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Biomedical subjects

P Anderson

Publications and source records attributed to P Anderson.

At least 199 records · Page 11Linked to original sources
PubMed1996

Individual RNA recognition motifs of TIA-1 and TIAR have different RNA binding specificities.

TIA-1 and TIAR are two closely related RNA recognition motif (RRM) proteins which possess three RRM-type RNA binding domains (RRMs 1, 2, and 3). Although both proteins have been implicated as effectors of apoptotic cell death, the specific functions of TIA-1 and TIAR are not known. We have performed in vitro selection/amplification from pools of random RNA sequences to identify RNAs to which TIA-1 and TIAR bind with high affinity. Both proteins selected RNAs containing one or several short stretches of uridylate residues suggesting that the two proteins have similar RNA binding specificities. Replacement of the uridylate stretch with an equal number of cytidine residues eliminates the protein-RNA interaction. Mutational analysis indicates that, for both TIA-1 and TIAR, it is the second RNA binding domain (RRM 2) which mediates the specific binding to uridylate-rich RNAs. Although RRM 2 is both necessary and sufficient for this interaction, the affinity for the selected RNA (as determined by filter binding assays) does increase when the second domain of TIAR is expressed together with the first and third domains (Kd = 2 x 10(-8) M) rather than alone (Kd = 5 x 10(-8) M). Although RRM 3 (of either TIA-1 or TIAR) does not interact with the uridylate-rich sequences selected by the full-length proteins, it is a bona fide RNA binding domain capable of affinity-precipitating a population of cellular RNAs ranging in size from 0.5 to 5 kilobases. In contrast, RRM 1 does not affinity-precipitate cellular RNA. The inability of RRM 1 to interact with RNA may be due to the presence of negatively charged amino acids within the RNP 1 octamer.

Base Sequence↗
PubMed1996

Characterization of GMP-17, a granule membrane protein that moves to the plasma membrane of natural killer cells following target cell recognition.

Cytotoxic lymphocytes are characterized by their inclusion of cytoplasmic granules that fuse with the plasma membrane following target cell recognition. We previously identified a cytotoxic granule membrane protein designated p15-TIA-1 that is immunochemically related to an RNA-recognition motif (RRM)-type RNA-binding protein designated p40-TIA-1. Although it was suggested that p15-TIA-1 might be derived from p40-T1A-1 by proteolysis, N-terminal amino acid sequencing of p15-TIA-1 immunoaffinity purified from a natural killer (NK) cell line by using monoclonal antibody (mAb) 2G9 revealed that p15-T1A-1 is identical to the deduced amino acid sequence of NKG7 and GIG-1, cDNAs isolated from NK cells and granulocyte-colony-stimulating factor-treated mononuclear cells, respectively. Epitope mapping revealed that mAb 2G9 recognizes the C terminus of p15-T1A-1 and p40-T1A-1. The deduced amino acid sequence of p15-T1A-1/NKG7/GIG-1 predicts that the protein possesses four transmembrane domains, and immuno-electron microscopy localizes the endogenous protein to the membranes of cytotoxic granules in NK cells. Given its subcellular localization, we propose to rename-this protein GMP-17, for granule membrane protein of 17 kDa. Immunofluorescence microscopy of freshly isolated NK cells confirms this granular localization. Target cell-induced NK cell degranulation results in translocation of GMP-17 from granules to the plasma membrane, suggesting a possible role for GMP-17 in regulating the effector function of lymphocytes and neutrophils.

Amino Acid Sequence↗
PubMed1996

Hydrogen peroxide secreted by tumor-derived macrophages down-modulates signal-transducing zeta molecules and inhibits tumor-specific T cell-and natural killer cell-mediated cytotoxicity.

Although alterations in CD3-associated signal-transducing molecules in tumor-infiltrating T cells of patients with advanced cancer have been previously described, the mechanism behind these changes is not known. We demonstrate that macrophages isolated from metastatic lymph nodes of patients with malignant melanoma down-regulate levels of CD3 zeta in autologous peripheral blood T cells. Lipopolysaccharide (LPS)- or phorbol 12-myristate 13-acetate (PMA)-stimulated monocytes derived from peripheral blood of healthy donors also induced decreased expression of CD3 and CD16-associated zeta chains similar to that observed in T cells and natural killer (NK) cells of patients with advanced cancer. Co-culture with activated monocytes impaired Ca2+ mobilization in peripheral blood derived-T cells when stimulated with monoclonal antibodies to CD3 and also strongly inhibited melanoma-specific cytotoxic T lymphocyte (CTL) activity and NK activity. The presence of catalase, a scavenger of H2O2, during co-culture almost totally abrogated the inhibitory effect of activated monocytes on melanoma-specific CTL lines and on NK cells. Pre-treatment of CTL or NK cells with nontoxic concentrations (1 x 10(-5) M) of H2O2 also severely reduced their cytotoxic activity which could be prevented by catalase. The decrease in CD3 zeta and in CD16 zeta expression, induced by macrophages isolated from metastatic lymph nodes or by LPS-stimulated monocytes, was also prevented by catalase when maintained throughout the co-culture period. The possibility that monocyte/macrophage-derived reactive oxygen metabolites contribute directly to alterations in signal transducing molecules of T cells and NK cells and to the mechanism of immunosuppression in individuals with cancer should be considered.

CD3 Complex↗
PubMed1996

Relaxation kinetics of formoterol and salmeterol in the guinea pig trachea in vitro.

The mechanisms producing long duration of action for formoterol and salmeterol are not fully understood. The aim of the current study was to examine how the concentration of long and short acting beta 2-adrenoceptor agonists affects their relaxation kinetics in airway smooth muscle. Onset (time to peak relaxation) and offset of action (reassertion of reversible relaxation followed repeated beta-adrenoceptor blockade and washout) were measured in the guinea pig trachea precontracted postjunctionally by carbachol 0.3 microM in vitro. At 10-1,000% (C10-C1,000) of the maximally effective concentration (C100: 150 nM formoterol, 10 microM salbutamol, 30 microM salmeterol), salbutamol had a shorter time to peak relaxation than did salmeterol. Formoterol and salmeterol had a similar time to peak relaxation at C10, but, in contrast to salmeterol, formoterol's time to peak relaxation became markedly shorter and similar to that of salbutamol as the concentration was increased up to C1,000. Significant reversible reasserted relaxation was demonstrated for salmeterol alone at C10. At C30-C1,000, however, salmeterol produced irreversible relaxation only, in spite of repeated beta-adrenoceptor blockade by sotalol 10 microM followed by washout. In contrast, formoterol produced an increasing reversible reasserted relaxation at C30-C1,000. Salbutamol produced significant, reversible reasserted relaxation at C1,000 only. In conclusion, the concentration determines the onset and offset of action for formoterol and to a lesser extent for salbutamol, but not for salmeterol. To cause sustained action, a submaximally effective concentration is sufficient for salmeterol, whereas formoterol requires a maximally effective concentration. The rank order of concentration dependence for the relaxation kinetics is not paralleled by the rank order of lipophilicity for formoterol, salbutamol, and salmeterol. Therefore, factors other than lipophilicity may also play a role in determining the relationship between concentration and relaxation kinetics for the investigated beta 2-agonists.

Adrenergic beta-Agonists↗
PubMed1996

A comparison of the mineral content of enamel and dentine in human premolars and enamel pearls measured by X-ray microtomography.

Mineral content gradients in two composite enamel pearls from permanent human upper molars were measured by X-ray microtomography (XMT) at a resolution of 15-30 microns. This non-destructive microscopic technique was used to make 15-microns thick XMT slices with 100-microns separation through one pearl and 250-microns separation through the other. Average mineral contents were calculated from the linear absorption coefficients determined from regions of the XMT slices assuming the inorganic component to be calcium hydroxyapatite. These values were compared with similar XMT studies of coronal enamel and dentine of upper permanent premolars. A mineral content gradient in the pearls, reducing from the enamel surface to the amelodentinal junction, was found; this was similar to that observed in the coronal enamel of the upper premolar. The mineral contents in the surface and deeper enamel regions of the pearl were similar to those observed in premolar enamel. In contrast, the mineral content for the dentine of the pearl was greatest at the amelodentinal junction, i.e. the gradient was in the opposite direction to that observed in premolar dentine. These results suggest that the process of mineralization of the pearl dentine differs from that in permanent control dentine. In addition, gradients in enamel and dentine mineral contents reducing from the tip of the pearl to the base of the pearl were found.

Bicuspid↗
PubMed1996

WHO working group on population levels of alcohol consumption: Oslo, 14-16 December 1994.

Target 17 of the Health Policy for Europe calls for the health-damaging consumption of dependence-producing substances such as alcohol, tobacco and psychoactive substances to be significantly reduced in all Member States between the year 1980 and the year 2000. With regard to alcohol, it is suggested that alcohol consumption be reduced by 25%, with particular attention to reducing harmful use. A question posed by a number of Member States is what is the level of per capita alcohol consumption of lowest risk to physical, psychological and social harm. A working group was convened to consider population levels of alcohol consumption with particular reference to the Member States of the European Region of WHO. A basis for understanding population problem experience can be established through the interaction between individual risk and distribution of consumption levels within the population. The working group concluded that public health policy within the European Region should continue to advise decreases of per capita consumption. Even when taking into account coronary heart disease, it can be concluded at the population level, across all ranges of alcohol consumption found in almost all countries of Europe, that a reduction in consumption is linked to better health. However, public health policy concerning alcohol should not be based solely on mortality. All outcomes of drinking, that is mortality, morbidity, social and criminal consequences, as well as quality of life, should be considered. The existing data relating alcohol consumption to health originates from countries primarily with a cultural experience of consuming alcohol. In those countries, where there is a cultural or religious tradition of not consuming alcohol, there can be no public health grounds for recommending alcohol consumption.

Adult↗
PubMed1996

unc-68 encodes a ryanodine receptor involved in regulating C. elegans body-wall muscle contraction.

Striated muscle contraction is elicited by the release of stored calcium ions through ryanodine receptor channels in the sarcoplasmic reticulum. ryr-1 is a C. elegans ryanodine receptor homologue that is expressed in body-wall muscle cells used for locomotion. Using genetic methods, we show that ryr-1 is the previously identified locus unc-68. First, transposon-induced deletions within ryr-1 are alleles of unc-68. Second, transformation of unc-68 mutants with ryr-1 genomic DNA results in rescue of the Unc phenotype. unc-68 mutants move poorly, exhibiting an incomplete flaccid paralysis, yet have normal muscle ultrastructure. The mutants are insensitive to the paralytic effects of ryanodine, and lack detectable ryanodine-binding activity. The Unc-68 phenotype suggests that ryanodine receptors are not essential for excitation-contraction coupling in nematodes, but act to amplify a (calcium) signal that is sufficient for contraction.

Animals↗
PubMed1996

Psychosocial and family functioning in children with insulin-dependent diabetes at diagnosis and one year later.

Examined the initial impact and subsequent adjustment to the diagnosis of insulin-dependent diabetes mellitus (IDDM). Children between 1 and 14 years of age and their families were assessed several weeks after diagnosis and again a year later using standardized measures of child behavior, parental mental health, and family functioning. Immediately after diagnosis, the children and both parents exhibited mild symptoms of psychological distress but these had largely resolved at 12-month follow-up. The impact of IDDM diagnosis on family functioning varied with informant, SES, and the age of the child, with an overall tendency for families to become less flexible over the year. Findings suggest that most children and their parents exhibit satisfactory individual adjustment after a period of initial stress but family functioning is affected in complex ways. Serial follow-up of the cohort is planned to establish whether the current findings are predictive of longer term outcome.

Adaptation, Psychological↗
PubMed1996

An evaluation of the copper-bromide laser for treating telangiectasia.

BACKGROUND: Copper bromide lasers, producing pulsed yellow and green light, have been developed for treating cutaneous lesions. OBJECTIVE: A clinical trial was conducted to evaluate the role of this laser, using its yellow wavelength, to treat benign vascular ectasia and establish some clinical guidelines for therapy. METHODS: Twenty-three informed consenting adults with facial telangiectasia, spider angiomas, or vascular nevi on the head, neck, or upper chest were treated with the laser. Assessment of results was performed by: blinded clinical evaluation, blinded comparison of "before" and "after" photographs, and patients' own reports of satisfaction levels. RESULTS: Good to excellent results were obtained in most patients, except for a few suffering minor skin atrophy where very large vessels were treated. CONCLUSIONS: The copper bromide laser was an effective tool in the treatment of certain cutaneous vascular lesions.

Adult↗
PubMed1996

Interlaboratory study evaluating quantitation of antibodies to Haemophilus influenzae type b polysaccharide by enzyme-linked immunosorbent assay.

An interlaboratory study was conducted to determine whether an enzyme-linked immunosorbent assay (ELISA) with an antigen preparation composed of various-sized fragments of Haemophilus influenzae type b polysaccharide conjugated to human serum albumin could be standardized across laboratories and whether the ELISA-derived results from different laboratories are equivalent to those obtained by the standard radioactive antigen binding assay (RABA) for quantitation of anti-H, influenzae type b polysaccharide antibodies. Twenty coded human serum samples were quantitated by ELISA in 11 laboratories and by RABA in 5 laboratories. The mean RABA-derived values served as the basis for all comparisons. While the overall correspondence of antibody values between the two methods was good, significant differences were found among some of the 11 ELISA data sets and among the mean RABA values. Seven laboratories generated higher ELISA antibody values for low-titered sera. Four laboratories generated antibody concentrations that were not statistically different between the two assay methods. The results therefore indicate that the ELISA can tolerate substantial variations in protocol, such as the use of different plates and different antibody reagents, without affecting the quantitation of serum antibodies. However, attention should be focused on low-titered sera, as some assay conditions may yield spurious results. This ELISA is a serologic assay which can serve as an alternative to the RABA for quantitation of antibodies to H. influenzae type h polysaccharide.

Adult↗
PubMed1996

Splicing removes the Caenorhabditis elegans transposon Tc1 from most mutant pre-mRNAs.

The transposable element Tc1 is responsible for most spontaneous mutations that occur in many Caenorhabditis elegans strains. We analyzed the abundance and sequence of mRNAs expressed from five different Tc1 insertions within either hlh-1 (a MyoD homolog) or unc-54 (a myosin heavy chain gene). Each of the mutants expresses substantial quantities of mature mRNA in which most or all of Tc1 has been removed by splicing. Such mRNAs contain small insertions of Tc1 sequences and/or deletions of target gene sequences at the resulting spliced junctions. Most of these mutant mRNAs do not contain premature stop codons, and many are translated in frame to produce proteins that are functional in vivo. The number and variety of splice sites used to remove Tc1 from these mutant pre-mRNAs are remarkable. Two-thirds of the Tc1-containing introns removed from hlh-1 and unc-54 lack either the 5'-GU or AG-3' dinucleotides typically found at the termini of eukaryotic introns. We conclude that splicing to remove Tc1 from mutant pre-mRNAs allows many Tc1 insertions to be phenotypically silent. Such mRNA processing may help Tc1 escape negative selection.

Alleles↗
PubMed1996

Monitoring de- and remineralisation of enamel in vitro using an infrared reflectance meter.

The aim of this study was to design and investigate the use of an inexpensive method of monitoring the progress of demineralisation and subsequent remineralisation in artificial carious lesions. A small infrared (IR) reflectance meter was built which illuminated a 4 mm x 4 mm area on the buccal surface of a tooth and measured the reflected IR intensity. Repeated measurements were taken over a period of 25 days, during which the enamel surface was exposed to demineralising and subsequently remineralising solutions. Thirty-six teeth were studied under a variety of de- and remineralising conditions. It was observed that the IR specular reflectance of the tooth surfaces decreased with time during lesion formation and increased with time during remineralisation. It is suggested that the decrease in IR specular reflectance during demineralisation and the increase during remineralisation are a result of continuous changes in the crystals at the enamel surface during these processes.

Dental Caries Activity Tests↗
PubMed1996

The potential role of amifostine in conjunction with cisplatin in the treatment of locally advanced carcinoma of the cervix.

The treatment of locally advanced carcinoma of the cervix with radiation therapy as a single modality is inadequate, specifically for stage III and IVA disease. While chemotherapy as single-modality therapy is ineffective in advanced cervical cancer, there is some evidence of efficacy when used in combination with radiation therapy. A recently conducted phase II trial from the Albert Einstein College of Medicine used standard whole pelvic radiation therapy with concurrent cisplatin 20 mg/m(2)/d X 5 days for four courses in women with stage IB to IVA cervical cancer. Toxicities, mainly hematologic and soft tissue, were acceptable in this trial. There was only a modest impact on disease-free survival among women with stage III disease. A subsequent phase I trial conducted by the New York Gynecologic Oncology Group tested the addition of amifostine to the combination of cisplatin plus radiation therapy using the Albert Einstein College of Medicine regimen. Amifostine at doses escalated from 340 to 910 mg/m(2) was administered immediately before cisplatin. The dose-limiting toxicity was hypotension. Amifostine should be tested in future clinical trials either as a cytoprotective agent in patients receiving cisplatin plus radiation therapy or, alternatively, to assess dose intensification of cisplatin in combination with radiation therapy.

Amifostine↗
PubMed1996

Heart rate response during handball singles match-play and selected physical fitness components of experienced male handball players.

Limited information is available concerning the exercise response during handball (HB) singles match-play. Also, few studies exist that have examined VO2 peak and body composition of HB players. The purpose of this study was to examine the heart rate (HR) response during match play and peak physiologic responses and relative fat in twelve experienced HB players. Peak physiologic responses were measured during treadmill running and body composition was assessed via hydrodensiotometry. During HB match-play, HR was measured and stored every five seconds using a Polar Vantage XL heart watch. Physical characteristics and peak physiologic responses included the following: Age (yrs) 47.2; BW (kg) 78.0; height (cm) 178.9; % fat 18.9; VO2 peak (ml.kg-1.min-1) 48.0; RER peak 1.03; HR peak (bpm) 183.1 and lactic acid peak (mmol.l-1) 10.3. During HB match-play, HR averaged 85% of peak during one hour of play. Moreover, 67% of match-play time, HR was > 80% of peak. When HR responses were examined over one hour of match-play (twelve, five minute blocks) only the first five minutes were significantly different (lower) than the other 55 minutes. The exercise intensity and the relatively stable HR response observed during HB suggests that this activity appears to be appropriate for meeting the American College of Sports Medicine guidelines to develop and maintain cardiorespiratory fitness.

Adult↗