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Biomedical subjects

A Collins

Publications and source records attributed to A Collins.

At least 19 recordsLinked to original sources

Factors affecting mammographic visualization of the breast after augmentation mammaplasty.

OBJECTIVE: To measure the effect of various parameters on mammographic visualization of the breast after augmentation mammaplasty. DESIGN: Preoperative and postoperative mammography was performed in patients undergoing augmentation mammaplasty. The area of breast tissue visualized on each film was measured. Changes in the area visualized were correlated with a variety of different parameters. SETTING: The Breast Center, Van Nuys, Calif, a free-standing multidisciplinary breast diagnostic and treatment facility. PATIENTS: The 68 women (126 breasts) represent a consecutive sample of patients undergoing augmentation mammaplasty for whom preoperative and postoperative mammograms were available. MAIN OUTCOME MEASURES: Area visualized was correlated with degree of capsular contracture, implant position, type of mammography, preoperative breast size, implant size, and implant type. RESULTS: The major factor affecting mammography is capsular contracture. Little or no capsular contracture results in a 30% reduction in the area visualized; moderate or severe contracture results in a 50% reduction. Other important factors include implant position (improved visualization with implant beneath pectoral muscle) and type of mammography performed (slightly more tissue seen with displacement technique). Very small preoperative breast size yields increased visualization. Implant size and type have little or no effect. CONCLUSIONS: In most women with breast implants, there is a decrease in measurable breast tissue on the postaugmentation mammogram. Capsular contracture and implant position exert a profound effect; type of mammography performed and preoperative breast size are also significant.

Adult

Integration of gene maps: chromosome 1.

A composite map of 177 loci has been constructed in two steps. The first combined pairwise logarithm-of-odds scores on 127 loci into a comprehensive genetic map. Then this map was projected onto the physical map through cytogenetic assignments, and the small amount of physical data was interpolated for an additional 50 loci each of which had been assigned to an interval of less than 10 megabases. The resulting composite map is on the physical scale with a resolution of 1.5 megabases. In the future these methods may be used to incorporate locations from linkage, contigs, radiation hybrids, restriction fragments, and somatic cell maps. Dense, reliable, and well-documented maps are essential for long-range sequencing and to localize and clone disease genes.

Animals

Humanized OKT3 antibodies: successful transfer of immune modulating properties and idiotype expression.

Antibodies that possess the Ag-binding regions of OKT3 within the context of a human framework (Hu-OKT3 Ab) offer distinct advantages for optimizing anti-CD3 mAb therapy. First, manipulation of Ab genes to produce humanized Ab that retain Ag-binding activity may circumvent antigenicity problems. Second, Ab gene engineering provides a means for modifying functional properties, including T cell activation and immune suppression. The purpose of this study was to determine the functional properties of Hu-OKT3 Ab and to compare the functional properties and idiotypes of Hu-OKT3 Ab to those of murine OKT3. Three Hu-OKT3 IgG4 Ab, a chimeric OKT3 antibody (cOKT3-1) (grafted sequences comprising all OKT3 VH and VL regions) and two complementarity determining region (CDR)-grafted antibodies, gOKT3-5 and gOKT3-6 (grafted sequences comprising only OKT3 VH and VL CDR and some framework amino acids, were analyzed. Initial studies demonstrated that the cOKT3 and gOKT3-5 Ab bound selectively to T cells and competitively inhibited OKT3-FITC binding with avidities similar to that of murine OKT3. Binding avidity of the gOKT3-6 Ab was markedly less than that of the other two Hu-OKT3 Ab. Serologic analysis suggested that cOKT3 and gOKT3-5 Ab possess idiotypes (combining sites) similar to murine OKT3. T cell activation potency of all three Hu-OKT3 Ab was assessed by proliferation, induction of activation marker expression (IL-2R and Leu 23), and lymphokine production (TNF-alpha and IFN-gamma). The cOKT3 and gOKT3-5 Ab demonstrated T cell activation potencies similar to murine OKT3 as assessed by each parameter. CD3 coating and modulation by these two Ab was effective but somewhat less potent than that observed with OKT3. Finally, cOKT3 and gOKT3-5 Ab both inhibited CTL activity comparably to murine OKT3. In conclusion, these studies indicate that gOKT3-5 and cOKT3 Ab possess immune modulating properties similar to murine OKT3 and thus offer attractive alternatives to murine OKT3 for in vivo therapy.

Amino Acid Sequence

Workshop on DNA repair.

A workshop on DNA repair with emphasis on eukaryotic systems was held, under the auspices of the EC Concerted Action on DNA Repair and Cancer, at Noordwijkerhout (The Netherlands) 14-19 April 1991. The local organization of the meeting was done under the auspices of the Medical Genetic Centre South-West, The Netherlands (MGC), c/o Department of Radiation Genetics and Chemical Mutagenesis, University of Leiden (The Netherlands). Local organizers were: D. Bootsma (chairman), W. Ferro, J.H.J. Hoeijmakers, A.R. Lehmann, P.H.M. Lohman, L. Mullenders, and A.A. van Zeeland (secretarial assistance: Mrs. C. Escher-van Heerden and Mrs. R. Bontre). Over 190 scientists participated, and the format of the meeting followed that of the 1987 workshop on the 'Molecular Aspects of DNA Repair' (Friedberg et al., 1987). Plenary review talks in the mornings were followed, in the afternoon, by poster viewing in three or four parallel sessions. Groups of 15-20 posters were discussed in detail, and later on, in plenary sessions, chairpersons of the poster discussions reviewed the afternoons' posters. The principal themes of the meeting were the isolation and characterisation of repair genes and proteins, repair in specific sequences, consequences of defective DNA repair, and new methods for detecting DNA damage and repair. Remarkable progress has been made recently in all of these areas, and many exciting new results were presented. It is impossible to summarize all contributions to this (intensive) one-week meeting. Therefore, and for the sake of coherence, presentations that did not fit easily into any of the general themes of the meetings have not been included.

Animals

Perceptions of infertility and treatment stress in females as compared with males entering in vitro fertilization treatment.

OBJECTIVE: To determine gender similarities and differences in perceptions of infertility and anticipated treatment stress in couples enrolling for in vitro fertilization (IVF) treatment. DESIGN: Both partners were evaluated at enrollment of IVF treatment. The evaluation was part of the screening procedure. SETTING: The Department of Obstetrics and Gynecology at a teaching hospital. PATIENTS, PARTICIPANTS: Two hundred consecutive couples who entered an IVF treatment program. MAIN OUTCOME MEASURES: Self-report questionnaire included items on the duration of infertility, degree of social support, effect of infertility on sexual relationship, expected likelihood of achieving pregnancy, anticipation of stress during treatment, and a self-rating scale of emotional reactions to infertility. RESULTS: The women anticipated more stress in IVF treatment but also rated greater degree of social support than the men. Both partners overestimated their chances of a successful treatment outcome. Factor analysis of the Infertility Scale produced three factors that were similar for both sexes. The first factor represented the desire to have a child as a major focus of life with inadequacy of the male role, social functioning and work efficiency, and pressure to have a child following. CONCLUSIONS: Women reported more stress, but the factors affecting stress of infertility were very similar for both partners. The intense focus on having a child was the predominant factor in anticipated stress of IVF treatment for both males and females.

Adult

Steady-state and dynamic properties of cardiac sodium-calcium exchange. Sodium-dependent inactivation.

Sodium-calcium exchange current was isolated in inside-out patches excised from guinea pig ventricular cells using the giant patch method. The outward exchange current decayed exponentially upon activation by cytoplasmic sodium (sodium-dependent inactivation). The kinetics and mechanism of the inactivation were studied. (a) The rate of inactivation and the peak current amplitude were both strongly temperature dependent (Q10 = 2.2). (b) An increase in cytoplasmic pH from 6.8 to 7.8 attenuated the current decay and shifted the apparent dissociation constant (Kd) of cytoplasmic calcium for secondary activation of the exchange current from 9.6 microM to < 0.3 microM. (c) The amplitude of exchange current decreased synchronously over the membrane potential range from -120 to 60 mV during the inactivation, indicating that voltage dependence of the exchanger did not change during the inactivation process. The voltage dependence of exchange current also did not change during secondary modulation by cytoplasmic calcium and activation by chymotrypsin. (d) In the presence of 150 mM extracellular sodium and 2 mM extracellular calcium, outward exchange current decayed similarly upon application of cytoplasmic sodium. Upon removal of cytoplasmic sodium in the presence of 2-5 microM cytoplasmic free calcium, the inward exchange current developed in two phases, a fast phase within the time course of solution changes, and a slow phase (tau approximately 4 s) indicative of recovery from sodium-dependent inactivation. (e) Under zero-trans conditions, the inward current was fully activated within solution switch times upon application of cytoplasmic calcium and did not decay. (f) The slow recovery phase of inward current upon removal of cytoplasmic sodium was also present under the zero-trans condition. (g) Sodium-dependent inactivation shows little or no dependence on membrane potential in guinea pig myocyte sarcolemma. (h) Sodium-dependent inactivation of outward current is attenuated in rate and extent as extracellular calcium is decreased. (i) Kinetics of the sodium-dependent inactivation and its dependence on major experimental variables are well described by a simple two-state inactivation model assuming one fully active and one fully inactive exchanger state, whereby the transition to the inactive state takes place from a fully sodium-loaded exchanger conformation with cytoplasmic orientation of binding sites (E1.3Ni).

Adenosine Triphosphate

Steady-state and dynamic properties of cardiac sodium-calcium exchange. Secondary modulation by cytoplasmic calcium and ATP.

Dynamic responses of cardiac sodium-calcium exchange current to changes of cytoplasmic calcium and MgATP were monitored and analyzed in giant membrane patches excised from guinea pig myocytes. Secondary dependencies of exchange current on cytoplasmic calcium are accounted for in terms of two mechanisms: (a) The sodium-dependent inactivation process, termed I1 modulation, is itself strongly modulated by cytoplasmic calcium. Recovery from the I1 inactivated state is accelerated by increasing cytoplasmic calcium, and the calculated rate of entrance into I1 inactivation is slowed. (b) A second modulation process, termed I2 modulation, is not sodium dependent. As with I1 modulation, the entrance into I2 inactivation takes place over seconds in the absence of cytoplasmic calcium. The recovery from I2 inactivation is a calcium-dependent transition and is rapid (< 200 ms) in the presence of micromolar free calcium. I1 and I2 modulation can be treated as linear, independent processes to account for most exchange modulation patterns observed: (a) When cytoplasmic calcium is increased or decreased in the presence of high cytoplasmic sodium, outward exchange current turns on or off, respectively, on a time scale of multiple seconds. (b) When sodium is applied in the absence of cytoplasmic calcium, no outward current is activated. However, the full outward current is activated within solution switch time when cytoplasmic calcium is applied together with sodium. (c) The calcium dependence of peak outward current attained upon application of cytoplasmic sodium is shifted by approximately 1 log unit to lower concentrations from the calcium dependence of steady-state exchange current. (d) The time course of outward current decay upon decreasing cytoplasmic calcium becomes more rapid as calcium is reduced into the submicromolar range. (e) Under nearly all conditions, the time courses of current decay during application of cytoplasmic sodium and/or removal of cytoplasmic calcium are well fit by single exponentials. Both of the modulation processes are evidently affected by MgATP. Similar to the effects of cytoplasmic calcium, MgATP slows the entrance into I1 inactivation and accelerates the recovery from inactivation. MgATP additionally slows the decay of outward exchange current upon removal of cytoplasmic calcium by 2-10-fold, indicative of an effect on I2 inactivation. Finally, the effects of cytoplasmic calcium on sodium-calcium exchange current are reconstructed in simulations of the I1 and I2 modulation processes as independent reactions.

Adenosine Triphosphate

Dominant genes for colorectal cancer are not rare.

The genetic basis for colorectal cancer was investigated by complex segregation analysis of a published series of consecutive pedigrees ascertained through patients undergoing treatment for colorectal cancer. Analysis favoured a dominant gene or genes with a frequency of 0.006 with a lifetime penetrance of 0.63. These genes account for 81% of colorectal cancer in patients under 35, however, by 65 about 85% are phenocopies.

Adult

Algorithms for a location database.

The algorithms that drive the ldb location database are described. The program captures data on genetic and physical maps and combines information from different sources into a summary map. To assure portability it was developed in Fortran on a SUN SPARCStation under Unix. The algorithms, which combine rule-based seriation with a minimum deviance bootstrap, allow investigators and chromosome committees to produce a composite location in Mb that integrates partial maps. The program and manual are now available from the authors.

Algorithms

The giant cardiac membrane patch method: stimulation of outward Na(+)-Ca2+ exchange current by MgATP.

1. A giant patch method was used to study the stimulatory effect of cytoplasmic MgATP on outward Na(+)-Ca2+ exchange current in inside-out cardiac membrane patches (1-10 G omega seals with 14-24 microns pipette tip diameters) excised from guinea-pig, rabbit and mouse myocytes. 2. To establish the validity of the method with respect to structure, bleb formation was examined with electron microscopy and with confocal fluorescence light microscopy. The blebs, which form as the sarcolemma detaches, excluded intracellular organelles and transverse tubules. The blebbed cells contained normal sarcomeres, sarcoplasmic reticulum, triads and diads. 3. To further establish the validity of the method for ion transport studies, measurements of Na(+)-K+ pump currents and charge movements are described briefly which demonstrate (i) free access to the cytoplasmic membrane side, (ii) MgATP dependence comparable to reconstituted pump (Kd, 94 microns), (iii) fast, rigorous concentration control and (iv) Na(+)-K+ pump densities in the range of whole-cell densities. 4. Stimulation of outward Na(+)-Ca2+ exchange current by MgATP attenuated exchange current decay during step increments of cytoplasmic sodium, shifted the secondary activation of outward exchange current by cytoplasmic calcium to lower free calcium concentrations and, particularly in mouse cardiac sarcolemma, induced cytoplasmic calcium-independent current. 5. Upon removal of MgATP the stimulatory effect usually decayed with a t50 (half-time) of about 3 min. However, the reversal took place much more rapidly (t50, 5-20 s) in patches from individual guinea-pig and rabbit myocyte batches. When decay was rapid, secondary activation by cytoplasmic calcium was shifted to higher free cytoplasmic calcium concentrations (Kd, 10-65 microns-free calcium). 6. With repeated applications of MgATP the rate and magnitude of the stimulatory effect progressively decreased. 7. The Kd for MgATP of the initial rate of stimulation of outward exchange current was 3 mM or greater. When decay was rapid, the steady-state dependence of exchange current on MgATP also had a Kd of 3 mM or greater. 8. Stimulation of Na(+)-Ca2+ exchange current by MgATP occurred in the absence of cytoplasmic calcium with 9 mM-EGTA. 9. The stimulatory effect of 2 mM-MgATP was not inhibited by up to 200 microM of the protein kinase inhibitor 1-(5-isoquinoline sulphonyl)-2-methylpiperazine (H7), or by peptide inhibitors of cyclic AMP-dependent protein kinase, protein kinase C and calcium-calmodulin-dependent protein kinase II.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate

Mechanism of cardiac Na(+)-Ca2+ exchange current stimulation by MgATP: possible involvement of aminophospholipid translocase.

1. The sensitivity of outward Na(+)-Ca2+ exchange current to charged amphiphiles and phospholipids was tested in giant excised inside-out membrane patches from guinea-pig and rabbit myocytes. 2. Screening of membrane surface potentials with dimethonium (10 mM), spermine (200 microM) and spermidine (100 microM) was without effect, while the positively charged ionic detergents hexadecyltrimethylammonium and dodecyltrimethylammonium strongly inhibited steady-state outward exchange current (0.1-10 microM). 3. Interventions expected to increase negative surface charge included treatment of the cytoplasmic surface with phospholipase D, application of dodecylsulphate (1-10 microM), application of the short-chain phosphatidylserine derivative, dicapryl phosphatidylserine (C10PS), and inclusion of 1-3% phosphatidylserine in the hydrocarbon mixture used to coat electrodes. Each intervention strongly stimulated Na(+)-Ca2+ exchange current in a similar way to MgATP, reducing the fractional decay of outward exchange current (inactivation) during application of high cytoplasmic sodium. 4. The MgATP-stimulated exchange current was inhibited with a Ki of approximately 1 microM by pentalysine, which is known to associate with phosphatidylserine head groups. After 'deregulation' of the exchanger by chymotrypsin, pentalysine was without effect. 5. Inclusion in the pipette of 0.2 mM-pyridyldithioethylamine (an oxidizing inhibitor of aminophospholipid translocase) abolished stimulation of outward exchange current by MgATP without inhibiting basal outward exchange current or sodium pump current. 6. Application to the cytoplasmic side of 1.5 mM-diamide, which reportedly decreases membrane phospholipid asymmetry, apparently reversed the effect of MgATP. After treatment with diamide and subsequently with dithiothreitol, Na(+)-Ca2+ exchange current was again stimulated by MgATP. Diamide was without effect when secondary exchange regulation had been previously removed by chymotrypsin. 7. Potassium current carried by the surface potential-sensitive ionophore, nonactin, was stimulated by MgATP when extracellular surface charge had been neutralized. The effect was largest (40-90%) when low ionic strength cytoplasmic solutions were employed, consistent with an increase of negative membrane charge on the cytoplasmic side during MgATP application. 8. Potassium current carried by nonactin was inhibited by MgATP when cytoplasmic surface charge had been neutralized and extracellular solutions of low ionic strength were employed, consistent with a decrease of negative membrane charge on the extracellular side. 9. These results indicate that the stimulatory effect of MgATP on Na(+)-Ca2+ exchange current could involve changes of charged membrane lipids, that the effect probably involves a transmembrane, oxidation-sensitive protein, that pentalysine-sensitive sites are involved, that phosphatidylserine mimics the effect of MgATP, and that the effect extends to a simple surface potential-sensitive ionophore.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate

A variant of glycophorin A resulting from the deletion of exon 4.

We have isolated a variant form of glycophorin A which has a 39 bp deletion corresponding to nucleotides 233 to 270 of the coding sequence, which is exon 4 of the glycophorin A gene. The remainder of the sequence is identical to that of the M phenotype of glycophorin A.

Amino Acid Sequence

Error filtration, interference, and the human linkage map.

Typing error is a major problem in constructing human linkage maps, leading to incorrect orders and inflating map lengths. An error filter is incorporated into multiple pairwise analysis that corrects for inflation of map lengths and improves recovery of the correct order. Multipoint mapping is more sensitive to error, but when its output is adjusted for both error and interference, map lengths are no longer inflated in proportion to the number of loci and are close to those obtained by multiple pairwise analysis.

Algorithms

Identification of a peptide inhibitor of the cardiac sarcolemmal Na(+)-Ca2+ exchanger.

The deduced amino acid sequence of the cardiac sarcolemmal Na(+)-Ca2+ exchanger has a region which could represent a calmodulin binding site. As calmodulin binding regions of proteins often have an autoinhibitory role, a synthetic peptide with this sequence was tested for functional effects on Na(+)-Ca2+ exchange activity. The peptide inhibits the Na(+)-dependent Ca2+ uptake (KI approximately 1.5 microM) and the Nao(+)-dependent Ca2+ efflux of sarcolemmal vesicles in a noncompetitive manner with respect to both Na+ and Ca2+. The peptide is also a potent inhibitor (KI approximately 0.1 microM) of the Na(+)-Ca2+ exchange current of excised sarcolemmal patches. The binding site for the peptide on the exchanger is on the cytoplasmic surface of the membrane. The exchanger inhibitory peptide binds calmodulin with a moderately high affinity. From the characteristics of the inhibition of the exchange of sarcolemmal vesicles, we deduce that only inside-out sarcolemmal vesicles participate in the usual Na(+)-Ca2+ exchange assay. This contrasts with the common assumption that both inside-out and right-side-out vesicles exhibit exchange activity.

Amino Acid Sequence

Comparative experience with smooth and polyurethane breast implants using the Kaplan-Meier method of survival analysis.

Smooth-walled silicone implants have been widely used in breast surgery. Capsular contracture, causing undesirable firmness and spherical deformity, has been a common problem. Recent studies suggest that polyurethane-covered breast implants are associated with a lower incidence of capsular contracture. The statistical methodology employed in some of these studies, however, may be subject to criticism. Between July of 1984 and June of 1990 (72 months), 427 polyurethane breast implants were used in 279 patients and 439 smooth prostheses were used in 250 patients for a variety of aesthetic and reconstructive procedures. The occurrence of capsular contracture was carefully monitored and then analyzed using the Kaplan-Meier method of survival analysis. This method is particularly well suited to analysis of these types of clinical data because it allows for the fact that contractures occur at varying intervals after surgery and that follow-up of patients is incomplete. The probability of capsular contracture with smooth-walled prostheses was found to be significantly greater than with polyurethane-covered implants in each group of patients studied (p less than 0.05). Other complications occurred at a similar rate regardless of prosthesis type. This study supports the belief that polyurethane breast implants have a lower contracture rate; furthermore, it introduces the Kaplan-Meier method for analyzing the outcome of alternative plastic surgical therapies.

Breast