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Biomedical subjects

B Martin

Publications and source records attributed to B Martin.

At least 19 recordsLinked to original sources
PubMed2025

HLA-E and NKG2A Mediate Resistance to BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) is the first-line therapy for high-grade non-muscle-invasive bladder cancer (NMIBC), yet many patients experience recurrence due to immune evasion. We identify HLA-E and NKG2A as mediators of adaptive resistance involving chronic activation of NK and T cells in BCG-unresponsive tumors. Prolonged IFN-γ exposure enhances HLA-E and PD-L1 expression on recurrent tumors, accompanied by the accumulation of NKG2A+ NK and CD8 T cells. HLA-Ehigh tumor cells preferentially cluster near CXCL12-rich stromal regions with dense effector cell presence, underscoring a spatially segregated tumor architecture. Although cytotoxic lymphocytes retain effector potential, their activity is restrained by HLA-E/NKG2A and PD-L1/PD-1 pathways located in their immediate neighborhood within the bladder tumor microenvironment. These data reveal a spatially organized immune escape program that limits anti-tumor immunity. Our findings support dually targeting NKG2A and PD-L1 checkpoint blockade as a rational, bladder-sparing strategy for patients with BCG-unresponsive NMIBC.

BCG-unresponsive↗
PubMed1992

Limited proteolysis reveals a structural difference in the globular head domains of dephosphorylated and phosphorylated Acanthamoeba myosin II.

Phosphorylation at three sites at the tip of the tail of myosin II from Acanthamoeba castellanii inactivates the actin-activated Mg(2+)-ATPase activity of filamentous myosin and the in vitro motility activity of both monomeric and filamentous myosin. To seek a structural explanation for these effects, we examined the susceptibilities of dephosphorylated and phosphorylated myosins II to endoproteinases. Endoproteinase Arg-C cleaved myosin II preferentially at two sites in the globular head, Lys-621 and Arg-638, producing an NH2-terminal fragment of about 67,000 Da and a COOH-terminal fragment of about 112,000 Da. Dephosphorylated monomers and filaments were cleaved about 3 times more rapidly than their phosphorylated counterparts principally because of a much greater rate of cleavage at Arg-638; the ratio of cleavage at Arg-638:Lys-621 was about 3 for dephosphorylated myosins and about 0.5 for phosphorylated myosins. These data demonstrate that phosphorylation at the tip of the tail of Acanthamoeba myosin II causes a conformational change in the globular head that contains the catalytic sites; therefore, this conformational change may be related to the different catalytic and motile activities of the dephosphorylated and phosphorylated enzymes.

Acanthamoeba↗
PubMed1992

Identification of synthetic retinoids with selectivity for human nuclear retinoic acid receptor gamma.

The action of retinoids on gene regulation is mediated by three distinct nuclear retinoic acid receptor (RAR) subtypes called RAR alpha, beta and gamma. Since RAR gamma is predominantly expressed in adult skin, specific ligands for this subtype could (i) represent valuable tools to evaluate the biological role of RAR gamma in skin and (ii) provide therapeutic entities with a higher therapeutic index at lower teratogenic risk. Using in vitro binding studies and a functional transactivation assay, we have identified three compounds with high RAR gamma selectivity.

Animals↗
PubMed1992

A highly conserved repeated DNA element located in the chromosome of Streptococcus pneumoniae.

We report the discovery of a group of highly conserved DNA sequences located, in those cases studied, within intergenic regions of the chromosome of the Gram positive Streptococcus pneumoniae. The S. pneumoniae genome contains about 25 of these elements called BOX. From 5' to 3', BOX elements are composed of three subunits (boxA, boxB, and boxC) which are 59, 45 and 50 nucleotides long, respectively. BOX elements containing one, two and four copies of boxB have been observed; boxB alone was also detected in one instance. These elements are unrelated to the two most thoroughly documented families of repetitive DNA sequences present in the genomes of enterobacteria. BOX sequences have the potential to form stable stem-loop structures and one of these, at least, is transcribed. Most of these elements are located in the immediate vicinity of genes whose product has been implicated at some stage in the process of genetic transformation or in virulence of S. pneumoniae. This location raises the intriguing possibility that BOX sequences are regulatory elements shared by several coordinately controlled genes, including competence-specific and virulence-related genes.

Base Sequence↗
PubMed1992

Preparation of a phospholipid-insensitive, autophosphorylation-activated catalytic fragment of Acanthamoeba myosin I heavy chain kinase.

The actin-activated Mg(2+)-ATPase activity of Acanthamoeba myosin I depends on phosphorylation of its single heavy chain. The activity of the myosin I heavy chain kinase is increased about 50-fold by autophosphorylation, and the rate of kinase autophosphorylation is enhanced about 20-fold by acidic phospholipids independent of the presence of Ca2+ (Brzeska, H., Lynch, T. J., and Korn, E. D. (1990) J. Biol. Chem. 265, 3591-3594). In this paper, we show that chymotryptic digestion of the kinase produces a 54-kDa fragment which contains three to four of the approximately 11 original phosphorylation sites and whose activity is greatly stimulated by autophosphorylation. However, both the rate of autophosphorylation and the kinase activity of the 54-kDa fragment are independent of phospholipid and comparable to those of intact kinase in the presence of phospholipid. These data imply that the (probably NH2-terminal) region(s) removed by proteolysis is necessary for phospholipid-sensitive inhibition of autophosphorylation of sites residing within the (probably COOH-terminal) 54-kDa fragment. The 54-kDa fragment contains the catalytic site of the kinase as well as three to four sites whose phosphorylation is necessary for full expression of kinase activity. The middle region of the kinase molecule contains proline-rich regions that are similar to the COOH-terminal tail of the kinase substrate, Acanthamoeba myosin I.

Acanthamoeba↗
PubMed1992

A theory of fatigue damage accumulation and repair in cortical bone.

An analysis is presented of the balance between the accumulation and repair of fatigue damage in osteonal bone. Fatigue damage is defined in terms of cracks seen histologically when precautions are taken to avoid preparation artifact. The rate of occurrence of such damage is assumed to be proportional to the product of applied peak-to-peak stress, raised to a power, and the loading frequency. The rate of damage repair is assumed to be proportional to the activation rate for osteonal remodeling, and to the mean cross-sectional area of the resulting osteons. An additional factor is introduced to account for the possibility that damage provokes nearby remodeling. The theory is used to compare data from previous experiments of two types: fatigue-to-failure, and studies in which histologically observable cracks are made more numerous by repetitive loading. The analysis shows that there is a measure of agreement between the results of the two kinds of experiments, but the current data are too limited, and the results are too dependent on the mode of loading, to adequately test the theory. However, the analysis provides a framework for designing experiments to more efficiently clarify the relationships between fatigue failure, cracks seen in histologic sections, and the rate at which such cracks are repaired by osteonal remodeling.

Biomechanical Phenomena↗
PubMed1992

Recombinant congenic strains of mice from B10.D2 and DBA/2: their contribution to behavior genetic research and application to audiogenic seizures.

Recombinant congenic strains (RCS) represent a series of related strains, each of which carries a small fraction of the genome of one strain ("donor" strain) on the genetic background of another strain ("background" strain). Recombinant inbred strains (RIS) are commonly used to identify major gene segregation and linkage and associations between behavior and quantitative trait loci, whereas recombinant congenic strains (RCS) open other complementary leads. The variability in the reactivity of RCS to a trait is thus the expression of few minor-effect genes originating from the donor strain, because the probability that major genes are present in any one RCS is low. Unlike RIS in which minor-effect genes are often masked by major genes, RCS enable the effects of minor genes to be studied. With our method, for a given trait, an estimate can be made of the gene strength distribution as well as an estimate of the minimal number of genes involved having a certain strength.

Acoustic Stimulation↗
PubMed1992

Binding of estrogen-3-sulfates to stallion plasma and equine serum albumin.

The binding of estrone-3-sulfate (E1-3-S) and estradiol-3-sulfate (E2-3-S) to adult stallion plasma was determined and compared with the binding to equine serum albumin (ESA). On the ESA molecule, two binding sites for E1-3-S with an association constant of 1.3 x 10(5) M-1 and several sites of weaker affinity were found; the data for E2-3-S showed the existence of four binding sites of moderate affinity (1 x 10(5) M-1) and several sites of weaker affinity. The removal of albumin from the stallion plasma resulted in the absence of binding of E1-3-S or E2-3-S, whereas the removal of glycoproteins resulted in binding parameters similar to those obtained with whole plasma. These results indicate that ESA is the only estrogen sulfate binder in horse plasma. Under physiological conditions, 95% of E1-3-S was bound to ESA.

Animals↗
PubMed1992

Fluticasone propionate given once daily is as effective for seasonal allergic rhinitis as beclomethasone dipropionate given twice daily.

Fluticasone propionate was compared with beclomethasone dipropionate for the treatment of allergic rhinitis in a multicenter, double-blind, randomized, placebo-controlled study during the mountain cedar (Juniperus ashei) pollination season in central Texas. Adults (n = 313) with moderate to severe symptoms were treated with fluticasone propionate aqueous nasal spray 200 micrograms once a day or beclomethasone dipropionate aqueous nasal spray 168 micrograms twice a day or placebo for 2 weeks. Fluticasone propionate administered once daily and beclomethasone dipropionate administered twice daily were equally effective as assessed by clinician- and patient-rated scores for nasal obstruction, rhinorrhea, sneezing, and nasal itching throughout the treatment and follow-up periods. Both regimens were more effective than placebo. Adverse events were related to topical administration and were similar in frequency and nature in all three treatment groups. Fluticasone propionate and beclomethasone dipropionate displayed a similar safety profile that did not differ from placebo. We conclude that fluticasone propionate aqueous nasal spray administered as 200 micrograms once daily in the morning is as safe and effective as beclomethasone dipropionate aqueous nasal spray administered as 168 micrograms twice daily for seasonal allergic rhinitis.

Administration, Topical↗
PubMed1992

Iron status in exercising women: the effect of oral iron therapy vs increased consumption of muscle foods.

Forty-seven previously sedentary women participating in a 12-wk moderate aerobic-exercise program were randomly assigned to one of four dietary groups: 50-mg/d iron supplement and a low food-iron diet (50 FE + EX), 10-mg/d iron supplement and a low food-iron diet (10 FE + EX), placebo and unrestricted diet (P + EX), and meat supplement and high food-iron diet (M + EX). A sedentary control group (n = 13) received no dietary interventions. Hematocrit, total iron-binding capacity, and hemoglobin, serum iron, serum ferritin, and serum albumin concentrations were measured every 4 wk. Hemoglobin values decreased at the end of 4 wk in all exercising groups compared with the control group. Iron status in the 50 FE + EX and M + EX groups improved after week 4 as indicated by an increase in serum ferritin, serum iron, and hemoglobin concentrations, and a decline in total iron-binding capacity. Thus, short-term, moderate aerobic exercise resulted in compromised iron status that was offset to varying degrees by ingesting iron or meat supplements. However, meat supplements were more effective in protecting hemoglobin and ferritin status than were iron supplements.

Adolescent↗
PubMed1992

Infectious and mechanical complications of central venous catheters placed by percutaneous venipuncture and over guidewires.

OBJECTIVE: To compare the frequency of infectious and mechanical complications of central venous and pulmonary artery catheters placed by initial venipuncture vs. over a guidewire at existing sites. HYPOTHESIS: Exchange of central venous catheters and pulmonary artery catheters over a guidewire as opposed to fresh venipuncture reduces mechanical complications without increasing risk of infection. DESIGN: Chart audit. PATIENTS: Medical, surgical, and coronary ICU patients requiring invasive monitoring or central venous access. INTERVENTIONS: Patients requiring prolonged catheterization underwent periodic exchange of catheters over a guidewire. Rates of catheter-related infections and mechanical complications were determined for central venous catheters placed by initial venipuncture and those catheters placed by guidewire exchange. MEASUREMENTS AND MAIN RESULTS: Over a 12-month period, 939 catheters were inserted in 454 patients. Of these 939 catheters, 534 were placed by guidewire exchange. Use of a guidewire was associated with a decreased frequency of pneumothorax and hemothorax compared with initial venipuncture (0/405 [0%] vs. 7/534 [1.3%], respectively; p < .05) but not with increased risk of infection (9/405 [2.2%] vs. 14/534 [2.6%], respectively; NS). Guidewire-facilitated replacement of multiple consecutive catheters at the same site did not increase the risk of catheter-related infection. Catheters placed via internal jugular veins were more likely to become infected than catheters placed via subclavian veins (17/477 [3.6%] vs. 3/430 [0.7%], respectively; p < .01). CONCLUSIONS: When prolonged central venous or pulmonary artery catheterization is necessary, periodic catheter replacement over a guidewire is associated with fewer mechanical complications than initial venipuncture. Periodic catheter replacement over a guidewire is also associated with no increase in risk of infection.

Bias↗
PubMed1992

Lung function testing in adults with preferential nasal breathing.

Three adult patients with asthma with preferential nasal breathing were found to have a typical pattern of lung function test results with substantial between test variation. This condition can be identified as a cause of unsatisfactory performance in respiratory tests by observing the patient's reaction after the nostrils have been occluded.

Aged↗
PubMed1992

Selective synthetic ligands for human nuclear retinoic acid receptors.

From a series of naphthalene and benzoic acid derivatives we have identified synthetic retinoic acid analogues exhibiting high selectivity for the nuclear retinoic acid receptors RAR alpha (Am 580), RAR beta (CD 2019) and RAR gamma (CD 437) as well as ligands sharing high affinities for all RAR subtypes (CD 367). The compounds were evaluated in two complementary screening systems: (1) binding to nuclear proteins extracted from COS-7 cells after transfection with the appropriate expression vectors, and (2) induction of plasminogen activator in the embryonic mouse teratocarcinoma cell line F9. All compounds behaved as retinoic acid agonists in the F9 test.

Binding, Competitive↗
PubMed1992

Unbalanced karyotype due to adjacent 1 segregation of t(11;22)(q23.3;q13.2).

The 11q;22q translocations, whatever the breakpoints may be, are of particular interest because of their propensity to 3:1 segregation of the chromosomes at meiosis I. Until now, no unbalanced karyotype resulting from 2:2 adjacent segregation was published among offspring of 11q;22q translocation carriers. The authors report the case of an unbalanced karyotype due to adjacent 1 segregation of a maternal translocation (11;22)(q23.3;q13.2). The proband's karyotype was 46,XX,-22,+der(22)(11;22)(q23.3;q13.2)mat. This finding demonstrates that adjacent 1 segregation is possible in t(11;22) with breakpoints at 11q23 and 22q13, and can lead to birth of viable infants.

Abnormalities, Multiple↗
PubMed1992

The effect of intra- and intermolecular disulfide bonds after peptide grafting on the properties of yeast alcohol dehydrogenase.

Hydrophilic peptides including cysteine residues were grafted on activated yeast alcohol dehydrogenase. The grafted enzyme preparation was then submitted to oxidation at various concentrations in order to favour the formation of intramolecular or intermolecular disulfide bonds. Intermolecular bonds led to enzyme inactivation. But a rigidification of the enzyme was observed with intramolecular bonds. However, thiol groups also chelated the catalytic and structural zinc atoms, leading to the corresponding enzyme inactivation and thermolability. Formation of intramolecular disulfide bridges after peptide grafting strengthens enzyme conformation and can induce enzyme stabilization, but it has to take into account the possible interference with the naturally occurring cysteine bridges.

Alcohol Dehydrogenase↗
PubMed1991

Comparisons between patterns of convulsions induced by two beta-carbolines in 10 inbred strains of mice.

The beta-carbolines, methyl-beta-carboline-3-carboxylate (beta-CCM) and 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) are known to have pharmacological properties opposite to those of agonistic benzodiazepines. Convulsions induced by these drugs lead to differential patterns, such as clonus, myoclonic or tonic seizures. In 10 different inbred strains of mice we investigated whether the responsiveness to the two drugs was the same, irrespective of the pattern of convulsions. We found the same ranking in the responsiveness of the strains to both drugs in the case of myoclonic seizures. No such correlation could be found for clonus or tonic seizures. Our conclusion is that the same genetic factors determine myoclonic seizures, whereas a plurality of mechanisms underly the other patterns. Thus, myoclonic seizures seem to be the most appropriate index for evaluating the convulsant action of beta-carbolines in genetic experiments.

Animals↗