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Biomedical subjects

R Martin

Publications and source records attributed to R Martin.

At least 343 records · Page 19Linked to original sources
PubMed1995

Antigen presentation mediated by recycling of surface HLA-DR molecules.

Class II histocompatibility molecules associate with peptides derived from antigens that are processed in endocytic compartments. Antigen presentation to class II-restricted T cells generally requires newly synthesized class II molecules, associated invariant chain, and HLA-DM. Exceptions to these rules have been reported, but without description of an underlying mechanism. Here we show that presentation of immunodominant epitopes in the haemagglutinin protein of influenza virus and in myelin basic protein correlates with recycling of surface HLA-DR molecules. Truncation of either one of the alpha or beta cytoplasmic tails virtually eliminated internalization of HLA-DR molecules and presentation of haemagglutinin from inactive virus particles. In contrast, the invariant chain-dependent presentation of matrix antigen from the same virus particles was unaffected by these truncations. Thus HLA-DR cytoplasmic tails are not required for the conventional presentation pathway, but jointly contribute a signal for an alternative pathway involving internalization of HLA-DR molecules.

Amino Acid Sequence↗
PubMed1995

Childhood hearing impairment: auditory and linguistic interactions during multidimensional speech processing.

Children with mild-severe sensorineural hearing losses often use hearing aids and aural/oral language as their primary mode of communication, yet we know little about how speech is processed by these children. The purpose of this research was to investigate how the multidimensional information underlying accurate speech perception is processed by children with mild-severe hearing impairments. The processing of the auditory and linguistic dimensions of speech was assessed with a speeded selective-attention task (Garner, 1974a). Listeners were required to attend selectively to an auditory dimension (gender of the talker) and ignore a linguistic dimension (word) and vice versa. The hypothesis underlying the task is that performance for the target dimension will be unaffected by what is happening on the nontarget dimension if the dimensions are processed independently. On the other hand, if the dimensions are not processed independently, listeners will not be able to attend selectively and performance for the relevant dimension will be affected by what is happening on the irrelevant dimension (termed "Garner" interference). Both children with normal hearing (N = 90) and children with hearing impairment (N = 40) showed some degree of Garner interference, implying that the dimensions of speech are not processed independently by these children. However, relative to the children with normal hearing, the children with hearing impairment showed normal Garner interference when attending selectively to the word dimension (normally effective at ignoring talker-gender input) and reduced Garner interference when attending selectively to the talker-gender dimension (more effective at ignoring word input). This pattern of results implies that the auditory dimension has a normal strength-of-processing level that makes it normally distracting and that the linguistic dimension has an underdeveloped strength-of-processing level that makes it easier to ignore in children with hearing impairment.

Adolescent↗
PubMed1995

Protective effects of a recombinant amino-terminal fragment of human bactericidal/permeability-increasing protein in an animal model of gram-negative sepsis.

Bactericidal/permeability-increasing protein (BPI) has bactericidal properties and also binds lipopolysaccharide (LPS). The ability of a recombinant amino-terminal fragment of BPI to protect mice from death after challenge with a number of different strains of Escherichia coli was tested. BPI prevented death in animals challenged with the J5 rough strain but not with smooth strains O111:B4 and O7K1. Protection was associated with a reduction in serum LPS and tumor necrosis factor-alpha levels but not with reduction in blood bacterial counts. BPI was effective at protecting against death in mice injected with purified O111:B4 LPS. Lack of protection after injection with live O111:B4 and O7K1 may be due to production by these models of approximately 1000-fold higher blood bacterial count compared with J5. Thus, BPI is a promising therapy in the treatment of gram-negative septic shock, although the range of organisms against which it is effective remains to be determined.

Animals↗
PubMed1995

Incidence and pathophysiological relevance of postoperative endotoxemia.

Patients who underwent surgical procedures usually develop elevated body temperature, changes of plasma levels of some proteins, and leucocytosis. These alterations are summarized as the postoperative acute-phase reaction. Also endotoxin can induce the described phenomena suggesting that endotoxin may play a role concerning the induction of the acute phase reaction. In order to test that hypothesis we determined endotoxin plasma levels preoperatively and daily postoperatively in patients who were operated on because of goiter (n = 20), colonic, pancreatic and gastric diseases (n = 58). A significant increase of endotoxin plasma levels was found at the first and third day after abdominal surgery whereas after goiter surgery the increase revealed to be only very slight. However, the decrease between the first and second postoperative day in the latter group was again statistically significant suggesting postoperative endotoxemia even after minor operations. Furthermore a correlation between the amount of circulating endotoxin and pulmonary or infectious complications could be established in patients after major operations even at the first postoperative day suggesting a pathogenetic relevance of postoperative endotoxemia.

Acute-Phase Reaction↗
PubMed1995

In vitro activities of 22 beta-lactam antibiotics against penicillin-resistant and penicillin-susceptible viridans group streptococci isolated from blood.

A total of 410 strains of viridans group streptococci isolated consecutively from blood were tested by the microdilution method for in vitro susceptibility to 22 beta-lactam antibiotics. One hundred thirty-eight strains (33.6%) were resistant to penicillin with a MIC range of 0.25 to 8 micrograms/ml. MICs of all beta-lactam agents tested were higher for penicillin-resistant strains than for susceptible strains. These antibiotics were classified into three groups according to their in vitro activities (MICs at which 50 and 90% of the isolates are inhibited). Beta-Lactams of the first group (these included imipenem, cefpirome, FK-037, cefditoren, cefotaxime, ceftriaxone, and cefepime) showed activities higher than or similar to that of penicillin against penicillin-resistant viridans group streptococci. However, 80% of highly penicillin-resistant Streptococcus mitis organisms required cefotaxime and ceftriaxone MICs of > or = 2 micrograms/ml (range, 2 to 16 micrograms/ml). Beta-Lactams of the second group (cefpodoxime, ampicillin, amoxicillin-clavulanate, piperacillin, and cefuroxime) showed lower activities than penicillin. Finally, antibiotics of the third group (cephalothin, oxacillin, ceftazidime, cefixime, cefaclor, cefetamet, cefadroxil, cephalexin, and ceftibuten) showed poor in vitro activities. Therefore, some of the beta-lactam agents included in the first group could be an acceptable alternative in the treatment of serious infections due to strains highly resistant to penicillin, although clinical experience is needed.

Anti-Bacterial Agents↗
PubMed1995

Context effects on misreading and suppression at UAG codons in human cells.

The effect of the 3' codon context on the efficiency of nonsense suppression in mammalian tissue culture cells has been tested. Measurements were made following the transfection of cells with a pRSVgal reporter vector that contained the classical Escherichia coli lacZ UAG allele YA559. The position of this mutation was mapped by virtue of its fortuitous creation of a CTAG MaeI restriction enzyme site. Determination of the local DNA sequence revealed a C-->T mutation at codon 600 of the lacZ gene: CAG-->TAG. Site-directed mutagenesis was used to create a series of vectors in which the base 3' to the nonsense codon was either A, C, G, or U. Suppression of the amber-containing reporter was achieved by cotransfection with genes for human tRNA(Ser) or tRNA(Gln) UAG nonsense suppressors and by growth in the translational error-promoting aminoglycoside drug G418. Nonsense suppression was studied in the human cell lines 293 and MRC5V1 and the simian line COS-7. Overall, the rank order for the effect of changes to the base 3' to UAG was C < G = U < A. This study confirms and extends earlier findings that in mammalian cells 3' C supports efficient nonsense suppression while 3' A is unsympathetic for read-through at nonsense codons. The rules for the mammalian codon context effect on nonsense suppression are therefore demonstrably different from those in E. coli.

Animals↗
PubMed1995

Repeated DNA sequences isolated by microdissection. I. Karyotyping of barley (Hordeum vulgare L.).

We report on microdissection, cloning and sequence, and Southern and fluorescence in situ hybridization (FISH) analysis of one moderately and one highly amplified repetitive DNA element, pHvMWG2314 and pHvMWG2315, respectively, isolated from barley (Hordeum vulgare L.) chromosome arm 3HL. The pHvMWG2315 sequence hybridizes to all 14 telomeric or subtelomeric regions of the barley chromosomes as determined by FISH. The 50 different hybridization sites that include intercalary signals allow the discrimination of all 14 chromosome arms and the construction of a kariotype of barley. The tandemly repeated subtelomeric element of 331 bp exists in all Triticeae species tested (H. vulgare, Agropyron elongatum, Secale cereale, Triticum tauschii, T. turgidum, and T. aestivum). It is AT rich (66%), exibits 84% sequence homology to subfragments of the D genome ¿specific¿ 1-kb element pAs1 of T. tauscii and 75% homology to interspersed genome-specific DNA sequence pHcKB6 from H. chilence. The repetitive sequence pHvMWG2314 is moderately amplified in barley and highly amplified in hexaploid wheat. The in situ experiments revealed no distinct signals on barley chromosomes, indicating a dispersed character for the sequence. The significance of the results for the identification of chromosomes and chromosome aberrations in FISH experiments are discussed.

Base Composition↗
PubMed1995

Visual memory impairment in patients with obsessive-compulsive disorder: a controlled study.

Memory processes were compared in 26 patients presenting DSM-III-R obsessive-compulsive disorder (OCD) with 20 sex-, age- and education-matched normal controls. A significant between-group difference was found: visual memory was significantly lower in OCD, whereas no significant between-group differences in verbal memory were observed. A subsample of 17 OCD were also compared with the 20 control subjects on an explicit-memory free-recall task and an implicit-memory completion task using neutral, obsessive and guilt-responsibility words to test the effects of an emotional verbal input on memory functioning. No between-group difference was found, suggesting that emotionally laden word processing did not modify implicit and explicit memory performances.

Adult↗
PubMed1995

Influence of prior knowledge and experience on the ability to feign mild head injury symptoms in head injured and non-head-injured college students.

The present study investigated the effects of personal knowledge, experience and beliefs about traumatic brain injury (TBI) on persons' ability to successfully feign neuropsychological impairment. Head-injured and non-injured subjects completed the Head Injury Misconception Survey, and were evenly divided into malingering or control (do best) conditions. Subjects were given a scenario which asked them to imagine that they had been in a prior accident and were involved in litigation. They were then asked to either malinger or respond in the best way possible to a battery of neuropsychological tests. While instructions to malinger had a pronounced effect, knowledge of brain injury did not significantly influence an individual's ability to feign neuropsychological impairment. Future directions in the study of malingering are also discussed.

Journal Article↗
PubMed1995

Diversity of T-cell receptor V alpha, V beta, and CDR3 expression by myelin basic protein-specific human T-cell clones.

We sequenced the cDNAs of alpha and beta T-cell receptors (TCRs), including V, J, and CDR3 regions, expressed by 54 myelin basic protein (MBP)-specific T-cell clones generated from the peripheral blood of 15 multiple sclerosis (MS) patients and three normal controls. Thirteen V alpha gene segments, 18 V beta gene segments, 23 CDR3 alpha sequences, and 30 CDR3 beta sequences were represented among these clones. Some CDR3 motifs were common to several clones that shared epitope specificity, while other motifs were common to clones with diverse epitope specificities. The extensive heterogeneity of TCR gene expression in the human immune response to MBP indicates that therapeutic strategies aimed at blocking a limited number of TCRs are unlikely to fully suppress the T-cell response to MBP in vivo.

Amino Acid Sequence↗
PubMed1995

Immunological aspects of experimental allergic encephalomyelitis and multiple sclerosis.

Multiple sclerosis (MS) is the most frequent, demyelinating disease of the central nervous system (CNS) in Northern Europeans and North Americans. Despite intensive research its etiology is still unknown, but a T cell-mediated autoimmune pathogenesis is likely to be responsible for the demyelination. This hypothesis is based both on findings in MS patients and studies of an experimental animal model for demyelinating diseases, experimental allergic encephalomyelitis (EAE). Experiments in EAE have not only demonstrated which myelin antigens are able to induce the demyelinating process but also have determined the characteristics of encephalitogenic T cells, that is, their fine specificity, major histocompatibility complex (MHC) restriction, lymphokine secretion, activation requirements, and T cell receptor (TCR) usage. Based on these findings, highly specific and efficient immune interventions have been designed in EAE and have raised hopes that similar approaches could modulate the disease process in MS. Although the examination of the myelin-specific T cell response in MS patients has shown parallels to EAE, this remains an area of intensive research because a number of questions remain. This review summarizes the important lessons from EAE, examines recent findings in MS, and discusses current concepts about how the disease process develops and which steps might be taken to modulate it.

Animals↗
PubMed1995

A practical approach to measuring an intravascular ultrasonographic imaging system beam pattern.

Characterizing beam patterns of miniature (1 to 3 mm diameter) catheter sonographic systems operating at 15 to 50 MHz is difficult and such information is often not provided by manufacturers. For investigators in the field, quantitative information describing catheters and their systems is important to properly understand measurements and images. A practical means of characterizing the system is described that can be assembled in most laboratories and used with existing catheter systems. The ultrasonic beam pattern from an intravascular sonographic transducer is characterized in three dimensions using images generated from a 150 microns diameter spherical target. Experiments are described in which the point spread function or beam pattern is mapped throughout the imaging system field-of-view. Using this approach, the beam pattern and resolutions for a commercial 1.18 mm diameter, 20 MHz intravascular catheter were measured.

Blood Vessels↗