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Biomedical subjects

R Martin

Publications and source records attributed to R Martin.

At least 397 records · Page 22Linked to original sources

Myelin basic protein-specific T-cell responses in identical twins discordant or concordant for multiple sclerosis.

Although multiple sclerosis (MS) is thought to be an autoimmune disease, the target antigen of the immune response is unknown. Both myelin basic protein (MBP) and proteolipid protein (PLP) have been considered candidate autoantigens. Because the immune response to either foreign or self antigens is influenced by the genetic background of the host, the importance of these candidate antigens has been difficult to establish in humans because of genetic diversity. To eliminate genetic differences in MS patients and healthy controls, we have studied the MBP-specific T-cell response in 6 sets of identical twins, 3 of which were concordant and 3 discordant for MS. A total of 638 short-term T-cell lines were established and characterized for MBP-specific proliferative and cytotoxic activity, fine specificity, and human leukocyte antigen (HLA) restriction. Similar frequencies of MBP-specific T cells were observed in affected and unaffected individuals. A slightly higher percentage of cytotoxic T-cell lines was found in affected individuals. For most of the cell lines, the restriction elements were the HLA class II antigens that have been reported previously to be associated with MS; no important differences with respect to HLA restriction were found between the patients and healthy individuals. The peptide epitopes of MBP that were recognized most frequently by the T-cell lines were those previously shown to be immunodominant. Differences in specificity were seen in some discordant twins indicating that, despite genetic identity, the MBP-specific T-cell repertoire may be shaped differently. These findings indicate that differences in frequency, peptide specificity, or HLA restriction are not sufficient to implicate MBP-specific T cells in the pathogenesis of MS. However, the T-cell response to MBP may still represent one necessary component with disease occurring when this response is combined with other host characteristics such as regulation of cytokine-, adhesion molecule-, or HLA-antigen expression in the nervous system or immunoregulatory mechanisms.

Adult↗

A functional basis for the association of HLA class II genes and susceptibility to multiple sclerosis: cellular immune responses to myelin basic protein in a multiplex family.

This study has examined the cellular response to myelin basic protein (MBP) in a multiplex family with multiple sclerosis (MS). A total of 81 MBP-specific T cell lines (TCLs) were derived from three affected siblings and four healthy siblings. No difference was observed in estimated precursor frequencies of MBP-specific TCLs or peptide specificity of TCLs when comparing affected and unaffected siblings. MBP-specific TCLs from affected siblings, however, were restricted to the DRw15/DQw6 allele more frequently than those from unaffected siblings (P < 0.02). These data suggest that restriction of autoantigen-specific T cells may be the functional basis for disease susceptibility related to HLA class II inheritance.

Adult↗

Selective bowel decontamination, nutritional therapy and bacterial translocation after burn injury.

We studied the influence of selective bowel decontamination (SBD) with neomycin, on bacterial translocation (BT) in rats treated with early post-burn parenteral nutrition (TPN) or enteral nutrition (TEN). Male Wistar rats were randomly assigned to receive either TPN (groups 1, 2) or an isonitrogenous, isocaloric polymeric diet (TEN, groups 3, 4) or a standard rat chow ad libitum (group 5), for 5 days after burn injury (30% b. s. area). In addition, groups 1 and 3 received a daily oral dose of neomycin (30 mg/kg) during the same period. At the end of the study, animals were killed and the mesenteric lymph nodes (MLN), liver (L) and spleen (S) were removed for microbiological cultures. The overall incidence of BT was MLN: 67%, L: 58% and S: 42% with a mortality rate of 12.2% In MLN and L, group 5 showed significantly less BT than groups 1 and 2 (30% vs 84%, p < 0.02) and groups 3 and 4 (38% vs 76%, p < 0.05), respectively. No differences were found between TPN and TEN groups. SBD (groups 1 and 3) resulted in a significantly lower mortality rate (26% vs 0%, p < 0.05) and BT in the liver (38% vs 100%, p < 0.001) than rats without antibiotic treatment (groups 2 and 4). It is concluded that early post-injury TPN or TEN promote BT to a greater extent than a standard chow. In addition, SBD with neomycin prevents mortality and BT after burn injury.

Journal Article↗

Within-session changes in sensory gating assessed by P50 evoked potentials in normal subjects.

1. The authors studied within-session changes in P50 suppression occurring in a group of 28 normal subjects. 2. A conditioning-testing paradigm was used with 120 pairs of 110 Db peak intensity clicks. Clicks were of 0.04 msec duration, 500 msec separation and delivered through headphones at 10 second intervals. 3. Mean P50 suppression ranged from 60.5% during the first 30 click pairs to -19.1% during the last 30 pairs, with an overall mean suppression of 25.4%. 4. The authors concluded that P50 suppression is a dynamic process in normal subjects, and that further work is necessary to elucidate the factors affecting P50 suppression.

Acoustic Stimulation↗

[Axillary plexus block by simultaneous blockade of several nerves. I. Influence of the volume of the anesthetic solution].

The influence of the volume of local anaesthetic solution on axillary blockade was investigated in a prospective randomized double-blind study including 120 patients presenting for upper limb surgery. A peripheral nerve stimulator was used to carry out the axillary block with a multiple injection technique. The musculocutaneous, radial, median and ulnar nerves were routinely stimulated. Four criteria were monitored: quality of sensory blockade, degree of motor blockade, time of onset and duration of anaesthesia. The patients were randomly allocated into two groups (n = 60 each). In the first, patients received 25 ml per m2 of body surface area of carbonated 1% lignocaine, 0.25% bupivacaine or a 1 to 1 mixture of both. Patients in the other group were given the same amount of local anaesthetic in half the volume, i.e. 12.5 ml.m-2 of carbonated 2% lignocaine, 0.5% bupivacaine or a 1 to 1 mixture of both these. Adrenaline (1 in 400,000) was added to half the anaesthetic solutions used in each group. The data demonstrated that, for a same amount of local anaesthetic, the larger volumes provided better quality sensory blockade than the smaller ones (p < 0.03). However, the volume of solution used affected neither the time of onset nor the duration of anaesthesia, nor the degree of motor blockade. It is concluded that, despite the use of a neurostimulator and simultaneous infiltration of several nerve trunks, the volume required to ensure a reliable degree of sensory block with the technique of axillary block is comprised between 40 and 50 ml (25 ml.m-2).

Adult↗

[Axillary plexus block by simultaneous blockade of several nerves. II. Evaluation of lidocaine-bupivacaine combination].

A mixture of carbonated lignocaine and bupivacaine for axillary blocks was assessed prospectively in a randomized double-blind study including 60 patients scheduled for upper limb surgery. A peripheral nerve stimulator was used to carry out the axillary block with a multiple injection technique. The musculocutaneous, radial, median and ulnar nerves were routinely stimulated. Four criteria were monitored: quality of sensory blockade, degree of motor blockade, time of onset and duration of anaesthesia. The patients were randomly assigned to three groups (n = 20 each). Patients received 25 ml per m2 of body surface area of either carbonated 1% lignocaine (group 1) or 0.25% bupivacaine (group 2) or a 1 to 1 mixture of both (group 3). Adrenaline (1 in 400,000) was added to half the anaesthetic solutions used in each group. The onset of anaesthesia was faster with the mixture (15 +/- 9 min) than will bupivacaine alone (23 +/- 14 min) (p < 0.02). It lasted longer in the mixture group (264 +/- 111 min) than in the lignocaine group (193 +/- 83 min). The longest duration was in the bupivacaine group (476 +/- 276 min) (p < 0.03). Adrenaline only affected significantly the duration of anaesthesia in the lignocaine group (252 min vs 135 min with and without adrenaline, respectively) (p < 0.03). In axillary blocks, the mixture of carbonated lignocaine and bupivacaine has a faster onset of action than bupivacaine alone, and a longer duration of action than lignocaine alone. Both agents provided a quality of sensory and motor blockade similar to that obtained with the mixture.

Adult↗

[Determination of steroid hormone receptors with the biochemical DCC method in endometrial cancer and tumor margin-endometrium relations to cellular changes and hormone level].

In endometrial carcinoma and the surrounding marginal endometrium from 48 postmenopausal patients, the concentrations and dissociation constants of steroid hormone receptors were studied by the dextran-coated charcoal method (DCC), parallel to ploidy and morphology of tumour cell nuclei, grading, and the hormonal status. The results show, that the proportion of receptor-positive tumours is decreased in an advanced stage of disease. The mean receptor concentrations correlate both with nuclei parameters and the morphological results and reflect the process of dedifferentiation in the tumour centre. The higher receptor concentrations, especially the estradiol receptor concentration observed in the marginal endometrium, and the increased estradiol level in serum, demonstrate a raised tendency to proliferation in this region and could support the hypothesis, that a higher receptor level in adenomatous-hyperplastic tissues participates in tumour genesis. In patients with an advanced stage of the disease, determination of both receptors can yield indications for a purposeful adjuvant hormone therapy (anti-estrogen and/or gestagen), in addition to providing an aid to prognosis.

Aged↗

Psychometric analysis in children with mental retardation due to perinatal hypoxia treated with fibroblast growth factor (FGF) and showing improvement in mental development.

Basic fibroblast growth factor (bFGF) has shown a neurotrophic effect in the neurons of several CNS areas. In vivo, it contributes to restore neurochemical and morphological deficits in different rodent models of brain damage, including rats with brain damage induced by hypoxia/ischemia when FGF was intramuscularly (i.m.) administered. Toxicological and immunological studies performed in rats, mice and volunteers showed no evidence of side-effects. Bovine FGF was i.m. administered in children with mental retardation caused by perinatal hypoxia, aged 1-15 years, at dosages of 0.4 or 0.28 microgram kg-1, once or twice a month, over 7-12 months. Group A [n = 12; 6 treated (T), 6 controls (Ct)], group B (n = 16; 8 T, 8 Ct) and group C (n = 67; 45 T, 22 Ct) were evaluated with the P. A. R. scale, the WISC-RM and the Gesell scale, respectively. Development increased significantly in treated children from groups A (P < 0.02) and C (P < 0.001), and IQ rose by more than 10 points (P < 0.001) in group B patients.

Adolescent↗

Viability and isolation of marine bacteria by dilution culture: theory, procedures, and initial results.

Dilution culture, a method for growing the typical small bacteria from natural aquatic assemblages, has been developed. Each of 11 experimental trials of the technique was successful. Populations are measured, diluted to a small and known number of cells, inoculated into unamended sterilized seawater, and examined three times for the presence of 10 or more cells per ml over a 9-week interval. Mean viability for assemblage members is obtained from the frequency of growth, and many of the cultures produced are pure. Statistical formulations for determining viability and the frequency of pure culture production are derived. Formulations for associated errors are derived as well. Computer simulations of experiments agreed with computed values within the expected error, which verified the formulations. These led to strategies for optimizing viability determinations and pure culture production. Viabilities were usually between 2 and 60% and decreased with >5 mg of amino acids per liter as carbon. In view of difficulties in growing marine oligobacteria, these high values are noteworthy. Significant differences in population characteristics during growth, observed by high-resolution flow cytometry, suggested substantial population diversity. Growth of total populations as well as of cytometry-resolved subpopulations sometimes were truncated at levels of near 10 cells per ml, showing that viable cells could escape detection. Viability is therefore defined as the ability to grow to that population; true viabilities could be even higher. Doubling times, based on whole populations as well as individual subpopulations, were in the 1-day to 1-week range. Data were examined for changes in viability with dilution suggesting cell-cell interactions, but none could be confirmed. The frequency of pure culture production can be adjusted by inoculum size if the viability is known. These apparently pure cultures produced retained the size and apparent DNA-content characteristic of the bulk of the organisms in the parent seawater. Three cultures are now available, two of which have been carried for 3 years. The method is thus seen as a useful step for improving our understanding of typical aquatic organisms.

Journal Article↗

Influence of respiration on heart rate and blood pressure fluctuations.

The dynamics of the respiratory and cardiovascular systems were studied by continuously slowing respiration from 0.46 to 0.05 Hz. The time-frequency distribution and global spectral analysis were used to assess the R-R interval (R-R) and the systolic and diastolic blood pressure fluctuations in 16 healthy subjects. During rest, the nonrespiratory-to-respiratory frequency ratios were not affected by occasional slow breathing, whereas the low- (0.01-0.15 Hz) to high- (0.15-0.3 Hz) frequency indexes for blood pressure were increased (P < 0.05). The respiratory fluctuations in R-R and the systolic and diastolic pressures were paced over the 0.46- to 0.05-Hz range. As respiration slowed to 0.07-0.09 Hz, the frequency content of the respiration and cardiovascular variables increased sharply and nonlinearly to a maximum that exceeded values at higher frequencies (P < 0.001). The nonrespiratory frequency content remained stable in the 0.01- to 0.05-Hz range and did not significantly differ from that at rest. In contrast, the nonstable 0.05- to 0.1-Hz component was suppressed. A slow 0.012- to 0.017-Hz rhythm modulated respiration and hemodynamic fluctuations at both respiratory and nonrespiratory frequencies. The study indicated that respiration input should be considered in the interpretation of global spectra. Furthermore the time-frequency distributions demonstrated that a close nonlinear coupling exists between the respiratory and cardiovascular systems.

Adult↗

High-resolution imaging of protein phosphorylation in squid axons and synapse by electron energy loss spectroscopy.

We demonstrate that clusters of phosphorus atoms can be detected in energy loss spectroscopic images (ESI) of cytoskeletal proteins of squid axons. In series of images taken at four energy windows below and three windows above the phosphorus P-L2,3 ionization edge, signal-to-background intensity differences were analyzed by videodensitometry. A distinct increase of relative intensities was recorded above the phosphorus edge in neurofilaments of the peripheral giant axon and in those of the presynaptic terminal. A high level of neurofilament phosphorylation in the peripheral axon supports previous biochemical and immunochemical results, but our finding of phosphorylated neurofilaments in the presynaptic axon conflicts with these studies. Our method may be advantageous for analysis with high elemental and spatial resolution of the phosphorylation state of cytoskeletal protein molecules in situ.

Animals↗

A systematic approach to spinal reconstruction after anterior decompression for neoplastic disease of the thoracic and lumbar spine.

The anterior approach to the thoracic and lumbar spine for neoplastic disease is now a well-accepted procedure, with results, for the most part, superior to those achieved with laminectomy. However, the specific indications for anterior decompression and the selection of reconstruction techniques based on the location and extent of bony destruction have received surprisingly little attention. The authors report their experience with the operative management of 33 patients with benign and malignant tumors of the thoracic and lumbar spine, using the anterior transthoracic or retroperitoneal approach. The role of stabilization and the relative indications for anterior or posterior instrumentation are emphasized. The mean age of patients was 58 years. Twenty-three patients were male. Five patients had benign tumors, and the remainder had a variety of metastatic lesions. Twenty-nine patients had lower extremity motor deficits, although 25 were ambulatory preoperatively. Thirty-seven noncontiguous resections were performed in 33 patients. In 13 patients, the resected vertebral body was replaced with acrylic or bone without instrumentation; in 18, the acrylic was supplemented with anterior instrumentation; and in 6, both anterior and posterior instrumentation were used. Above T11, vertebral reconstruction techniques were used to restore stability after decompression. Between T11 and L4, anterior instrumentation was used to supplement vertebral reconstruction in all patients. Supplemental posterior instrumentation was used for three-column involvement. Motor function was stabilized or improved in 94% of patients, and 88% of patients were ambulatory postoperatively. Of 28 patients with malignant disease, 23 died after a mean survival of 10.2 months (range, 2-51 mo) and 5 are alive a mean of 34.4 months since their operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Safety testing of a new electronic toothbrush.

While there have been major advances in understanding the causes and treatments of the inflammatory periodontal diseases in the past decade, there is still high reliance on the patient to prevent progression of disease through daily oral hygiene, primarily toothbrushing and flossing. A new electronic toothbrush, which produces mild fluid cavitation as well as rapid fluid streaming, has been developed and has shown promise in the ease and efficacy with which it removes plaque. In order to determine the safety of frequent and prolonged use of this device, the gingival tissues of 6 mongrel dogs were exposed to excessively long daily exposures to this toothbrush for up to 2 months. Each quadrant of each dog's mouth was randomly assigned a different treatment: no brushing, manual brush 1.0 minute, electronic brush 1.0 minute, or electronic brush 7.5 minutes. The dogs were examined weekly by a periodontist who was blinded to the treatments. Plaque scores and bleeding on probing scores were calculated, and possible gingival irritation was monitored carefully. At the end of the trial gingival biopsies taken from all the test areas. These were processed for conventional histopathologic evaluation and examined by an oral pathologist who was also blinded as to the treatments. The results showed that brushing a single posterior segment of teeth for 7.5 minutes daily for 2 months with the electronic brush did not result in any clinically or histologically evident damage to the gingiva. Rather, the areas so treated showed excellent health as determined by both clinical and histologic criteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

T helper 1 (Th1) functional phenotype of human myelin basic protein-specific T lymphocytes.

Multiple sclerosis (MS) is widely accepted as an autoimmune disease with myelin basic protein (MBP) a candidate autoantigen. In the current report, human T cell lines specific for an immunodominant region of MBP were shown to have a functional phenotype similar to T helper 1 (Th1) inflammatory cells of the mouse on the basis of their antigen-specific cytotoxic activity and production of interferon-gamma and lymphotoxin/tumor necrosis factor-alpha, but not interleukin-4. In experimental allergic encephalomyelitis (EAE), a proposed animal model for MS, MBP-specific T cell lines which mediate disease are of the Th1 subtype. Thus, MBP-specific T cells in humans exist which are phenotypically similar to MBP-specific encephalitogenic T cells in murine EAE.

Adult↗