Search PubMed⌕ Search

Biomedical subjects

C Moore

Publications and source records attributed to C Moore.

At least 55 records · Page 3Linked to original sources

Antibody deficiency syndromes.

Antibodies have a crucial role in protecting against infections, and antibody deficiencies are the commonest primary and secondary immunodeficiencies. Antibody deficiencies may be the only abnormality present in a patient, or they may be present and aggravate the symptoms of various other conditions. Because the presence of an antibody deficiency is difficult to predict from clinical presentation, physicians should perform an evaluation of antibody-mediated immunity, even knowing that, in many cases, the results are normal. When immunizations are included as a part of the evaluation, many patients experience a benefit from enhanced immunity against common pathogens. Some alternative practical approaches to the evaluation of patients with recurrent infections are outlined in Figure 8. Referral to a clinical immunologist can be based on the presence of recurrent infections, a positive family history without prior evaluation by a pediatrician, or abnormal immunologic findings that require an advanced evaluation. In any case, a close collaboration between pediatrician and immunologist likely will result in an accurate diagnosis and better treatment of patients with antibody-deficiency syndromes and their families.

Antibodies↗

A Porphyromonas gingivalis genetic locus encoding a heme transport system.

Porphyromonas gingivalis has been implicated in the onset and progression of periodontitis and the availability of hemin for in vitro growth has been associated with virulence of the bacterium in animal models. We report here the cloning and sequence analysis of a P. gingivalis TonB-linked outer membrane receptor gene tlr. This gene was previously identified as a TonB-linked adhesin gene tla and shown to be essential for growth at low concentrations of hemin. The tlr gene is immediately downstream of four open reading frames (htrABCD) that encode a putative ATP binding cassette transport system with sequence similarlity to heme transport systems of other bacteria. Analysis of P. gingivalis W50 mRNA revealed that the htrABCD genes are cotranscribed similar to hemin transport genes of other bacteria.

ATP-Binding Cassette Transporters↗

Attention and joint attention in preschool children with autism.

Three experiments examined the role of attention in explaining dyadic (child-adult) and triadic (child-adult-object) joint attention difficulties in autism. Experiments 1 and 2 investigated children's ability to orient to an adult's attention bid and to follow the direction of a human or nonhuman cue. Experiment 3 tested ability to disengage and shift attention to objects. Results showed autism-specific difficulties at both dyadic and triadic levels. Children with autism were less responsive than developmentally delayed controls in orienting to attention bids and in following a human head-turn cue yet had no difficulty in shifting attention and were faster overall in orienting to targets. Results suggest a specific developmental delay in which children with autism rely on the presence of objects in the visual field to guide action. The relation between this problem and autistic children's difficulties with human communicative signals is discussed.

Attention↗

Epidemics and percolation in small-world networks.

We study some simple models of disease transmission on small-world networks, in which either the probability of infection by a disease or the probability of its transmission is varied, or both. The resulting models display epidemic behavior when the infection or transmission probability rises above the threshold for site or bond percolation on the network, and we give exact solutions for the position of this threshold in a variety of cases. We confirm our analytic results by numerical simulation.

Epidemiologic Methods↗

Exact solution of site and bond percolation on small-world networks.

We study percolation on small-world networks, which has been proposed as a simple model of the propagation of disease. The occupation probabilities of sites and bonds correspond to the susceptibility of individuals to the disease, and the transmissibility of the disease respectively. We give an exact solution of the model for both site and bond percolation, including the position of the percolation transition at which epidemic behavior sets in, the values of the critical exponents governing this transition, the mean and variance of the distribution of cluster sizes (disease outbreaks) below the transition, and the size of the giant component (epidemic) above the transition.

Disease Outbreaks↗

Posttranslational phosphorylation and ubiquitination of the Saccharomyces cerevisiae Poly(A) polymerase at the S/G(2) stage of the cell cycle.

The poly(A) polymerase of the budding yeast Saccharomyces cerevisiae (Pap1) is a 64-kDa protein essential for the maturation of mRNA. We have found that a modified Pap1 of 90 kDa transiently appears in cells after release from alpha-factor-induced G(1) arrest or from a hydroxyurea-induced S-phase arrest. While a small amount of modification occurs in hydroxyurea-arrested cells, fluorescence-activated cell sorting analysis and microscopic examination of bud formation indicate that the majority of modified enzyme is found at late S/G(2) and disappears by the time cells have reached M phase. The reduction of the 90-kDa product upon phosphatase treatment indicates that the altered mobility is due to phosphorylation. A preparation containing primarily the phosphorylated Pap1 has no poly(A) addition activity, but this activity is restored by phosphatase treatment. A portion of Pap1 is also polyubiquitinated concurrent with phosphorylation. However, the bulk of the 64-kDa Pap1 is a stable protein with a half-life of 14 h. The timing, nature, and extent of Pap1 modification in comparison to the mitotic phosphorylation of mammalian poly(A) polymerase suggest an intriguing difference in the cell cycle regulation of this enzyme in yeast and mammalian systems.

Cell Cycle↗

Drinking patterns and problems of the "stably insured": a study of the membership of a health maintenance organization.

OBJECTIVE: This article describes drinking patterns and examines the prevalence of heavy drinking and alcohol problems, and their association with other behavioral and social problems within the membership of a health maintenance organization, a setting in which increasing numbers of Americans receive services. METHOD: The sample is representative of the stably insured membership of the Northern California Region of Kaiser Permanente Medical Care Program; i.e., those who have been insured continuously under that plan for 30 months or longer. A telephone survey of the adult membership (N = 10,292) was conducted between June 1994 and February 1996. RESULTS: As in other studies, health and mental health status and smoking were related to drinking levels, with symptoms higher for those in the heaviest drinking group. However, in contrast to studies of those using medical services, demographic characteristics (e.g., young age) were not associated with heavy drinking in this population. When controlling for drug use and drinking, however, women and those reporting any mental health symptom were more likely to report alcohol problems. CONCLUSIONS: Findings suggest that in private managed care populations, particular behavioral indicators may be more important than demographic characteristics in screening for problem drinkers. The identification of individuals who report a mental health symptom, who drink a large number of drinks occasionally or who report any drug use may be important in a health maintenance approach to prevention and case finding.

Adolescent↗

Herbal vitamins: lead toxicity and developmental delay.

A case of lead poisoning from an Indian herbal vitamin is presented. The patient who was developmentally delayed was given an herbal vitamin from India to strengthen his brain. The tablet contained large amounts of lead and mercury, leading to significant lead burden. Vulnerability of families and lack of awareness of health care professionals of dangers of unknown herbal supplementation are discussed.

Child, Preschool↗

A comparative study of the effects of two oral contraceptives containing dienogest or desogestrel on the human immune system.

The effects of two oral contraceptive combinations, dienogest 2.0 mg plus ethinyl estradiol 0.03 mg (Valette) and desogestrel 0.15 mg plus ethinyl estradiol 0.02 mg (Lovelle), on the human immune system were compared over one treatment cycle of 31 patients (n = 15 and n = 16, respectively). Lovelle but not Valette significantly increased the numbers of lymphocytes, monocytes and granulocytes. Valette decreased CD4 lymphocytes after 10 days' treatment; Lovelle had the opposite effect. Lovelle increased CD19 and CD23 after 21 days' treatment. Phagocytic activity was unaffected by either treatment. After 10 days' treatment, both contraceptives reduced serum IgA, IgG and IgM, which remained lowered at day 21 with Lovelle but returned to baseline with Valette. Secretory IgA was unaffected by either contraceptive. Neither treatment affected levels of interleukins, except for a significant difference between the treatment groups for interleukin-6 after 10 days' treatment that disappeared after 21 days' treatment. Levels of non-immunoglobulin serum components fluctuated; macroglobulin was increased with Valette. However, total protein and albumin levels were reduced more with Lovelle than with Valette. Complement factors also fluctuated. There was no evidence for any sustained immunosuppression with either Valette or Lovelle.

Adolescent↗

The outcome and cost of alcohol and drug treatment in an HMO: day hospital versus traditional outpatient regimens.

OBJECTIVE: To compare outcome and cost-effectiveness of the two primary addiction treatment options, day hospitals (DH) and traditional outpatient programs (OP) in a managed care organization, in a population large enough to examine patient subgroups. DATA SOURCES: Interviews with new admissions to a large HMO's chemical dependency program in Sacramento, California between April 1994 and April 1996, with follow-up interviews eight months later. Computerized utilization and cost data were collected from 1993 to 1997. STUDY DESIGN: Design was a randomized control trial of adult patients entering the HMO's alcohol and drug treatment program (N = 668). To examine the generalizability of findings as well as self-selection factors, we also studied patients presenting during the same period who were unable or unwilling to be randomized (N = 405). Baseline interviews characterized type of substance use, addiction severity, psychiatric status, and motivation. Follow-up interviews were conducted at eight months following intake. Breathanalysis and urinalysis were conducted. Program costs were calculated. DATA COLLECTION: Interview data were merged with computerized utilization and cost data. PRINCIPAL FINDINGS: Among randomized subjects, both study arms showed significant improvement in all drug and alcohol measures. There were no differences overall in outcomes between DH and OP, but DH subjects with midlevel psychiatric severity had significantly better outcomes, particularly in regard to alcohol abstinence (OR = 2.4; 95% CI = 1.2, 4.9). The average treatment costs were $1,640 and $895 for DH and OP programs, respectively. In the midlevel psychiatric severity group, the cost of obtaining an additional person abstinent from alcohol in the DH cohort was approximately $5,464. Among the 405 self-selected subjects, DH was related to abstinence (OR = 2.1; 95% CI = 1.3, 3.5). CONCLUSIONS: Although significant benefits of the DH program were not found in the randomized study, DH treatment was associated with better outcomes in the self-selected group. However, for subjects with mid-level psychiatric severity in both the randomized and self-selected samples, the DH program produced higher rates of abstention and was more cost-effective. Self-selection in studies that randomize patients to services requiring very different levels of commitment may be important in interpreting findings for clinical practice.

Adult↗

Health visitors' knowledge and attitudes relating to HIV and AIDS.

Infection with human immunodeficiency virus (HIV) is increasing in the heterosexual community and people already affected by HIV are living longer. As a result, health visitors will be more involved in caring for people with HIV and acquired immune deficiency syndrome (AIDS). The aim of this study was to assess the knowledge level of health visitors about HIV infection and AIDS, and to identify some of the attitudes held by them concerning AIDS and the variety of symptoms that can occur in HIV positive individuals (AIDS related complex) before they have actually developed AIDS. The influence of AIDS-related education and the experience of caring for affected patients on health visitors' knowledge of the disease was assessed. The attitudes of carers towards these patients were also ascertained. All heath visitors (n = 88) working in the Merton and Sutton Community Healthcare Trust were invited to participate in a questionnaire survey. Fifty-five health visitors participated. Knowledge relating to HIV and AIDS was good, but the majority of respondents felt they did not have all the information they needed about HIV and AIDS. Almost one-quarter of respondents had cared for a client who was either HIV positive or had AIDS. Overall, the findings were quite encouraging. However, further education, training, and support were identified as necessary. These shortfalls need to be addressed in order to fully assist health visitors in their role of caring for clients and families affected by HIV and AIDS.

Acquired Immunodeficiency Syndrome↗

Relationship between the conserved alpha subunit arginine 107 and effects of phosphate on the activity and stability of Vibrio harveyi luciferase.

The Arg107 of the alpha subunit is a conserved residue for all known bacterial luciferases. The phosphate moiety of the reduced flavin mononucleotide (FMNH(2)) side chain has been hypothesized to be anchored at this site (A. J. Fisher, F. M. Raushel, T. O. Baldwin, and I. Rayment Biochemistry 34, 6581-6586, 1995). Mutations of alphaArg107 of the Vibrio harveyi luciferase to alanine, serine, and glutamate were carried out to test such a hypothesis. These variants were characterized and compared with the wild-type luciferase with respect to their K(m) for decanal, FMNH(2), and reduced riboflavin in both low- (0.01 or 0.05 M) and high- (0.3 M) phosphate buffers at pH 7.0. Results are consistent with the hypothesized binding of the FMNH(2) phosphate group by alphaArg107. Moreover, the alphaArg107 residue was apparently important in the expression of the luciferase maximal activity and aldehyde binding. Phosphate ion is also known to have other effects on luciferase stability. We compared the three luciferase variants with the native enzyme with respect to the decay rate of the FMN 4a-hydroperoxide intermediate II, and rates of inactivation by trypsin digestion, modification by N-ethylmaleimide, and heat treatment in low- and high-phosphate buffers. On the basis of patterns of the phosphate effects, alphaArg107 appeared to be important to the enhancement of luciferase stability against trypsin proteolysis at high phosphate but was not involved in regulating the intermediate II decay or sensitivity to N-ethylmaleimide modification. Differential effects of mutations on luciferase thermal stability were observed. It is uncertain whether alphaArg107 is involved in the enhanced thermal stability of the native luciferase in high phosphate buffer.

Alanine↗

Active immunoneutralization of somatostatin in the sheep: effects on gastrointestinal somatostatin expression, storage and secretion.

In the absence of somatostatin antagonists, somatostatin antisera administered acutely or animals chronically immunized against somatostatin have been used to define the functions of somatostatin. However, the circulating immunoglobulins from immunized animals may contain substantial quantities of endogenous hormones. This has not been examined for somatostatin. We have measured the amount of free somatostatin bound to circulating immunoglobulins in somatostatin-immunized animals and the effect of this sequestering of the free peptide on somatostatin secretion and gastric somatostatin synthesis and storage. The average concentration of somatostatin bound to the antisera was 6.9 nmol/l, about 1000-fold higher than normal circulating levels. Compared to control animals, there was a doubling of somatostatin mRNA in the fundus and a 4-fold increase in fundic somatostatin peptide. Similar increases were seen in pancreas, but the antrum was not significantly affected providing further evidence of distinct regulatory mechanisms between the antrum and fundus. We suggest that withdrawal of active somatostatin activates a regulatory loop to increase fundic somatostatin biosynthesis and storage. The data support the concept that somatostatin autoregulates its own expression at both the RNA and peptide level.

Animals↗

The detection of cotinine in hydrolyzed meconium samples.

To date, the screening of meconium for the determination of tobacco exposure in newborns has proven difficult. It was hypothesized that cotinine forms reversible Schiff base bonds with free amino functions on proteins, therefore, hydrolysis of meconium would be necessary for the detection of 'free' cotinine. One-hundred-and-two (102) meconium samples received into our laboratory were extracted using a routine non-hydrolysis screening procedure for drugs of abuse. Separate aliquots of the specimens were hydrolyzed and re-extracted according to the same procedure. The results of the two methods were compared using a highly specific cotinine micro-plate enzyme immunoassay procedure (EIA). Of the non-hydrolyzed samples, 33% were positive for cotinine, while 79% of the hydrolyzed samples were cotinine-positive. Common drugs of abuse did not interfere with the analysis. Micro-plate EIA provides a rapid, simple and reliable screening method for the determination of cotinine in meconium following hydrolysis and extraction. In general, the meconium specimens received into our laboratory are from newborns considered to be at risk for post-natal problems due to suspected drug and/or alcohol abuse during pregnancy.

Cotinine↗

Mental health. Open and shut case.

Acute mental care consumes about two-thirds of all mental health spending. But many beds are blocked by patients who no longer need intensive support. They stay in hospital because of a lack of alternative services. If each patient left hospital when they were deemed ready, inpatient costs would be almost halved. More than a third of these patients are re-admissions. A range of alternative crisis services, including 24-hour nursing care and staffed hostels, are needed.

Bed Occupancy↗

Constitutively active MuSK is clustered in the absence of agrin and induces ectopic postsynaptic-like membranes in skeletal muscle fibers.

In skeletal muscle fibers, neural agrin can direct the accumulation of acetylcholine receptors (AChR) and transcription of AChR subunit genes from the subsynaptic nuclei. Although the receptor tyrosine kinase MuSK is required for AChR clustering, it is less clear whether MuSK regulates gene transcription. To elucidate the role of MuSK in these processes, we constructed a constitutively active MuSK receptor, MuSKneuTMuSK, taking advantage of the spontaneous homodimerization of the transmembrane domain of neuT, an oncogenic variant of the neu/erbB2 receptor. In the extrasynaptic region of innervated muscle fibers, MuSKneuTMuSK formed highly concentrated aggregates that colocalized with AChR clusters. Associated with MuSK-induced AChR clusters was a normal complement of synaptic proteins. Moreover, transcription of the AChR-epsilon subunit gene was increased, albeit via an indirect mechanism by MuSK-induced aggregation of erbB receptors and neuregulin. Although neural agrin was not required, the activity of MuSKneuTMuSK was nevertheless potentiated by ectopic expression of a muscle agrin isoform inactive in AChR clustering. To define the role of the kinase domain in the formation of a postsynaptic-like membrane, a second fusion receptor, neuneuTMuSK, which included the MuSK kinase but not the MuSK extracellular domain, was expressed. Significantly, neuneuTMuSK induced AChR clusters that colocalized with aggregates of endogenous MuSK. Taken together, it was concluded that the MuSK kinase domain is sufficient to initiate the recruitment of additional MuSK receptors, which then develop into highly concentrated aggregates by means of a positive feedback loop to induce a postsynaptic membrane in the absence of neural agrin.

Agrin↗