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Biomedical subjects

A Goldman

Publications and source records attributed to A Goldman.

At least 127 records · Page 7Linked to original sources
PubMed1993

Structure of an interleukin-1 beta mutant with reduced bioactivity shows multiple subtle changes in conformation that affect protein-protein recognition.

Site-specific mutagenesis was used to obtain the human interleukin-1 beta mutant protein with glycine substituted for threonine at position 9 (IL-1 beta Thr9Gly). The mutant maintains receptor binding but exhibits significantly reduced biological activity. The crystal structure of IL-1 beta Thr9Gly has been determined at 2.4-A resolution by molecular replacement techniques and refined to a crystallographic R-factor of 19.0%. IL-1 beta Thr9Gly crystallizes in a different space group (P6(5)22) than does native IL-1 beta (P4(3)); thus the molecules pack differently. Their overall structure is similar, nevertheless, with both composed of 153 amino acids which form 12 antiparallel beta-strands. However, significant conformational differences both close to and far from the site of the mutation may explain the mutant's altered properties.

Amino Acid Sequence↗
PubMed1993

Regulation of parental alloreactivity by reciprocal F1 hybrids. The role of lactation.

Adult reciprocal F1 hybrids differ in their susceptibility to parental graft versus host (GvH) reactions. These reactions were lower when the donor strain was syngeneic with the maternal one. Splenocytes from the member of the reciprocal pair in which the GvH reactions were lower also induced a decreased response of parental cells in cytotoxicity assays and in mixed lymphocyte reactions (MLR). The treatment with anti-CD8 plus complement was able to abrogate the different stimulatory ability of the reciprocal F1 spleen populations. Foster-nursing of F1 hybrids on mothers from the paternal strain was able to induce permanent alterations in the ability of their splenocytes to induce both parental anti-F1 MLR and CTL. The stimulatory ability was indistinguishable from that observed in the reciprocal F1 combination nursed on its own mother. Moreover, lactation was able to alter the ability of CD8+ spleen cells to regulate CTL and parental anti-F1 MLR. The results reported herein show the existence of a maternal effect acting though milk capable of altering the regulation of parental alloreactive T reactions towards self histocompatibility antigens.

Animals↗
PubMed1993

Pain management.

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Analgesia, Patient-Controlled↗
PubMed1992

Comparison of integrated systemic and emotionally focused approaches to couples therapy.

This study compared couples receiving two marital therapy approaches and a control group over a 10-week treatment period. Integrated systemic therapy (IST) and an emotionally focused approach (EFT) were both found to be superior to the control and to be equally effective in alleviating marital distress, facilitating conflict resolution and goal attainment, and reducing target complaints at termination. IST couples, however, showed greater maintenance of gains from termination to 4-month follow-up on marital satisfaction and goal attainment. Clients' perceptions of how change occurred and issues related to the use of a team of observers in IST are discussed.

Adult↗
PubMed1992

The effect of dietary changes and intentional weight loss on high density cholesterol levels in older adults.

The effect of a behaviorally-oriented program to reduce calories and increase physical activity on HDL cholesterol level was evaluated in overweight older adult subjects (n = 31). HDL cholesterol increased from 45.8 to 52.1 mg/dl (p < .0003), and total mean cholesterol increased from 238.0 to 249.5 mg/dl (p < .05). Body weight decreased from 175.0 lbs to 172.6 lbs (p < .03). Analysis of baseline and 40 week food frequency questionnaires indicated that the mean caloric intake had decreased from 1535 to 1303 kcal/day (p < .02), and total fat intake decreased by 9.8 gm/day (p < .01). Weight loss accounted for 13% of the variance in HDL cholesterol change (p < .05). Decreasing fat intake resulted in a smaller increase in HDL cholesterol (F, (1,29) = 5.91, p < .03). Our findings provide further support that a prudent approach to weight reduction can be beneficial in an older adult population.

Aged↗
PubMed1992

Syphilitic gastritis in an HIV-infected individual.

We report the first known case of syphilitic gastritis in an HIV-infected person. The presentation of nonspecific abdominal pain and weight loss in a 48-yr-old former intravenous drug user previously treated for asymptomatic syphilis led to a barium swallow which demonstrated linitis plastica. Upper endoscopy reinforced a suspicion of carcinoma, but biopsy made the diagnosis of syphilis by silver staining. Further testing revealed a positive serology for syphilis as well as HIV infection with a depressed CD-4 lymphocyte count. Treatment with parenteral penicillin led to a rapid resolution of symptoms. This case represents a rare complication of late syphilis, and is another example of the unusual manifestations of syphilis seen in the HIV-infected population.

Gastritis↗
PubMed1991

Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein.

The three-dimensional structure of acetylcholinesterase from Torpedo californica electric organ has been determined by x-ray analysis to 2.8 angstrom resolution. The form crystallized is the glycolipid-anchored homodimer that was purified subsequent to solubilization with a bacterial phosphatidylinositol-specific phospholipase C. The enzyme monomer is an alpha/beta protein that contains 537 amino acids. It consists of a 12-stranded mixed beta sheet surrounded by 14 alpha helices and bears a striking resemblance to several hydrolase structures including dienelactone hydrolase, serine carboxypeptidase-II, three neutral lipases, and haloalkane dehalogenase. The active site is unusual because it contains Glu, not Asp, in the Ser-His-acid catalytic triad and because the relation of the triad to the rest of the protein approximates a mirror image of that seen in the serine proteases. Furthermore, the active site lies near the bottom of a deep and narrow gorge that reaches halfway into the protein. Modeling of acetylcholine binding to the enzyme suggests that the quaternary ammonium ion is bound not to a negatively charged "anionic" site, but rather to some of the 14 aromatic residues that line the gorge.

Acetylcholine↗
PubMed1991

Infrared measurements of HF and HCl total column abundances above Kitt Peak, 1977-1990: seasonal cycles, long-term increases, and comparisons with model calculations.

Series of high-resolution (approximately 0.01 cm-1) solar absorption spectra recorded with the McMath Fourier transform spectrometer on Kitt Peak (altitude 2.09 km, 31.9 degrees N, 111.6 degrees W) have been analyzed to deduce total column amounts of HF on 93 different days and HCl on 35 different days between May 1977 and June 1990. The results are based on the analysis of the HF and H35Cl (1-0) vibration-rotation band R(1) lines which are located at 4038.9625 and 2925.8970 cm-1, respectively. All of the data were analyzed using a multilayer, nonlinear least squares spectral fitting procedure and a consistent set of spectroscopic line parameters. The results indicate a rapid increase in total HF and a more gradual increase in total HCl with both trends superimposed on short-term variability. In addition, the total columns of both gases undergo a seasonal cycle with an early spring maximum and an early fall minimum, with peak-to-peak amplitudes equal to 25% for HF and 13% for HCl. In the case of HF, the changes over the 13 years of measurement are sufficiently large to determine that a better fit is obtained assuming a linear rather than an exponential increase with time. For HCl, linear and exponential models fit the data equally well. Referenced to calendar year 1981.0 and assuming a sinusoidal seasonal cycle superimposed on a linear total column increase with time, HF and HCl increase rates of (10.9 +/- 1.1)% yr-1 and (5.1 +/- 0.7)% yr-1 and total columns of (3.17 +/- 0.11) x 10(14) and (1.92 +/- 0.06) x 10(15) molecules cm-2 (2 sigma) are derived, respectively; the corresponding best fit mean exponential increase rates are equal to (7.6 +/- 0.6)% yr-1 and (4.2 +/- 0.5)% yr-1 (2 sigma). Over the 13-year observing period, the HF and HCl total columns increased by factors of 3.2 and 1.8, respectively. Based on HF and HCl total columns deduced from measurements on the same day, the HF/HCl total columns ratio increased from 0.14 in May 1977 to 0.23 in June 1990. Short-term temporal variations in the HF and HCl total columns are highly correlated; these fluctuations are believed to be caused by dynamical variability in the lower stratosphere. The results of this investigation are compared with previously reported measurements and with time-dependent, two-dimensional model calculations of HF and HCl total columns based on emission histories and photo-oxidation rates for the source molecules.

Astronomical Phenomena↗
PubMed1991

Neonatal thymic contrasuppressor activity on graft versus host reactions towards self histocompatibility antigens. Parental effects.

The ability of fetal and neonatal F1 thymocytes to regulate parental graft versus host (GvH) reactions against self histocompatibility antigens was investigated. The results obtained showed that: (1) fetal F1 thymocytes were able to suppress both maternal and paternal GvH reactivity; (2) at birth, thymocytes were still able to suppress maternal GvH reactivity while no suppression of paternal reactions was detected; the ability to suppress maternal GvH reactions could be detected until day 3; (3) the loss of suppressor activity correlated with the ability of thymocytes to contrasuppress parental GvH reactions. Thus, 24-h F1 thymocytes showed contrasuppressor activity on paternal GvH reactivity and 4-day thymocytes on maternal reactivity. Thymic cells with contrasuppressor activity were shown to be Lyt-1+, CD4+, CD8- and adherent to Vicia villosa. These results suggest the existence of parental effects influencing the duration of thymic suppression and the subsequent appearance of contrasuppressor activity on GvH reactions against self histocompatibility antigens, according to the maternal or paternal origin of self antigens towards which the reaction is directed.

Animals↗
PubMed1991

Pain management in children.

Interest in the management and study of pain in children has increased in recent years. A range of techniques appropriate to children with different developmental levels is now available for the assessment of various aspects of childhood pain. A management plan can be developed depending on the cause of pain and choosing from a range of therapeutic techniques. It should take into account both the physical and psychological aspects of pain. Drugs from the mainstay of treatment of pain with a clear physiological cause. Suitable drugs are now available but inexperience and myths may still result in reluctance to use appropriate strong analgesics in children. Postoperative pain control and the analgesic needs of neonates have been particularly neglected areas. Management can be dramatically improved by increasing staff sensitivity and the use of an integrated programme of drugs, physical techniques and psychological approaches.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Dynamic aspects of cytoskeletal and karyoskeletal intermediate filament systems during the cell cycle.

IF are major cytoskeletal and karyoskeletal components of eukaryotic cells (Steinert and Roop 1988). In numerous instances, their constituent protein subunits have been shown to be substrates for a variety of kinases such as A-kinase, C-kinase, and Ca++/calmodulin kinase (Geisler and Weber 1988; Inagaki et. 1988; Ando et al. 1991), as well as p34cdc2 (Chou et al. 1990; Peter et al. 1990; Ward and Kirschner 1990; Dessev et al. 1991). To date, all of the phosphorylation sites that have been mapped are in the non-alpha-helical amino- or carboxy-terminal domains (Steinert 1988; Ando et al. 1989, 1991; Geisler et al. 1989; Chou et al. 1991), and these secondary modifications can lead to IF reorganization and/or disassembly in vivo and in vitro (see, e.g., Iganaki et al. 1988; Lamb et al. 1989; Chou et al. 1990; Peter et al. 1990; Heald and McKeon 1990; Dessev et al. 1991). In addition, it is possible that the exchange seen between subunits and polymerized IF in interphase following the microinjection of unpolymerized protein (Vikstrom et al. 1989; Miller et al. 1991) may also be regulated in some fashion by phosphorylation/dephosphorylation reactions. In cultured fibroblasts such as BHK-21, the interphase equilibrium state that favors IF polymerization is shifted dramatically to a disassembled state in mitosis, apparently due to enhanced phosphorylation at specific sites mediated through the activity of p34cdc2. However, in other cells in mitosis, such as HeLa, the mechanisms involved in the regulation of cytoskeletal IF remain unclear. Therefore, no one common mechanism appears to be responsible for IF regulation during cell division. On the basis of the majority of data available, it appears that the regulation of IF phosphorylation plays an important role in the regulation of the supramolecular organization of IF cytoskeletal and karyoskeletal networks, especially in the remodeling events that take place as cells enter and exit mitosis. Although the functional significance of IF phosphorylation during interphase is not as obvious as it is in some mitotic cells, we are tempted to speculate that there may be a connection with mechanisms involved in signal transduction, since IF proteins appear to be targets for kinases known to be activated by second messengers such as Ca++ and cAMP.

Animals↗
PubMed1991

Prevention of cytomegalovirus infection following bone marrow transplantation: a randomized trial of blood product screening.

From 1983 to 1987, cytomegalovirus seronegative allogeneic bone marrow recipients were randomized to receive screened cytomegalovirus (CMV) seronegative or unscreened blood products and 125 patients were available for analysis. CMV infection occurred in 18% of patients in the screened versus 38% in the unscreened blood product group. However, only two of 64 patients in the screened group and seven of 61 in the unscreened group developed culture or biopsy-proven CMV infections. Bone marrow donor CMV seropositivity was associated with an increased risk of developing CMV infection (21% with seronegative and 46% with seropositive donor), and CMV infection was not prevented by blood product screening if the bone marrow donor was sero = positive (62% for screened, 42% for unscreened group, p = 0.80). One year survival censored for relapse was 52% in the screened group versus 68% in the unscreened group (p = 0.08). Gram negative bacteremia complicated bone marrow transplantation (BMT) in 35% of patients receiving screened and 15% of those receiving unscreened blood products (p = 0.02). Relapse did not differ in the screened and unscreened groups. By multivariate analysis, high risk disease (p = 0.0002), CMV infection (p = 0.004), screened blood products group (p = 0.011), recipient age greater than 17 (p = 0.027), chronic graft-versus-host disease (p = 0.014) and gram negative bacteremia (p = 0.004) independently had a negative influence on survival. We conclude that blood product screening was effective in preventing CMV infections following BMT if both the recipient and bone marrow donor were CMV seronegative.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

The crystal structure of the catalytic domain of the site-specific recombination enzyme gamma delta resolvase at 2.7 A resolution.

The crystal structure of the catalytic domain of the site-specific recombination enzyme gamma delta resolvase has been determined at 2.7 A resolution. Its first 120 amino acids form a central five-stranded, beta-pleated sheet surrounded by five alpha helices. In one of the four dyad-related dimers, the two active site Ser-10 residues are 19 A apart, perhaps close enough to contact and become covalently linked to the DNA at the recombination site. This dimer also forms the only closely packed tetramer found in the crystal. The subunit interface at a second dyad-related dimer is more extensive and more highly conserved among the homologous recombinases; however, its active site Ser-10 residues are more than 30 A apart. Side chains, identified by mutations that eliminate catalysis but not DNA binding, are located on the subunit surface near the active site serine and at the interface between a third dyad-related pair of subunits of the tetramer.

Binding Sites↗
PubMed1990

A helix-turn-strand structural motif common in alpha-beta proteins.

By exhaustive structural comparisons, we have found that about one-third of the alpha-helix-turn-beta-strand polypeptides in alpha-beta barrel domains share a common structural motif. The chief characteristics of this motif are that first, the geometry of the turn between the alpha-helix and the beta-strand is somewhat constrained, and second, the beta-strand contains a hydrophobic patch that fits into a hydrophobic pocket on the alpha-helix. The geometry of the turn does not seem to be a major determinant of the alpha-beta unit, because the turns vary in length from four to six residues. However, the motif does not occur when there are few constraints on the geometry of the turn-for instance, when the turns between the alpha-helix and the beta-strands are very long. It also occurs much less frequently in flat-sheet alpha-beta proteins, where the topology is much less regular and the amount of twist on the sheet varies considerably more than in the barrel proteins. The motif may be one of the basic building blocks from which alpha-beta barrels are constructed.

Alcohol Dehydrogenase↗