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At least 919 records · Page 51Linked to original sources
PubMed2006

Randomized phase II three-arm trial with three platinum-based doublets in metastatic non-small-cell lung cancer. An Italian Trials in Medical Oncology study.

BACKGROUND: Many patients with advanced non-small-cell lung cancer (NSCLC) do not tolerate cisplatin-based regimens because of its nonhemathological toxicity. PATIENTS AND METHODS: We evaluated the response rate safety of new platinum analogue regimens, randomizing 147 patients with nonoperable IIIB/IV NSCLC to (i) carboplatin (area under the curve = 5 mg min/ml) on day 1 plus gemcitabine (GEM) (1000 mg/m(2)) on days 1 and 8 for six cycles; (ii) same regimen for three cycles followed by docetaxel (Taxotere) (40 mg/m(2)) on days 1 and 8 plus GEM (1250 mg/m(2)) on days 1 and 8 for three cycles; (iii) oxaliplatin (130 mg/m(2)) on day 1 plus GEM (1250 mg/m(2)) on days 1 and 8 for six cycles. RESULTS: Intention-to-treat objective response rates were 25%, 25% and 30.6% in arms A, B and C, respectively. Median survival was 11.9, 9.2 and 11.3 months in arms A, B and C, respectively. Grade 3/4 neutropenia/anemia occurred in 29%/12.5%, 10%/16.5% and 8%/6% of arms A, B and C, respectively; grade 3/4 thrombocytopenia in 20.5%, 16.5% and 6%; grade 1/2 neurological toxicity in 43% of arm C. CONCLUSIONS: Oxaliplatin/GEM (arm C) had similar activity to carboplatin/GEM (arm A), but milder hematological toxicity and may be worth testing in a phase III study against carboplatin/GEM in patients not suitable for cisplatin. The sequential regimen gave no additional benefit.

Adult↗
PubMed1999

Mytilus mitochondrial DNA contains a functional gene for a tRNASer(UCN) with a dihydrouridine arm-replacement loop and a pseudo-tRNASer(UCN) gene.

A 2500-nucleotide pair (ntp) sequence of F-type mitochondrial (mt) DNA of the Pacific Rim mussel Mytilus californianus (class Bivalvia, phylum Mollusca) that contains two complete (ND2 and ND3) and two partial (COI and COIII) protein genes and nine tRNA genes is presented. Seven of the encoded tRNAs (Ala, Arg, His, Met(AUA), Pro, Ser(UCN), and Trp) have the potential to fold into the orthodox four-armed tRNA secondary structure, while two [tRNASer(AGN) and a second tRNASer(UCN)] will fold only into tRNAs with a dihydrouridine (DHU) arm-replacement loop. Comparison of these mt-tRNA gene sequences with previously published, corresponding M. edulis F-type mtDNA indicates that similarity between the four-armed tRNASer(UCN) genes is only 63.8% compared with an average of 92.1% (range 86.2-98. 5%) for the remaining eight tRNA genes. Northern blot analysis indicated that mature tRNAs encoded by the DHU arm-replacement loop-containing tRNASer(UCN), tRNASer(AGN), tRNAMet(AUA), tRNATrp, and tRNAPro genes occur in M. californianus mitochondria, strengthening the view that all of these genes are functional. However, Northern blot and 5' RACE (rapid amplification of cDNA ends) analyses indicated that the four-armed tRNASer(UCN) gene is transcribed into a stable RNA that includes the downstream COI sequence and is not processed into a mature tRNA. On the basis of these observations the M. californianus and M. edulis four-armed tRNASer(UCN) sequences are interpreted as pseudo-tRNASer(UCN) genes.

Amino Acid Sequence↗
PubMed1991

Direct haplotype determination by double ARMS: specificity, sensitivity and genetic applications.

We have developed a novel double Amplification Refractory Mutation System (double ARMS) using a highly polymorphic region 5' to the human delta-globin gene as a model system. The double ARMS approach involves using two allele-specific ARMS primers simultaneously during DNA amplification by the polymerase chain reaction (PCR). The resulting system is highly sensitive and more specific than single ARMS. In addition, this approach enables the elucidation of the relationship of polymorphic sites on the same chromosome and thus allows the direct determination of haplotypes. We have also demonstrated that this system can be used in conjunction with inverse PCR, the resulting double ARMS inverse PCR (DARMSI-PCR) may allow haplotype determination on polymorphic sites which are separated further apart than the length limit imposed by PCR. The double ARMS approach has numerous other applications in molecular biology including HLA typing, virology, forensic pathology and the investigation of the phenomenon of chimerism following bone marrow transplantation.

Alleles↗
PubMed2003

Long-distance radical cation reactions in DNA three-way junctions: inter-arm interaction and migration through the junction.

DNA three-way junctions (TWJ) are branched molecules having three 'arms'. We studied long-distance radical cation migration in these assemblies by incorporating anthraquinone (AQ) groups linked by a covalent tether to one strand of one arm of the TWJ. Excitation of the AQ at 350 nm results in one-electron oxidation of the DNA, which generates a base radical cation. This leads to relatively inefficient (compared with duplex DNA) strand cleavage at guanines following piperidine treatment of the irradiated samples. When the AQ is linked to the 5'-terminus of arm III by a flexible tether, gel electrophoretic analysis shows that strand cleavage occurs at the guanines in all three arms. We also investigated a TWJ in which the anthraquinone is specifically intercalated in arm III. In this case, a different pattern of strand cleavage is detected. We conclude that there are at least two mechanisms for long-distance radical cation migration in TWJs: (i) by inefficient charge hopping through the junction; (ii) by a through-space, cross-arm interaction when the AQ is on a flexible tether.

Anthraquinones↗
PubMed1988

Angina and ST-segment depression during treadmill and arm ergometer testing in patients with coronary artery disease.

The clinical use of exercise rehabilitation programs has increased for patients with coronary artery disease. Exercise testing in these programs typically is conducted on a treadmill or cycle ergometer, although many patients' vocations require upper extremity activities and some patients cannot perform lower extremity exercises. To compare the hemodynamic responses and the incidence of angina and ST-segment depression during upper and lower extremity exercise in patients with coronary artery disease, we administered symptom-limited arm ergometer and submaximal or maximal symptom-limited treadmill tests to 95 cardiac rehabilitation patients who had completed an eight-week exercise training program. Treadmill testing resulted in significantly higher heart rates, systolic blood pressures, and double products than arm ergometer testing. The incidence of ST-segment depression was significantly greater with treadmill testing than with arm ergometer testing, but the incidence of angina was not different between tests. Ten patients had ST-segment depression during both arm ergometer and treadmill testing, and the double products at the onset of ST-segment depression were not different. Our data suggest that arm ergometer testing is less likely to result in ST-segment depression than treadmill testing in patients with coronary artery disease, possibly because of the lower hemodynamic responses during arm ergometer testing.

Coronary Disease↗
PubMed1992

The medial arm flap.

The reports of transfer of the medial arm flap have been inconsistent, and confusion remains about its anatomy and use. In 40 fresh cadaver arms, the vascular supply to the medial side of the arm was studied after latex injection. The superior ulnar collateral artery was present in 39 of 40 dissections and was the most consistent prominent blood supply to this area. In 57.5% of dissections, direct cutaneous arteries > 1.0 mm were present, and in 47.5%, multiple muscular cutaneous arteries > 1.0 mm were present. Although the blood supply to the medial arm flap is multiple, at least one pedicle > 1.0 mm can be found in all dissections. To date, 10 consecutive medial arm flaps were used to cover upper and lower extremity defects without any flap loss. With knowledge of the anatomical variations, the medial arm flap is a plausible reconstructive option.

Adult↗
PubMed2001

Effects of physical training of the dominant arm on ipsilateral radial artery distensibility and structure.

BACKGROUND: Exercise training induces cardiovascular changes that are both generalized and restricted to the microcirculation of the tissues more actively involved in the exercise itself. Whether the local effect of exercise extends to larger arteries is unknown, however. METHODS: In the right and left upper limb of 17 right-handed subjects performing an asymmetric training of the upper limbs (hammer throwers and baseball players) and 16 age-matched sedentary controls, we continuously measured radial artery diameter, distensibility and wall thickness by an echotracking and a beat-to-beat finger blood pressure device. Arterial distensibility was calculated by the arctangent model of Langewouters and expressed as continuous values from diastolic to systolic blood pressure. Measurements were made: (1) in baseline conditions; (2) after release from prolonged proximal ischaemia; and (3) after an increase in radial artery blood flow caused by a short (4 min) distal ischaemia to determine the endothelial involvement in the training-induced change in arterial distensibility. RESULTS: In athletes the radial artery distensibility was markedly greater in the right than in the left arm, the latter showing values slightly greater than those seen in the two arms of sedentary subjects. In both arms and groups radial artery distensibility increased markedly after prolonged ischaemia, the between arm and group differences being preserved, however. The radial artery response to distal short ischaemia was, on the other hand, similar in the two arms of the athletes, although greater in these subjects than in the sedentary ones. Radial artery wall thickness was greater in the trained than in the untrained arm of athletes, both values being greater than in sedentary subjects. CONCLUSIONS: Asymmetrical training of the upper limbs is accompanied by a greater distensibility of the middle-sized arteries of the more trained side. This is not associated with asymmetrical changes in endothelial structure or function. It is associated with a greater wall thickness in the trained side, suggesting that, at least in part, a training-induced asymmetrical change in wall structure (possibly with a predominance of more distensible tissues such as elastine and smooth muscle) is responsible.

Adolescent↗
PubMed1998

Influence of muscle morphometry and moment arms on the moment-generating capacity of human neck muscles.

STUDY DESIGN: The function of neck muscles was quantified by incorporating experimentally measured morphometric parameters into a three-dimensional biomechanical model. OBJECTIVE: To analyze how muscle morphometry and moment arms influence moment-generating capacity of human neck muscles in physiologic ranges of motion. SUMMARY OF BACKGROUND DATA: Previous biomechanical analyses of the head-neck system have used simplified representations of the musculoskeletal anatomy. The force- and moment-generating properties of individual neck muscles have not been reported. METHODS: A computer graphics model was developed that incorporates detailed neck muscle morphometric data into a model of cervical musculoskeletal anatomy and intervertebral kinematics. Moment arms and force-generating capacity of neck muscles were calculated for a range of head positions. RESULTS: With the head in the upright neutral position, the muscles with the largest moment arms and moment-generating capacities are sternocleidomastoid in flexion and lateral bending, semispinalis capitis and splenius capitis in extension, and trapezius in axial rotation. The moment arms of certain neck muscles (e.g., rectus capitis posterior major in axial rotation) change considerably in the physiologic range of motion. Most neck muscles maintain at least 80% of their peak force-generating capacity throughout the range of motion; however, the force-generating capacities of muscles with large moment arms and/or short fascicles (e.g., splenius capitis) vary substantially with head posture. CONCLUSION: These results quantify the contributions of individual neck muscles to moment-generating capacity and demonstrate that variations in force-generating capacity and moment arm throughout the range of motion can alter muscle moment-generating capacities.

Biomechanical Phenomena↗
PubMed2003

A large complement of the predicted Arabidopsis ARM repeat proteins are members of the U-box E3 ubiquitin ligase family.

The Arabidopsis genome was searched to identify predicted proteins containing armadillo (ARM) repeats, a motif known to mediate protein-protein interactions in a number of different animal proteins. Using domain database predictions and models generated in this study, 108 Arabidopsis proteins were identified that contained a minimum of two ARM repeats with the majority of proteins containing four to eight ARM repeats. Clustering analysis showed that the 108 predicted Arabidopsis ARM repeat proteins could be divided into multiple groups with wide differences in their domain compositions and organizations. Interestingly, 41 of the 108 Arabidopsis ARM repeat proteins contained a U-box, a motif present in a family of E3 ligases, and these proteins represented the largest class of Arabidopsis ARM repeat proteins. In 14 of these U-box/ARM repeat proteins, there was also a novel conserved domain identified in the N-terminal region. Based on the phylogenetic tree, representative U-box/ARM repeat proteins were selected for further study. RNA-blot analyses revealed that these U-box/ARM proteins are expressed in a variety of tissues in Arabidopsis. In addition, the selected U-box/ARM proteins were found to be functional E3 ubiquitin ligases. Thus, these U-box/ARM proteins represent a new family of E3 ligases in Arabidopsis.

Amino Acid Motifs↗
PubMed1997

Muscle balance at the knee--moment arms for the normal knee and the ACL-minus knee.

Forces, moments and stresses at the knee are dependent upon external and internal loading factors including muscle forces, segmental position and velocity, load carried, and the moment arms (mechanical advantage) of the muscle-tendon units. Requisite to prediction of forces and moments is a detailed understanding of effective moment arms throughout the knee range-of-motion (ROM). Existing muscle models for the knee are based upon limited static studies of only a few preserved specimens. The objectives of this report are to develop a comprehensive description of muscle-tendon moment arms for the normal knee and the anterior cruciate ligament (ACL)-minus knee during flexion-extension motion. Recent research results describe two nonorthogonal, nonintersecting axes of motion for the knee--one describing flexion-extension (FE) and the other longitudinal rotation (LR, equivalent to internal-external rotation). The effective flexion-extension moment arms of the muscles crossing the knee were developed with respect to the FE axis in 15 fresh, hemi-pelvis cadaver specimens. The normal moment arms for each of 13 muscles plus the patellar tendon exhibited variable, yet repeatable and recognizable patterns throughout the ROM. For most muscles there was no significant difference between the normal and ACL-minus moment arms. The results provide a basis for more accurate predictions of joint reaction forces and moments as well as useful knowledge for practitioners and therapists to assist in the assessment of muscle balance at the knee following injury, repair, and throughout rehabilitation.

Adult↗
PubMed1976

Hyperactivity and faster replicating property of the two arms of the male X of Drosophila pseudoobscura.

The two arms of the X chromosome of Drosophila pseudoobscura have different phylogenetic origin, the XL being homologous to the X and the XR homologous to the 3L of D. melanogaster. The replicative and transcriptive activities of the two arms have been examined in order to understand how such phylogenetically different components of the X contribute toward the chromosomal basis of dosage compensation. The 3H-uridine labelled autoradiograms of the polytene chromosomes of larval salivary glands reveal that the intensity of labelling in the XL and XR of the male is not significantly different from that in the two arms of the female, respectively. The number of grains on the two arms plotted against the grain number on an autosome follows a linear regression, and neither slope in the male is significantly different from its counterpart in the female. The 3H-thymidine autoradiograms show that in all phases of replication, viz. initial, middle and terminal, both arms of the X chromosome in the male are advanced by one step in the cycle. Results, therefore, suggest that both arms of the X of D. pseudoobscura, are hyperactive and faster replicating in the male. Such a situation might arise due to a primary signal coming from autosomally located regulators controlling the super-operon structure of the X chromosomal genes.

Animals↗
PubMed2006

Bacterial risk reduction by improved donor arm disinfection, diversion and bacterial screening.

The Interventions of improved donor arm disinfection, diversion and bacterial screening have been implemented by blood services and shown to have substantial benefit. The major source of bacterial contamination is donor arm derived. Blood services are now introducing best practice donor arm disinfection techniques. Diversion has been shown to substantially reduce bacterial contamination in the order of 40-88%. Diversion, together with improved donor arm disinfection, has shown to improve the percentage of reduction in contamination from 47% to 77%. Residual contamination levels after the Introduction of diversion and improved donor arm disinfection may be in the order of 30-40%. Numerous countries have now implemented screen testing programmes for platelet concentrates, which are the major source of bacterial transfusion transmission. Pathogen reduction systems have been developed and are under development. At present, concerns remain with these systems regarding cost, process control, ability to inactivate high titres of viruses, killing of bacterial spores, product damage, genotoxicity and mutagenicity. The interventions of diversion, improved donor arm disinfection and bacterial screen testing are currently available, As such they can be implemented now to increase blood safety with no associated patient risk.

Blood Donors↗
PubMed2006

Morphological analysis of the hindlimb in apes and humans. II. Moment arms.

Flexion/extension moment arms were obtained for the major muscles crossing the hip, knee and ankle joints in the orang-utan, gibbon, gorilla (Eastern and Western lowland) and bonobo. Moment arms varied with joint motion and were generally longer in proximal limb muscles than distal limb muscles. The shape of the moment arm curves (i.e. the plots of moment arm against joint angle) differed in different hindlimb muscles and in the same muscle in different subjects (both in the same and in different ape species). Most moment arms increased with increasing joint flexion, a finding which may be understood in the context of the employment of flexed postures by most non-human apes (except orang-utans) during both terrestrial and arboreal locomotion. When compared with humans, non-human great apes tended to have muscles better designed for moving the joints through large ranges. This was particularly true of the pedal digital flexors in orang-utans. In gibbons, the only lesser ape studied here, many of the moment arms measured were relatively short compared with those of great apes. This study was performed on a small sample of apes and thus differences noted here warrant further investigation in larger populations.

Animals↗
PubMedDate not supplied

Analyses of 22S dynein binding to Tetrahymena axonemes lacking outer dynein arms.

Tetrahymena thermophila mutants homozygous for the oad mutation become nonmotile when grown at the restrictive temperature of 39 degrees C. Axonemes isolated from nonmotile oad mutants (oad 39 degrees C axonemes) lack approximately 90% of their outer dynein arms and are deficient in 22S dynein. Here we report that oad 39 degrees C axonemes contain 40% of the 22S dynein heavy chains that wild-type axonemes contain and that oad axonemes do not undergo ATP-induced microtubule sliding in vitro. Wild-type 22S dynein will bind to the outer arm position in oad axonemes and restore ATP-induced microtubule sliding in those axonemes. Unlike wild-type 22S dynein, oad 22S dynein does not bind to the outer arm position in oad axonemes. These data indicate that the oad mutation affects some component of the outer arm dynein itself rather than the outer arm dynein binding site. These data also indicate that oad axonemes can be used to assay outer dynein arm function.

Adenosine Triphosphate↗
PubMed2004

Angiotensin-converting enzyme inhibitors (ACEIs) and age-related maculopathy (ARM): cross-sectional findings from the Blue Mountains Eye Study.

PURPOSE: To assess the relationship between the use of angiotensin-converting enzyme inhibitors (ACEIs) and prevalence of age-related maculopathy (ARM). METHODS: Eligible residents aged >/= 49 years were first examined in 1992-94 (Cross-section 1, n = 3654). Of these, 2335 were re-examined in 1997-99, together with an additional 1174 who became eligible after 1994 (Cross-section 2, n = 3509). Information regarding ACEI use was obtained and retinal photographs were graded using the Wisconsin ARM Grading System. RESULTS: In Cross-section 1, prevalence rates of late and early stage ARM were 1.3% and 4.3% among current ACEI users, and 2.0% and 4.8% among non-current users, respectively. In Cross-section 2, prevalence rates of late and early stage ARM were 2.3% and 11.3% among current ACEI users, and 1.3% and 9.3% among non-current users, respectively. After adjusting for age, sex and smoking, neither survey found any significant association between ACEI use and prevalence of either late or early ARM. CONCLUSIONS: No significant cross-sectional associations were found between ACEI use and ARM prevalence in this population.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Multiplex ARMS-RFLP: a simple and rapid method for HLA-DR4 subtyping.

We have developed a simple and rapid non-radioactive technique for HLA-DR4 subtyping. A multiplex ARMS-RFLP (Amplification Refractory Mutation System--Restriction Fragment Length Polymorphism) system allows HLA-DR4 subtyping by analysis of the products of two multiplex ARMS reaction mixtures. For some cases, restriction enzyme digests (Hae II and/or SacII) of the products are analysed. The technique relies on the fact that an ARMS primer with a mismatch at its 3'-end with respect to the template will not be elongated under PCR conditions. Hence, by designing ARMS primers such that different HLA-DR4 alleles yield PCR products of different lengths, only two reactions, each using a mixture of different ARMS primers, are sufficient to type all of the known HLA-DR4 alleles. This system can distinguish between HLA-DR4 'homozygotes' and 'heterozygotes' since every HLA-DR4 allele can be detected. The ARMS conditions were optimized using DNA from cell lines. This technique has now been used to type a panel of rheumatoid arthritis patients and controls.

Alleles↗
PubMed2003

Tolerability of malaria chemoprophylaxis in non-immune travellers to sub-Saharan Africa: multicentre, randomised, double blind, four arm study.

OBJECTIVE: To compare the tolerability of malaria chemoprophylaxis regimens in non-immune travellers. DESIGN: Randomised, double blind, study with placebo run-in phase. SETTING: Travel clinics in Switzerland, Germany, and Israel. MAIN OUTCOME MEASURE: Proportion of participants in each treatment arm with subjectively moderate or severe adverse events. PARTICIPANTS: 623 non-immune travellers to sub-Saharan Africa: 153 each received either doxycycline, mefloquine, or the fixed combination chloroquine and proguanil, and 164 received the fixed combination atovaquone and proguanil. RESULTS: A high proportion of patients reported adverse events, even in the initial placebo group. No events were serious. The chloroquine and proguanil arm had the highest proportion of mild to moderate adverse events (69/153; 45%, 95% confidence interval 37% to 53%), followed by mefloquine (64/153; 42%, 34% to 50%), doxycycline (51/153; 33%, 26% to 41%), and atovaquone and proguanil (53/164; 32%, 25% to 40%) (P = 0.048 for all). The mefloquine and combined chloroquine and proguanil arms had the highest proportion of more severe events (n = 19; 12%, 7% to 18% and n = 16; 11%, 6% to 15%, respectively), whereas the combined atovaquone and proguanil and doxycycline arms had the lowest (n = 11; 7%, 2% to 11% and n = 9; 6%, 2% to 10%, respectively: P = 0.137 for all). The mefloquine arm had the highest proportion of moderate to severe neuropsychological adverse events, particularly in women (n = 56; 37%, 29% to 44% versus chloroquine and proguanil, n = 46; 30%, 23% to 37%; doxycycline, n = 36; 24%, 17% to 30%; and atovaquone and proguanil, n = 32; 20%, 13% to 26%: P = 0.003 for all). The highest proportion of moderate or severe skin problems were reported in the chloroquine and proguanil arm (n = 12; 8%, 4% to 13% versus doxycycline, n = 5; 3%, 1% to 6%; atovaquone and proguanil, n = 4; 2%, 0% to 5%; mefloquine, n = 2; 1%, 0% to 3%: P = 0.013). CONCLUSIONS: Combined atovaquone and proguanil and doxycyline are well tolerated antimalarial drugs. Broader experience with both agents is needed to accumulate reports of rare adverse events.

Adolescent↗
PubMed1980

Partial trisomy of the short arm of chromosome 8 resulting from balanced maternal translocation.

Extra chromosomal material on the long arm of chromosome 15 was found in an infant with growth retardation, dysmorphic features, skeletal abnormalities, and congenital heart defect. The phenotypically normal mother had a balanced translocation between the short arm of chromosome 8 and the long arm of chromosome 15: 46,XX,t(8:15)(p12:q25). Thus, the patient was partially trisomic for the short arm of chromosome 8 (p12 leads to pter). Comparison of the clinical data obtained from patients with partial trisomy of the short arm of chromosome 8 with those of full trisomy 8 (Warkany's syndrome) suggests that most of the clinical features of Warkany's syndrome require excess material from both the short and long arm of chromosome 8.

Chromosomes, Human, 6-12 and X↗