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PubMed1985

Pili of Neisseria meningitidis. Analysis of structure and investigation of structural and antigenic relationships to gonococcal pili.

To provide information useful for the design of a pilus vaccine effective for the prevention of both meningococcal and gonococcal disease, the electron microscopic morphology of meningococcal pili and the structural and antigenic relationships of meningococcal pili to gonococcal pili were investigated. Meningococcal pili were 4-6 nm in width, extended 500-6,000 nm from the organism surface, and occurred singly or in bundles composed of 8-10 pili per bundle. Meningococcal pilin varied between 17,250 and 20,600 daltons. Pilin was present in outer membrane preparations of some meningococcal isolates that were nonpiliated by electron microscopic examination. Antibodies to gonococcal pili, cyanogen bromide cleavage fragments of gonococcal pilin, or synthetic peptide analogues corresponding to regions of the gonococcal pilin sequence, were used to detect common meningococcal and gonococcal antigenic determinants that might indicate the existence of a conserved sequence beyond residue 29. Antibody to intact gonococcal pili or to the variable CNBR-3 region of gonococcal pilin detected little shared antigenicity with meningococcal pilin. However, pilin from all tested meningococcal isolates reacted with antibody to the CNBR-2 fragment of gonococcal pilin, a region highly conserved among gonococcal strains. Meningococcal pilins were also broadly crossreactive with antibody to a synthetic peptide corresponding to residues 69-84 of the gonococcal sequence, a part of the CNBR-2 region that appears to be critical for gonococcal receptor-binding function. If a sequence similar to 69-84 is also important for receptor-binding function in meningococcal pili, a peptide corresponding to this region may elicit antibodies that block the adherence function of pili elaborated by both Neisseria gonorrhoeae and N. meningitidis.

Amino Acid Sequence↗

PubMed2001

Gating kinetics of the alpha1I T-type calcium channel.

The alpha1I T-type calcium channel inactivates almost 10-fold more slowly than the other family members (alpha1G and alpha1H) or most native T-channels. We have examined the underlying mechanisms using whole-cell recordings from rat alpha1I stably expressed in HEK293 cells. We found several kinetic differences between alpha1G and alpha1I, including some properties that at first appear qualitatively different. Notably, alpha1I tail currents require two or even three exponentials, whereas alpha1G tails were well described by a single exponential over a wide voltage range. Also, closed-state inactivation is more significant for alpha1I, even for relatively strong depolarizations. Despite these differences, gating of alpha1I can be described by the same kinetic scheme used for alpha1G, where voltage sensor movement is allosterically coupled to inactivation. Nearly all of the rate constants in the model are 5-12-fold slower for alpha1I, but the microscopic rate for channel closing is fourfold faster. This suggests that T-channels share a common gating mechanism, but with considerable quantitative variability.

Action Potentials↗

PubMed1978

Specific immune recognition by lymphocytes: an evolutionary perspective.

In this review, we analyze data pertinent to the origins of specific immune recognition by lymphocytes. The phenomena of immunity in invertebrates and the cells that might be involved in these processes are considered. We conclude that the existence of vertebrate-type immunocompetent lymphocytes in invertebrates is not yet proven. All vertebrates apparently possess immunologically competent lymphocytes, and the following conclusions may be drawn: (1) Specific antigen recognition by lymphocytes of all vertebrates appears to be mediated by membrane-bound immunoglobulins. These immunoglobulins are, in all probability, distinct from secreted, serum immunoglobulins (antibodies), although serum and surface immunoglobulins share combining sites for antigen which are formed of variable regions. (2) There is evidence for similar functional divisions among the immune systems of all vertebrates, as reflected in the results of anatomical, functional, and physicochemical investigations of lymphocytes from animals as diverse as fish and mammals.

Adaptation, Biological↗

PubMed2002

Temporal trends in the incidence of human immunodeficiency virus infection and risk behavior among injection drug users in Baltimore, Maryland, 1988-1998.

Although the incidence of and mortality from acquired immunodeficiency syndrome have declined recently in the United States, data are needed on the incidence of human immunodeficiency virus (HIV) and risk behaviors among injection drug users (IDUs). The authors studied the temporal trends of HIV incidence and risk behavior, ascertained through semiannual confidential interviews, between 1988 and 1998 in a cohort of 1,532 HIV-seronegative IDUs in Baltimore, Maryland. An additional 338 HIV-negative drug users were recruited in 1994 and were studied by using the same methods. Overall, 277 persons seroconverted to HIV during 8,826.45 person-years of follow-up, an incidence of 3.14 per 100 person-years. The incidence per 100 person-years declined over time from 4.45 in 1988-1990 to 3.35 in 1991-1994 to 1.84 in 1995-1998, a decline of 12% per year. HIV infections were associated with injection of cocaine, more frequent injection, needle sharing, and injection in a shooting galley. Sexual behavior variables associated with HIV incidence included a sexually transmitted infection, male homosexual behavior, and sex with another IDU. These data suggest that high-risk behavior and HIV incidence among IDUs have decreased recently in Baltimore. Nevertheless, additional prevention strategies are needed in these populations.

Adult↗

PubMed2006

Unraveling helicase mechanisms one molecule at a time.

Recent years have seen an increasing number of biological applications of single molecule techniques, evolving from a proof of principle type to the more sophisticated studies. Here we compare the capabilities and limitations of different single molecule techniques in studying the activities of helicases. Helicases share a common catalytic activity but present a high variability in kinetic and phenomenological behavior, making their studies ideal in exemplifying the use of the new single molecule techniques to answer biological questions. Unexpected phenomena have also been observed from individual molecules suggesting extended or alternative functionality of helicases in vivo.

Base Pairing↗

PubMed1992

Differences in the prevalence of hypertension by ethnic origin and age at immigration in a cohort of 5,146 Israelis.

Marked ethnic differences in hypertension prevalence have been described in Jewish immigrants to Israel. The extent to which this phenomenon has persisted after a long period of living in the same country, and whether native-born descendants exhibit similar patterns, is not clear. The aim of this study was to determine the prevalence of hypertension in immigrants to Israel and native-born Israelis by region of origin and age at immigration. Complete data were available for 5,146 subjects (3,607 men and 1,539 women) aged 20-64 years who were employed in Israeli industries and were examined during 1985-1987. In both sexes, Jews originating in the West (Europe and the Americas) had higher blood pressures and a significantly higher prevalence of hypertension than those from northern Africa or Asia, particularly in the age group 20-44 years (17% vs. 9% and 8% in men, respectively, and 9% vs. 3% and 5% in women). There was a significant positive association between the prevalence of hypertension and age at immigration (p less than 0.001) in both sexes, and this finding was present in all ethnic groups. In multiple logistic regression analysis, the associations of hypertension with ethnic origin and age at immigration were only partly explained by variations in body mass index, after controlling for other potentially confounding variables. These findings suggest that despite these subjects' having shared a relatively similar physical environment for many years, ethnic differences in the prevalence of hypertension persist. Immigration at an older age was associated with a higher prevalence of hypertension for both subjects originating in industrialized countries and those originating in nonindustrialized countries, suggesting that the process of immigration itself may adversely affect blood pressure.

Adult↗

PubMed2003

The potential public health and community impacts of safer injecting facilities: evidence from a cohort of injection drug users.

BACKGROUND: Although medically supervised safer injecting facilities (SIFs) remain untested in North America, their implementation is currently being debated. Reluctance of health policy makers to initiate a pilot study of SIFs may in part be hindered by outstanding questions regarding the potential community and public health impact of the intervention. Specifically, it is presently unknown if those at greatest risk of overdose and HIV transmission or those responsible for community impact of injection drug use will be willing to attend. METHODS: The current study was conducted to evaluate the proportion of injection drug users (IDU) willing to attend medically supervised SIFs, if they were available, among participants enrolled in the Vancouver Injection Drug User Study (VIDUS). The authors also evaluated factors associated with willingness to use a SIF using univariate and logistic regression analyses. Participants who were followed from June 2001 to June 2002 were eligible for the present analyses. RESULTS: Overall, 587 active IDU responded to a questionnaire during the study period. Among respondents, 215 (36.6%) expressed willingness to attend a SIF. Variables that were independently associated with willingness to attend a SIF in multivariate analyses included having difficulty accessing sterile syringes (adjusted odds ratio [AOR] = 2.07), requiring help injecting (AOR = 1.52), frequently injecting heroin (AOR = 1.81), sex trade work (AOR = 2.02), and injecting in public spaces (AOR = 2.00). CONCLUSIONS: Several variables that have recently been associated with overdose, syringe sharing, HIV and HCV incidence, and community impact of illicit drug use in this setting were associated with willingness to attend medically supervised SIFs. Although the impact of SIFs in North America can only be quantified by scientific evaluation, these data indicate a high potential for immediate community and public health benefits if SIFs were presently available.

Adult↗

PubMed1992

T-cell receptor beta-chain gene rearrangements of T-cell populations expanded from multiple sites of synovial tissue obtained from a patient with rheumatoid arthritis.

In this study T-cell receptor (TcR) beta-chain gene rearrangements of T-cell lines prepared from multiple sites (n = 92) of synovial tissue derived from both knees of a patient with rheumatoid arthritis were analysed. In the majority of T-cell lines, dominant TcR beta-chain gene rearrangements were detected, involving C beta 1 as well as C beta 2. The dominant rearrangement patterns of T-cell lines from different tissue fragments showed significant variability, but some of the DNA restriction fragments were shared by T-cell lines from multiple sites in both knees. The latter observation suggests that identical T-cell clones may be present at different sites in the synovial tissue and in different joints. However, since many T-cell lines yielded different rearrangement patterns, these data also indicate considerable heterogeneity of T cells in the joints. Apart from theoretical implications, this TcR heterogeneity of T cells within an individual patient also has practical consequences for studies on synovial T cells obtained by biopsy.

Aged↗

PubMed1988

The tubulin genes of Trypanosoma cruzi.

The organization of the alpha- and beta-tubulin genes in the genome of Trypanosoma cruzi have been analysed by Southern blotting using tubulin probes derived from Trypanosoma brucei. The tubulin array appears to be more complex in this organism than in other members of the same family. Some tubulin genes are tightly clustered in an alternating (alpha-beta)n array with a basic repeat unit length of 4.3 kb. However, other pairs of alternating alpha- and beta-tubulin sequences appear to be physically separated from the basic group. This finding indicates that the tubulin gene cluster present in T. cruzi is less perfectly conserved than in T. brucei. T. (Herpetosoma) rangeli is similar to T. (Schizotrypanum) cruzi in its tubulin gene organization whereas most of these genes are tandemly clustered in the genome of T. (Trypanozoon) evansi, with a basic repeat unit length of 3.6 kb as previously described for T. (Trypanozoon) brucei. Two overlapping recombinant clones containing T. cruzi tubulin sequences have been isolated from a genomic cosmid library of T. cruzi epimastigotes using the T. brucei tubulin probes. Partial sequencing of the T. cruzi beta-tubulin gene has confirmed its identity and shows more than 70% homology with the sea urchin, chicken and T. b. rhodesiense beta-tubulin reported gene sequences. Analysis of tubulin gene organization through the parasite life cycle does not show evidence of major rearrangements within the repeat unit. Several T. cruzi strains and cloned lines whilst sharing the 4.3-kb tubulin repeat unit, exhibited very variable tubulin gene organization with tubulin probes. These striking differences in the organization of this structural gene among T. cruzi strains and cloned lines suggest that the heterogeneity previously reported in parasite populations may be related to a very dynamic, diploid genome.

Animals↗

PubMed1989

Cyclitic glaucoma.

A series of patients is presented showing the widely variable clinical behaviour of different groups of patients who share the common features of cyclitic glaucoma. These cyclitic glaucomas may be classified: 1. Glaucomatocyclitic crises: unilateral or bilateral. This condition presents acutely, almost always in males with a strong tendency to spontaneous resolution but a liability to subsequent recurrence. Some cases are slow to resolve and may recur frequently. 2. Heterochromic cyclitis: glaucoma infrequently complicates heterochromic cyclitis and then with only a mild rise in intraocular pressure (IOP). 3. Chronic cyclitis: unilateral or bilateral. This is more common in females often presenting with a high rise in IOP which may be difficult to control medically. An insidious form of chronic cyclitis occurs in middle-aged, blue-eyed females, often with sarcoid, and is likely to progress to profound visual loss if unrecognised.

Adolescent↗

PubMed1971

Creation of "amyloid" fibrils from Bence Jones proteins in vitro.

"Amyloid" fibrils have been created from some human Bence Jones proteins by proteolytic digestion under physiologic conditions. These fibrils with an antiparallel, beta-pleated sheet conformation consist of only a portion of the variable region of the immunoglobulin light polypeptide chain and share the physical properties of amyloid fibrils. The relation between amyloidosis and immunoglobulins is thus more firmly established and a pathogenetic mechanism for amyloid fibril formation is suggested.

Amino Acid Sequence↗

PubMed2005

Adverse drug reactions and avalanches: life at the edge of chaos.

Although many reports have described the incidence of adverse drug reactions, none have explained their variable severity or why they happen. Because human physiology shares many of the features of other complex adaptive systems, reactions to drug therapy were examined mathematically for specific patterns to show (1) that the severity of adverse drug reactions follows a distribution seen in other complex adaptive systems, called a power law distribution, and (2) that preventable reactions occurred for reasons fundamentally different from those that underlie the nonpreventable reactions. Two reports detailing adverse drug reaction incidence and severity were evaluated: a meta-analysis of prospective adverse drug reaction studies and a prospective cohort study. Incidence of drug reaction was plotted as a function of severity and fit to an equation. The incidences of overall and nonpreventable drug reaction, plotted as a function of severity, followed a similar power law distribution regardless of sample size or the nature of the population or drugs studied. An exception to this was the preventable reactions, which were described by a different type of equation. Response to pharmacotherapy exhibits many properties of systems with self-organized criticality. An exception to this is the preventable reactions, which seem to be fundamentally different from the nonpreventable ones. These observations suggest that the presence and the distribution of severity of reaction to pharmacotherapy is a consequence of our adaptation as biological systems, and although adverse reactions can be made less frequent, a certain percentage will not be preventable.

Adverse Drug Reaction Reporting Systems↗

PubMed2007

Self-efficacy, values, and complementarity in dyadic interactions: integrating interpersonal and social-cognitive theory.

Dyadic interactions were analyzed using constructs from social-cognitive theory (self-efficacy and subjective values) and interpersonal theory (interpersonal circumplex [IPC] and complementarity). In Study 1, the authors developed a measure of efficacy for interpersonal actions associated with each IPC region--the Circumplex Scales of Interpersonal Efficacy (CSIE). In Study 2, the authors used the CSIE and the Circumplex Scales of Interpersonal Values (which assesses the subjective value of interpersonal events associated with each IPC region) to predict the dominance expressed and satisfaction experienced by members of 101 same-sex dyads trying to solve a murder mystery. Structural equation modeling analyses supported both social-cognitive and interpersonal theory. A social-cognitive person-variable (dominance efficacy) and an interpersonal dyadic-variable (reciprocity) together predicted dominant behaviors. Likewise, both a social-cognitive variable (friendliness values) and an interpersonal variable (correspondence of friendliness efficacy) predicted satisfaction. Finally, both shared performance outcomes and dynamic interpersonal processes predicted convergence of collective efficacy beliefs within dyads.

Adult↗

PubMed1979

Research designs appropriate for service agencies.

The intent of research is to inform co-workers in similar environments of new or varied approaches to problems assumed to be shared. However, narratives of reported studies neglect to identify variables necessary for reproducing environmental contigencies. If the proposition is accepted that service agencies occupy unique environments, then single organism research designs such as ABAB and multiple baseline designs may provide more valuable information than currently accepted research methodologies.

Behavior Therapy↗

PubMedDate not supplied

Furunculosis in a high school football team.

An outbreak of Staphylococcus aureus furuncles (boils) occurred among 26 members of a central Illinois high school football team. A total of 55 boils were reported with a diameter of induration ranging from 0.25 to 6 inches (mean = 1.25 inches). Eighty-nine percent of the boils were located on the extremities, and 70% were known to have developed following a bruise or break in the skin. The development of boils was associated with prior bruises and open wounds. Use of skin lubricant, elbow and forearm pads, whirlpool bath, and athletic tape were also associated with the development of boils, but were not judged to be causal. Rather, these factors most likely reflected attempts to protect areas of compromised skin which were at high risk of developing boils. Lack of hot water and soap for showering may have facilitated the occurrence of the outbreak by discouraging players from showering. Other variables examined, but excluded as important factors, were the sharing of football pads, the sharing of towels, the laundering of athletic clothes, and the position played on the football team.

Contusions↗

PubMedDate not supplied

Trends and variability in individual insurance products in California.

This paper examines recent trends in benefits and premiums for individual health insurance products purchased by Californians. There is much variability in the coverage available in the individual insurance market, with correspondingly wide variability in premiums. Despite concerns about increased consumer cost sharing, the average share of health spending covered by these products has remained constant between 1997 and 2002. Whether this trend can continue in the face of higher health costs is unclear.

California↗

PubMed2006

Sibling influence on alcohol use in a young adult, high-risk sample.

OBJECTIVE: Previous research has found that siblings resemble each other in terms of alcohol use but has not examined sibling influence in young adult or high-risk siblings. The current study tested whether siblings prospectively influenced each other's alcohol use and how gender matching, age differences, and family conflict might moderate such effects. METHOD: Data from sibling pairs (n=169 pairs) in an ongoing longitudinal study of children of alcoholics and matched controls were collected at two time points 5 years apart. RESULTS: Older sibling alcohol use predicted younger sibling alcohol use, even after controlling for membership in a shared peer group and for parental alcoholism. However, moderator variables qualified this effect, such that older sibling influence was significant only among sibling pairs who were of the same gender, closer in age, and from higher conflict families. Younger sibling influence was significant only for sibling pairs close in age, suggesting the presence of reciprocal peer-like effects in this subgroup. CONCLUSIONS: The current study provides evidence for sibling influence on alcohol use into adulthood, but the extent of this influence depends on sibling similarity in age and gender and on levels of family conflict. Implications for family-based theory and intervention efforts are discussed.

Adolescent↗

PubMed2000

Accumulation of clonally related B lymphocytes in the cerebrospinal fluid of multiple sclerosis patients.

The accumulation of B lymphocyte clones in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and patients with other neurological disorders was investigated using PCR technologies. Oligoclonal B cell accumulations were detected in 10 of 10 MS patients, but only in 3 of 10 of the patients with other neurological disorders. Analyses of the Ig V(D)J sequences on the CSF from MS patients disclosed that VH3 and VH4 genes were extensively mutated compared with germline sequences. Moreover, a substantial proportion of the molecular clones analyzed shared the same third CDR of the H chain variable region gene (HCDR3) and the same VH genes, albeit with different numbers and locations of point mutations, thus indicating an ongoing process of intraclonal diversification. A larger number of clonally related VH sequences could be obtained by using a VH3 gene-specific PCR so that genealogical trees depicting the process of diversification could be drawn. Analyses of the Ig V(D)J from the CSF of a patient with viral meningitis and oligoclonal B cell accumulations revealed that VH3 genes were extensively mutated. However, no intraclonal diversification could be observed even using VH3 gene-specific PCR methodologies. Clone-specific PCR and sequencing was used to detect the V(D)J found in the CSF of one MS patient in the PBL of the same patient. Only 1/3 of the V(D)J sequences investigated could be demonstrated in the PBL, indicating that the V(D)J genes utilized by B cells in the CSF are much less represented in the PBL. Collectively, the data suggest that in MS there is a compartmentalized clonal expansion.

Adolescent↗