 or on {111} planes with b = (a/2)〈111〉. Their number density decreased with irradiation temperature.

The modified pullulan derivatives having N-phenylurethane and N-hexylurethane groups in the side-chain (PI-PL and HI-PL) have been synthesized by the reactions of pullulan with phenyl isocyanate (PIC) and hexyl isocyanate (HIC), respectively. The structure of the derivatives was characterized by gel permeation chromatography, IR and 1H NMR spectroscopy. From the measurement of differential scanning calorimetry of PI-PL and HI-PL with various degrees of addition (DA) in the range of 0–3, it was revealed that both the derivatives showed a clear glass transition temperature (Tg), which decreased with the increasing DA of PIC and HIC. The pullulan derivatives were water-resistant and had good solubility in general organic solvents.

Objectives Urinary dysfunction and orthostatic hypotension are the prominent autonomic features in multiple system atrophy (MSA). A detailed questionnaire was given and autonomic function tests were performed in 121 patients with MSA concerning both urinary and cardiovascular systems. Methods Replies to the questionnaire on autonomic symptoms were obtained from 121 patients including three clinical variants; olivopontocerebellar atrophy (OPCA) type in 48, striatonigral degeneration (SND) type in 17, and Shy-Drager type in 56. Urodynamic studies comprised measurement of postmicturition residuals, EMG cystometry, and bethanechol injection. Cardiovascular tests included head up tilt test, measurement of supine plasma noradrenaline (norepinephrine,NA), measurement of R-R variability (CV R-R), and intravenous infusions of NA and isoproterenol. Results Urinary symptoms (96%) were found to be more common than orthostatic symptoms (43%) (p<0.01) in patients with MSA, particularly with OPCA (p<0.01) and SND (p<0.01) types. In 53 patients with both urinary and orthostatic symptoms, patients who had urinary symptoms first (48%) were more common than those who had orthostatic symptoms first (29%), and there were patients who developed both symptoms simultaneously (23%). Post-micturition residuals were noted in 74% of the patients. EMG cystometry showed detrusor hyperreflexia in 56%, low compliance in 31%, atonic curve in 5%, detrusor-sphincter dyssynergia in 45%, and neurogenic sphincter EMG in 74%. The cystometric curve tended to change from hyperreflexia to low compliance, then atonic curve in repeated tests. Bethanechol injection showed denervation supersensitivity of the bladder in 19%. Cardiovascular tests showed orthostatic hypotension below -30 mm Hg in 41%, low CV R-R below 1.5 in 57%, supine plasma NA below 100 pg/ml in 28%, and denervation supersensitivity of the vessels (α in 73%; β2 in 60%) and of the heart (β1 in 62%). Conclusion It is likely that urinary dysfunction is more common and often an earlier manifestation than orthostatic hypotension in patients with MSA, although subclinical cardiovascular abnormalities appear in the early stage of the disease. The responsible sites seem to be central and peripheral for both dysfunctions.

To investigate the prognostic value of anti-GM1 antibody.

Beneficial treatment has not been established for chronic sensory ataxic neuropathy associated with Sjögren's syndrome (CSAN-SS). We describe two patients with CSAN-SS who clinically improved in response to D-penicillamine treatment. Their neuropathic symptoms were lessened after D-penicillamine, and the results of electrophysiologic studies support the clinical improvement. D-Penicillamine can be considered a potentially beneficial agent in the treatment of CSAN-SS.

Abstract:  During the final two larval instars, a changing pattern of three Ultraspiracle (Usp) proteins (50.5, 52.5, and 57 kDa) was detected in immunoblots of the dorsal abdominal epidermis of the tobacco hornworm, Manduca sexta, by a monoclonal antibody against Drosophila Usp that was shown to detect MsUsp. The 57- and 52.5-kDa bands were present during the intermolt periods and the 50.5- and 52.5-kDa bands during the molting phases. The antibody detected a nuclear antigen present in epidermis, muscle, fat body, and the central nervous system from the time of hatching. In the epidermis Usp was present in all cell nuclei but was especially prominent in the tormogen and trichogen cells immediately after ecdysis in both the penultimate and final instars. This latter immunoreactivity disappeared within 12 h whereas the remainder of the epidermis retained high levels throughout the feeding period. During the molt immunostaining reappeared in the hair cell nuclei. During the wandering stage at the onset of metamorphosis and just before pupal ecdysis, immunoblots showed high levels of Usp, but nuclei showed little or no staining. This discrepancy is likely due to the loss of one Usp isoform from the nucleus and its dispersal in the cytoplasm in preparation for the appearance of the second isoform.

To characterize the cell-surface antigens expressed in tumour cells derived from bovine leukosis and to determine their cell lineages, the immunophenotypes of the tumour cells from 13 bovine lymphosarcomas were examined with 13 monoclonal antibodies (mAbs). Of 13 cattle with lymphosarcomas, four were identified clinically as having the thymic-type sporadic bovine leukosis (SBL) and one as having the skin-type; two had enzootic bovine leukosis (EBL) and six were untypable. Flow cytometric analysis revealed that the tumour cells from nine cases were of T-cell lineage (BoCD5^+, BoCD2^+ or BoCD2^-) and two were of B-cell lineage (MHC-II^+, BoCD5^+, IgM^+); there were two bovine leukaemia virus-infected cattle (EBL). T-cell tumours appeared to originate from immature (BoCD4^-, BoCD8^-) T cells, but there was no significant relationship between clinical type (EBL, calf-, skin- and thymic-type) and tumour-cell immunophenotype.

cDNA clones encoding the bovine major histocompatibility complex (MHC) class II DQα chain were isolated. One clone, MQ9, encoded a primary translated product of 255 amino acids, with a signal peptide of 23 amino acids and a mature polypeptide of 232 amino acids. A new A2 gene in the DQ subregion of the bovine genome was identified from a comparison of amino acid sequences encoded by class II A genes among several species and the construction of a phylogenetic tree. It was revealed that MQ9 is most closely related to the ovine DQA2 genes among sequences from various mammalian species. By contrast, the BoLA-DQA genes previously isolated are more closely related to ovine DQA1 than to the BoLA-DQA2 gene, and they represent BoLA-DQA1 genes. Thus, the presence of two BoLA A genes, which may be expressed and functional in the bovine, as well as in sheep was confirmed. A large number of amino acids unique to products of DQA2 genes of bovine and ovine origin were identified when the predicted amino acid sequences for both species were compared, and most of the DQA2-specific residues were located in the α1 domain and were conserved with respect to products of DQA1 genes of ruminants. Thus, several characteristics of the bovine DQA genes were found to differ from those of human and rodent genes, despite similarities in gene structure and in nucleotide sequence.Copyright 1995, 1999 Academic Press, Inc.

Two overlapping cDNA clones coding for bovine major histocompatibility complex (MKC) class II antigen DRA chain were isolated and characterized. The full-length cDNA clone, MR1, encoded a primary translated product of 253 amino acids, 24 of which were deduced to be a signal peptide and 229 which formed a mature polypeptide. The amino acid sequences deduced from this clone resembled those of class II A molecules from other species in both size and structure, but no potential consensus site of N-linked glycosylation comparable to those in the human, mouse, rat and swine proteins was found in the α2 domain, as well as ovine and equine DRA molecules. Comparison of amino acid sequences encoded by class II A genes among several species and a dendrogram constructed from these data places the DRAgene and the DQA/DYAgenes on two distinct branches of a phylogenetic tree, with bovine DRAand ovine DRAbeing most similar on the DRAbranch.

Three overlapping cDNA clones coding for the bovine major histocompatibility complex (MHC) class II DRβ chain were isolated. A clone NR1 encoded a primary translated product of 266 amino acids, 29 of which were deduced to form a signal peptide and 237 to form the mature polypeptide. The protein predicted from this cDNA appeared to have all the features expected of an expressed MHC class II molecule. Comparison of the sequences and construction of a phylogenetic tree revealed that NR1 represents a BoLA-DRB3gene and not a BoLA-DRB1or BoLA-DRB2pseudogene. NR1 and ovine sequences exhibited the greatest overall similarity among sequences from various mammalian species, followed by the equivalent human sequences. Indeed, the bovine allele was more closely related to certain ovine alleles than to other bovine alleles. A large number of replacement substitutions were identified when β1 domains encoded by NR1 and each of the 36 distinct BoLA-DRB3alleles were compared, and most of the allelic variations were found in regions that are commonly polymorphic in DRBsequences from different species and correspond to the predicted antigen-recognition sire. Thus, the predicted structure of the unique NR1 allele for BoLA-DRB3further confirms the overall conservation of the product of this locus, as previously established from studies in rodent and man.

cDNAs were isolated fromManduca sextathat encode two isoforms of an ultraspiracle (USP) homologue MsUSP‐1 and MsUSP‐2 with different N‐terminal A/B regions. The MsUSP‐1 cDNA predicts a protein with 97% and 45% amino acid identities in the DNA‐ and ligand‐binding domains respectively to theDrosophilaUSP and 89% overall identity withBombyx moriCF1 (an USP homologue). Northern blot hybridizations with probes specific to MsUSP‐1 and MsUSP‐2 showed transcripts of an approximately equal size (4.5 kb), but with diverse developmental profiles inManducaepidermis during the two final larval instars and the onset of the adult moult. The MsUSP‐1 mRNA was expressed during the intermoult periods, with higher levels around the time of the larval ecdyses and at the onset of wandering behaviour. In contrast, the MsUSP‐2 mRNA was up‐regulated at times of high ecdysteroid titre during the larval moults, when the MsUSP‐1 mRNA disappeared. Together, these conversely regulated isoform mRNAs contribute to the constitutive expression profile of total MsUSP mRNA.

In both nonneurological and Alzheimer brains, we examined the localization of adult T cell leukemia-derived factor (ADF) by immunohistochemistry, that of its mRNA by in situ hybridization, and its semiquantitative mRNA analyses by RT-PCR. Anti-ADF antibody gave positive staining of white matter astrocytes and Schwann cells in the posterior root. Their intense and abundant staining was seen in Alzheimer brains. In situ hybridization for ADF mRNA showed identical signals in the white matter astrocytes. The evidence was also confirmed by RT-PCR analysis. These results suggest that redox regulation may play a role in Alzheimer pathology.

The distribution of subpopulations of lymphocytes in lymph nodes and tumors from cattle with enzootic bovine leukosis (EBL) was examined by immunohistochemistry using a panel of monclonal antibodies against leukocyte differentiation molecules of EBL. The lesions in lymph nodes could be divided into three types based on the extent of infiltration and proliferation of neoplastic cells with provirus and differential expression of leukocyte differentiation molecules. The number of B-B2+, sIgM+cells was reduced in frequency in follicles during the neoplastic cell proliferation. CD4- and CD8-positive α/β T cells and γ/δ T cells positive for WC1 (workshop cluster designation) were also reduced in frequency in areas infiltrated with neoplastic cells. Almost all neoplastic cells were B-B2- and IgM-positive. However, there were a few B-B2- and/or IgM-negative cells or cells stained faintly in all cases. WC1+cells were not observed in tumor tissues. However, CD4+and CD8+cells were observed throughout tumor tissues, suggesting a role for these cells in tumor immunity.

Immunohistochemistry and flow cytometric analysis were used with monoclonal antibodies to examine the phenotype of neoplastic cells from cattle with sporadic bovine leukosis (three cases of calf form, two cases of thymic form, and three cases of intermediate form). Three cases of calf form and two cases of intermediate form were positive for B cell lineage in immunohistologic examination and in flow cytometric analysis for B-B2+, sIgM+, and major histocompatibility class II+. Two cases of thymic form and one case of intermediate form were CD2+, CD5+, CD6+, and CD8+in immunohistologic examination and in flow cytometric analysis. The results show that neoplastic cells develop from B and T cell lineages in sporadic bovine leukosis.

The effects of pharmacological intervention on brain muscarinic cholinergic receptor (mAChR) binding were assessed in seven patients with Parkinson's disease by positron emission tomography and carbon-11 labelled N-methyl-4-piperidyl benzilate ([11C]NMPB). [11C]NMPB was injected twice, approximately 2 hours apart, in each patient, to assess the effect of single doses of 4 mg of trihexyphenidyl (n=5) or 400 mg of L-dopa with 57 mg of benserazide (n=2) on the binding parameter of mAChRs (K3). There was a mean 28% inhibition of K3 values in the brain in the presence of trihexyphenidyl, which was assumed to reflect mAChR occupancy. No significant change in K3 was observed in the presence of L-dopa. This study demonstrates the feasibility of measuring mAChR occupancy by an anticholinergic medication with PET.

Objectives To assess muscarinic acetylcholine receptors (mAChRs) in the brains of patients with progressive supranuclear palsy and Parkinson's disease, and to correlate the cholinergic system with cognitive function in progressive supranuclear palsy and Parkinson's disease. Methods Positron emission tomography (PET) and [¹¹C]N-methyl-4-piperidyl benzilate ([¹¹C]NMPB) was used to measure mAChRs in the brain of seven patients with progressive supranuclear palsy, 12 patients with Parkinson's disease, and eight healthy controls. All of the patients with progressive supranuclear palsy were demented. The Parkinson's disease group consisted of 11 non-demented patients and one demented patient. The mini mental state examination (MMSE) was used to assess the severity of cognitive dysfunction in all of the subjects. The modified Wisconsin card sorting test (WCST) was used to evaluate frontal cognitive function in the non-demented patients with Parkinson's disease and controls. ResultsThe mean K ₃ value, an index of mAChR binding, was significantly higher for the frontal cortex in the patients with Parkinson's disease than in the controls (p<0.01). By contrast, the patients with progressive supranuclear palsy had no significant changes in the K ₃ values of any cerebral cortical regions. The mean score of the MMSE in the progressive supranuclear palsy group was significantly lower than that in the control group. Although there was no difference between the Parkinson's disease and control groups in the MMSE, the non-demented patients with Parkinson's disease showed significant frontal lobe dysfunction in the WCST. ConclusionsThe increased mAChR binding in the frontal cortex of the patients with Parkinson's disease may reflect denervation hypersensitivity caused by loss of the ascending cholinergic input to that region from the basal forebrain and may be related to frontal lobe dysfunction in Parkinson's disease. The cerebral cortical cholinergic system may not have a major role in cognitive dysfunction in progressive supranuclear palsy.

Summary The lattice modes of polyethylene with the phase differences (? andF along thea-axis and theb-axis were calculated at intervals of 30‡ for the phase differences. They wereTx, Ty, T'x, T'y, R'z andR'z, and some special conditions of the phase differences separated the six modes. To know the reliability of the intermolecular force constants used in this calculation, the elastic moduli of polyethylene crystal along thea-axis and theb-axis were calculated with the modified potential functions and compared with the observed values.

We obtained micturitional histories and performed urodynamic studies in six patients with pure autonomic failure. All patients had urinary symptoms. Urodynamic studies showed postmicturition residuals in two, small bladder capacities in two, detrusor hyperreflexia in four, low bladder compliance in two, detrusor-external sphincter dyssynergia in one, neurogenic sphincter electromyography in three, and denervation supersensitivity of the bladder in two. Micturitional disturbance is a common feature in pure autonomic failure because of peripheral and central types of abnormalities.

The synthesis of various tri‐ and tetrafunctional carbon compounds such as (III), (IV) or (VI) is described.