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The importance of emotional and social isolation to loneliness among very old rural adults.

The purpose of this study was to determine the relative importance of emotional and social isolation to loneliness among very old rural adults. The sample (N = 119) was selected using a compact area cluster sampling design. Multiple regression analysis showed that emotional isolation--more specifically, the loss of spouse--accounted for more loneliness than social isolation. Hearing acuity and visits with siblings (social isolation variables) were also significant predictors of loneliness. The implications for loneliness interventions are discussed.

Aged↗

Comparative genomics of vertebrate Fox cluster loci.

BACKGROUND: Vertebrate genomes contain numerous duplicate genes, many of which are organised into paralagous regions indicating duplication of linked groups of genes. Comparison of genomic organisation in different lineages can often allow the evolutionary history of such regions to be traced. A classic example of this is the Hox genes, where the presence of a single continuous Hox cluster in amphioxus and four vertebrate clusters has allowed the genomic evolution of this region to be established. Fox transcription factors of the C, F, L1 and Q1 classes are also organised in clusters in both amphioxus and humans. However in contrast to the Hox genes, only two clusters of paralogous Fox genes have so far been identified in the Human genome and the organisation in other vertebrates is unknown. RESULTS: To uncover the evolutionary history of the Fox clusters, we report on the comparative genomics of these loci. We demonstrate two further paralogous regions in the Human genome, and identify orthologous regions in mammalian, chicken, frog and teleost genomes, timing the duplications to before the separation of the actinopterygian and sarcopterygian lineages. An additional Fox class, FoxS, was also found to reside in this duplicated genomic region. CONCLUSION: Comparison of loci identifies the pattern of gene duplication, loss and cluster break up through multiple lineages, and suggests FoxS1 is a likely remnant of Fox cluster duplication.

Animals↗

Schwann cell remyelination of demyelinated axons in spinal cord multiple sclerosis lesions.

To investigate remyelination in multiple sclerosis lesions, we immunostained spinal cord sections from patients with multiple sclerosis and neurological normal (control) patients with antisera to P0 protein, a major constituent of peripheral nervous system myelin, and myelin basic protein, which is found in both central and peripheral nervous system myelin. In sections from five of the eight patients with no clinical or pathological evidence of neurological disease, P0 immunostaining was confined to peripheral myelin sheaths in dorsal and ventral roots. They were intensely stained, and peripheral--central nervous system transition zones were clearly demarcated. Sections from the other three control patients contained a few P0-stained sheaths in the central nervous system near root entry zones or among marginal glia near the dorsal sulcus. Spinal cord sections from six of the ten patients with multiple sclerosis contained clusters of myelin sheaths immunostained by P0 antiserum. These regenerating sheaths of peripheral nervous system origin were most numerous in large lesions and were commonly located in central areas or peripherally near root entry zones. The sheaths were observed frequently in areas of active demyelination and appeared morphologically normal even when surrounded by debris-filled macrophages. Near margins of small inactive plaques were a few basic protein--stained oligodendroglia extending processes to thin basic protein--stained sheaths.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Comparing multiple RNA secondary structures using tree comparisons.

In a previous paper, an algorithm was presented for analyzing multiple RNA secondary structures utilizing a multiple string alignment algorithm. In this paper we present another approach to the problem of comparing many secondary structures by utilizing a very efficient tree-matching algorithm that will compare two trees in O([T1] X [T2] X L1 X L2) in the worst case and very close to O([T1] X [T2]) for average trees representing secondary structures. The result of the pairwise comparison algorithm is then used with a cluster algorithm to produce a multiple structure clustering which can be displayed in a taxonomy tree to show related structures.

Algorithms↗

[Management of hyperuricemia in occupational health: with reference to "guidelines for the management of hyperuricemia and gout"].

In 1996, the need for the clinical guidelines for the management of hyperuricemia and gout was proposed of the consensus conference held at the 29th annual meeting of the Japanese Society of Purine and Pyrimidine Metabolism (president Yuji Matsuzawa). At the consensus conference, the following announcement was made. 1. Because the majority of patients with hyperuricemia are in the condition of multiple risk factor clustering syndrome, hyperuricemia per se should be counted as one of the typical lifestyle related diseases. 2. Medical management should be directed independently for the treatment of gouty arthritis and for control of the serum uric acid level. 3. The serum uric acid level should be taken into account as a possible cardiovascular risk factor. 4. Urine alkalization should be started if there is no symptom indicating hyperuricemia for the prophylaxis of urinary stones and renal dysfunction. 5. All the medical management should be considered under the consensus of the many expert physicians dealing with hyperuricemia and gout. This principal announcement was made by the consensus conference and the simple management recommendation of a 6-7-8 rule was proposed through the consensus of expert physicians. Recently, a guideline committee was organized in the Japanese Society of Gout and Nucleic Acid Metabolism (previous by the Japanese Society of Purine and Pyrimidine Metabolism) and the Guidelines for the Management of Hyperuricemia and Gout were prereleased in February and published in August 2002. In the new guidelines, the above policy was introduced and evidence was collected to give the guidelines contemporary clinical usefulness and value. It will help in the proper management of hyperuricemia in apparently healthy persons in occupational health, having multiple risk factors.

Arteriosclerosis↗

Identification of proximal and distal regulatory elements of the rat connexin32 gene.

We have investigated the genetic basis of the transcriptional regulation of the rat connexin32 gene which encodes the major gap junction protein in rat liver. Primer extension analysis of RNA isolated from adult rat liver identified multiple initiation sites clustered between -110 bp and -50 bp upstream from the translation start codon. An approx. 760 bp genomic DNA fragment upstream of the first exon which included the mRNA start sites was cloned 5' to the luciferase reporter cassette in p19LUC to yield pCx32-800/-33-LUC. Transfection of pCx32-800/-33-LUC resulted in a 200-fold increase in luciferase activity above p19LUC in the human hepatoma cell line HuH-7. Using a series of vectors containing 5' deletions of the 760 bp fragment, a basal promoter was localized between -179 bp and -134 bp. Three DNA:protein complexes were identified with the basal promoter fragment by DNA mobility shift assay using nuclear extracts from HuH-7 cells. Two of the DNA-binding complexes appeared to be related to the transcription factor Sp1. In addition, three DNase hypersensitive (HS) sites were identified within the genomic locus of connexin32 in adult rat liver. Two of the DNase HS regions behaved as silencer elements with both the native promoter and a heterologous promoter in HuH-7 cells. These data demonstrate that (1) the active promoter responsible for rat connexin32 mRNA transcription is located upstream of the first exon, (2) a basal promoter region was localized to a 50 bp region which formed multiple DNA:protein complexes, and (3) multiple proximal and distant regulatory elements are involved in the expression of connexin32.

Animals↗

Localization of grey matter atrophy in early RRMS : A longitudinal study.

Previous MR studies have established that grey matter (GM) atrophy occurs in multiple sclerosis (MS) from clinical onset. However, it is uncertain whether early GM atrophy is global or has certain local predilections: using Voxel-Based Morphometry this study aimed to address this question.Twenty-one patients with early RRMS (mean age 36 years, mean disease duration from symptom onset 25.8 months) and 10 healthy control subjects (mean age 37 years) were studied. T(1)-weighted three-dimensional MRI images were acquired at baseline and two year follow-up, and analysed with statistical parametric mapping software (SPM2). Two-sample t-tests (p < 0.05 corrected for multiple comparisons at cluster level) were used to compare GM maps from all patients and controls on a voxel-by-voxel basis. At baseline, no GM region appears significantly atrophic in MS subjects compared with controls. However, during the follow-up period significantly greater atrophy occurred in both thalami and the right lateral prefrontal cortex of MS patients when compared with controls. By year two, cross-sectional group comparison revealed GM atrophy in the thalami of MS patients relative to controls. The rate of thalamic atrophy in MS subjects was correlated with changes in EDSS during the follow-up period. This study suggests that early in the clinical course of RRMS, the thalamic atrophy is more consistently apparent than regional cortical atrophy.

Adult↗

Clustering individuals as a way of dealing with multiple predictors in occupational stress research.

As the number and type of variables thought to affect the amount of stress experienced by an individual in the workplace increase, and as these effects are often found to be nonlinear and to interact with each other, the forms of statistical analyses employed present different costs and benefits. The use of cluster analysis as a preliminary means of categorizing individuals is described as the least artificial and empirically most accurate means of deriving groups that can lead to hypotheses and hypothesis testing using the more conventional means of analysis of variance. Such a methodology is described as it was applied to an investigation of the effects of demands, attitudes to demands, supports-constraints, and trait neuroticism upon job satisfaction and scores on the General Health Questionnaire for a sample of psychiatric nurses.

Affective Symptoms↗

Deterring sales and provision of alcohol to minors: a study of enforcement in 295 counties in four states.

The authors analyzed patterns of criminal and administrative enforcement of the legal minimum age for drinking across 295 counties in four States. Data on all arrests and other actions for liquor law violations from 1988 through 1990 were collected from the Federal Bureau of Investigation Uniform Crime Reporting System, State Uniform Crime Reports, and State Alcohol Beverage Control Agencies. Analytic methods used include Spearman rank-order correlation, single-linkage cluster analysis, and multiple regression modeling. Results confirmed low rates of enforcement of the legal drinking age, particularly for actions against those who sell or provide alcohol to underage youth. More than a quarter of all counties examined had no Alcoholic Beverage Control Agency actions against retailers for sales of alcohol to minors during the three periods studied. Analyses indicate that 58 percent of the county-by-county variance in enforcement of the youth liquor law can be accounted by eight community characteristics. Rate of arrests for general minor crime was strongly related to rate of arrests for violations of the youth liquor law, while the number of law enforcement officers per population was not related to arrests for underage drinking. Raising the legal age for drinking to 21 years had substantial benefits in terms of reduced drinking and reduced automobile crashes among youths, despite low level of enforcement. Potential benefits of active enforcement of minimum drinking age statutes are substantial, particularly if efforts are focused on those who provide alcohol to youth.

Adolescent↗

The application of multifactorial cluster analysis in the staging of plaques in early multiple sclerosis. Identification and characterization of the primary demyelinating lesion.

Tissues from 13 exceptionally early cases of multiple sclerosis were studied to identify and characterize the primary demyelinating lesion, using a variety of histological and immunocytochemical methods. Multifactorial cluster analysis identified five significantly distinct lesion groups, which showed histological progression from simple microglial lesions, predominating in tissues from the earliest cases, to complex hypercellular fully demyelinated plaques, chiefly associated with cases of intermediate duration. Quiescent lesions showing evidence of remyelination were found at all stages of the disease studied, but hypocellular inactive plaques, were associated with older cases. Evidence is presented that initial demyelination is effected by activated resident microglia. Undegraded myelin is initially enveloped by membranes bearing fixed complexes of immunoglobulin and complement. In contrast with perivenous encephalomyelitis, in which demyelination was dominated by T-cell infiltration, multiple sclerosis lesions of comparable duration and maturity exhibited humoral immune reactions. Parenchymal CD4+ T-cell infiltration developed in association with subsequent plaque maturation. These results emphasize the need for lesion staging when multiple sclerosis tissues are being used in the investigation of pathogenic mechanisms, and suggest that further analysis of the oligoclonal B-cell response may be productive in the search for primary provoking antigens.

Adult↗

Cytoarchitecture of sensorimotor areas in the cat cerebral cortex.

The organization of multiple motor areas in the cerebral cortex has been investigated frequently in primates but rarely in nonprimate species. To compare sensorimotor areas in cats and primates, the cytoarchitecture of frontal and parietal areas of the cat cerebral cortex was described and mapped from coronal sections stained with cresyl violet or thionine. Multiple subdivisions of areas 4 and 6 were recognized; of these, the cytoarchitecture of area 4 gamma is similar to that of area 4 described in other carnivores and in primates and is characterized by giant pyramidal cells in multiple rows or clusters in lamina V. In other subdivisions of area 4 (4 delta, 4sfu, and 4fu), giant pyramidal cells are few or absent in lamina V, and these subdivisions resemble area 6 of primates. Area 6 of the cat cortex is heterogeneous, and differences in laminar appearance and size of pyramidal cells in lamina V distinguish its four subdivisions (6a alpha, 6a beta, 6a gamma, and 6iffu). The adjoining prefrontal areas are distinguishable from area 6 by the presence of a thin internal granular lamina (lamina IV) and the reduced size of pyramidal cells in lamina V. Laminae are poorly differentiated in the cingulate areas, where a rostral and caudal subdivision can be distinguished on the basis of the absence or presence of lamina IV. Area 3a is characterized by a thin lamina IV and is located between frontal agranular and parietal granular (well-defined lamina IV) fields (3b, 1, 2, 2pri, 5, and 7). Insular cortex can be subdivided into granular and agranular fields.

Animals↗

Organization of the face representation in macaque motor cortex.

We stimulated with microelectrodes the face representation in precentral motor cortex in macaque monkeys. Responses were very discrete; at threshold current levels the usual response was a small focus of movement in part of a muscle. Facial muscles cluster together in the posterior and anterior portions of the precentral gyrus with tongue movements represented in the intervening region and along the lateral extent. Within each cluster there are multiple representations of individual muscle movements. In long penetrations down the anterior wall of the central sulcus we were able to advance the electrode tangentially through cortex. In these penetrations we encountered a series of discrete zones each of which was related to the movement of a particular muscle or part of a muscle in the face. The lowest threshold points were found in the center of each zone, and as the microelectrode progressed toward the edge, thresholds rose until there was a shift to a new muscle movement. Successive stimulation points separated by as little as 50 micrometer could yield different responses. These zones could be either roughly cylindrical or take the form of narrow curving bands running mediolaterally across cortex. There is a tendency for adjacent muscles to occur together, and the representation may be roughly topographical within the limits set by the morphological structure of the muscles themselves. The most commonly evoked muscle response was in zygomaticus, which retracts the corners of the mouth in expressions of fear and anger.

Animals↗

The t(15;17) translocation alters a nuclear body in a retinoic acid-reversible fashion.

Nuclear bodies (NBs) are ultrastructurally defined granules predominantly found in dividing cells. Here we show that PML, a protein involved in the t(15;17) translocation of acute promyelocytic leukaemia (APL), is specifically bound to a NB. PML and several NB-associated proteins, found as auto-antigens in primary biliary cirrhosis (PBC), are co-localized and co-regulated. The APL-derived PML-RAR alpha fusion protein is shown to be predominantly localized in the cytoplasm, whereas a fraction is nuclear and delocalizes the NB antigens to multiple smaller nuclear clusters devoid of ultrastructural organization. RA administration (which in APL patients induces blast differentiation and consequently complete remissions) causes the re-aggregation of PML and PBC auto-antigens onto the NB, while PML-RAR alpha remains mainly cytoplasmic. Thus, PML-RAR alpha expression leads to a RA-reversible alteration of a nuclear domain. These results shed a new light on the pathogenesis of APL and provide a molecular link between NBs and oncogenesis.

Animals↗

Prevention of X-ray-induced late dermal necrosis in the pig by treatment with multi-wavelength light.

Low-level light from a multi-wavelength array of light sources has been used to prevent late X-ray-induced dermal necrosis in the pig. Skin fields, measuring 4 x 4 cm on the flank, were irradiated with a single dose of 23.4 Gy of X-rays. This X-ray dose was associated with the development of a 100% incidence of dermal necrosis, 10-16 weeks after irradiation. These irradiated skin sites were subsequently exposed to light of 660, 820, 880, and 950 nm wavelengths from a gallium aluminium arsenide multiple wavelength multidiode cluster probe (Biotherapy Medical Laser, 3ML), three times a week, from 4 to 16 weeks or 6 to 16 weeks after X-irradiation. The skin fields were exposed to the light pulsating at either 2.5 Hz or 5 kHz. With light pulsating at 5 kHz, energy densities of 0.22, 0.54, 1.08 2.16, 4.32, and 10.8 J/cm2 were used. Treatment with light pulsating at 2.5 Hz, 6-16 weeks after X-irradiation, or treatment with light pulsating at 5 kHz, 4-16 weeks after X-irradiation, did not have a significant effect on the incidence or the latency for the development of ischemic dermal necrosis irrespective of the exposure time to light at each treatment. With light pulsating at 5 kHz, no effect of light dose was observed. However, the overall incidence of dermal necrosis was significantly reduced (P = 0.001) to 52% in the X-irradiated fields receiving treatment with 5 kHz light, 6-16 weeks after X-irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Origin and initiation sites of lambda dv DNA replication in vitro.

The sequence of lambda DNA essential for the unique initiation of replication was analyzed in an in vitro replication system. Fragments of lambda DNA were inserted into pBR322 and used as templates or were circularized in vitro in the absence of pBR322 and employed in the same tests. A 165-bp region left of the EcoRI site in the O gene of the lambda genome was defined as the functional origin. This region, which we defined as the ori region, carries, in order, the 4 19-bp repeat sequences where the O protein binds (ori-repeats), an A+T-rich stretch, and a region that constitutes part of a large palindromic structure. Regions that have long been suspected to participate in lambda DNA replication initiation, ice and oop were not required for the O, P-dependent lambda-specific replication initiation. The lambda dv and the "ori region plus" recombinant plasmids initiated DNA synthesis at or around this region, and the reaction depended on the presence of lambda-coded initiators, O and P proteins. Early replicative intermediates of lambda dv were prepared in an in vitro replication system in the presence of ddCTP, an inhibitor of DNA chain elongation. This system allows only that DNA synthesis that is a result of replication initiation. Using this system, the initiation site(s) of the DNA synthesis was finely analyzed by mapping the transition sites from primer RNA to DNA synthesis. Short-chain DNAs produced from regions near the ori region were purified from the intermediates. A fraction of the short-chain DNAs was covalently linked to primer RNA. The 5'-ends that had been linked to RNA (transition sites) were exposed by alkaline hydrolysis, labeled with 32P, and the transition sites were mapped along the nucleotide sequence of the genome. Two striking features emerged from this analysis: (i) The transition sites are located on both sides of the ori region, and no transition arose within the 165-bp ori region; (ii) The transition sites on both sides are not unique, but multiple, and are clustered in one of the 2 strands. Furthermore, their orientation demonstrates that the DNA synthesis in initiation of replication from the 2 sides of the ori region converge. The frequency of the "leftward" DNA synthesis is several times higher than that of "rightward" synthesis. These results reflect asymmetric bidirectional replication of lambda dv DNA, and may also reflect replication of lambda phage DNA.

Bacteriophage lambda↗

Tetanus toxin channel in phosphatidylserine planar bilayers: conductance states and pH dependence.

Tetanus toxin (TeTx) forms ionic channel in phosphatidylserine bilayers. TeTx channels exhibit different modes of channel bursting activity, from a closed state to well defined open states of different amplitudes. At positive applied voltages, TeTx channels flicker continuously between a closed state and the various distinct open states. Furthermore, fast transitions into subconductance states are discernible within the bursts of channel activity. Elementary conductance steps submultiple of the open states were not identified in single channel records owing to rapid transitions between different states. However, statistical analysis shows that conductances cluster with amplitudes multiple of an elementary value: e.g. 25-30 pS at neutral pH. Single channel current amplitudes decrease with the pH of the bulk electrolyte solution. Conductance decrements can be accounted for by the relative decrease of permeant cation concentration at the membrane-water interface, by a relative enrichment of protons that block the channel or by the stabilization of a conformational state of the channel protein.

Hydrogen-Ion Concentration↗

The human muscle-tendon junction. A morphological study during normal growth and at maturity.

The myotendon junction of human paravertebral skeletal muscle was studied by light and electron microscopy. Transverse and longitudinal sections of myotendinous regions of normal multifidus muscles were examined at three chronological stages from birth to maturity. Variations in the appearance of surface extensions at the terminal ends of muscle fibers consisted of brush-like evaginations at birth and villous-like projections in the adult. Regardless of age, they were invariably covered by a prominent external lamina, and mutually interdigitated with connective-tissue elements in the adjacent tendon. Various stages of myofibrillar assembly and sarcomere alignment were evident in the muscle fiber terminus at birth. With advancing age, splitting of terminal sarcomeres at Z bands commonly gave rise to diverging myofilament bundles that attached to electron-dense patches under the sarcolemma. In these regions, leptomeric organelles were also encountered in neonatal and adolescent myotendons. At all stages, the ends of muscle fibers possessed cytological features consistent with active synthesis and secretion. Densely-packed sarcoplasmic organelles including multiple Golgi complexes, clusters of ribosomes, mitochondria, cytoplasmic vesicles, and elements of rough- and smooth-surfaced endoplasmic reticulum were prevalent. Peripheral and centrally-placed heterochromatic nuclei with prominent nucleoli were arranged singly or in groups at the ends of muscle fibers. Satellite cell profiles and unmyelinated axons in the subjacent tendon were also identified at these sites in the adult. Fibroblasts in growing tendon were plentiful, and at all stages, possessed morphological features indicative of high metabolic and secretory activities.

Adolescent↗

[Morphology versus prognosis in renal cell carcinoma a statistical approach].

In a group of 102 selected cases of renal cell carcinoma which at various periods after nephrectomy terminated fatally, age, sex, and 23 gross and/or histologic tumor characteristics were examined, subclassified, and evaluated. An attempt was made to correlate these parameters statistically to postoperative survival time. A newly developed and programmed statistical method, i.c. "dichotomic variance analysis", proved to be superior to both multiple regression and cluster analysis. Using infiltrative-destructive tumor growth, polymorphy, and chromatin density of tumor cell nuclei, extension of renal vein invasion, age and sex, as the only 6 required out of 25 distinguished tumor parameters, this statistical multivariate method comprised 7 distinctive groups of different mean geometrical postoperative survival time, obviously corresponding to 7 tumor types of increasing degree of malignancy. By step-wise dichotomic splitting of tumor groups it therefore was possible to delinate schematically some of the complex connections between the criteria or variables of prognostic significance. Conceivable sources of errors possibly influencing reproducibility and practical applicability of the presented dichotomic variance analysis in evaluating prognostic criteria in renal cell carcinoma are discussed.

Adult↗