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Biomedical subjects

C Martin

Publications and source records attributed to C Martin.

At least 487 records · Page 27Linked to original sources
PubMed1996

Enhanced response of macrophages to CSF-1 in autoimmune mice: a gene transfer strategy.

Mice with the MRL background have a genetic propensity for autoimmune lupus nephritis. The lpr mutation on the MRL, but not the C3H background, induces rapid and fatal renal injury in which macrophages (M phi) are prominent. We previously established that CSF-1 accompanies M phi accumulation in the kidney of MRL-lpr mice. Furthermore, CSF-1 introduced into the kidney incites renal injury in mice with the lpr mutation, but not congenic strains. Notably, CSF-1 induces more severe tissue injury in MRL-lpr than in C3H-lpr mice. We hypothesized that M phi from the MRL background respond more readily to CSF-1 than normal strains. We establish herein the following: 1) glomerular M phi and bone marrow M phi (BMM phi) from MRL-lpr mice proliferate similarly to CSF-1; 2) MRL BMM phi proliferate more vigorously to CSF-1 than normal strains (C3H, BALB/c) or another strain with lpr (C3H-lpr); and 3) modulation of CSF-1 receptor expression by CSF-1 is more rapid in MRL than C3H BMM phi. We used a gene transfer strategy to deliver CSF-1 into the kidney to evaluate M phi response to CSF-1. We genetically modified tubular epithelial cells to produce CSF-1 (CSF-1-TECs) and placed these cells with BMM phi under the renal capsule. CSF-1-TEC + BMM phi caused a greater accumulation of M phi in the implant site and interstitium of MRL +/+ than C3H +/+ mice. Furthermore, CSF-1-TEC + BMM phi caused a lesion consisting of M phi in MRL +/+ mice, extending from the implant into the adjacent cortex. We suggest that the response of MRL M phi to CSF-1 is responsible for the notable accumulation of M phi in the MRL-lpr kidney.

Animals↗
PubMed1996

Association study between schizophrenia and monoamine oxidase A and B DNA polymorphisms.

Monoamine oxidases (MAO) A and B, which are encoded by two distinct genes located on the human X chromosome, are both involved in the oxidative metabolism of dopamine. Decreased levels of platelet MAO-B activity has been reported in patients with schizophrenia and genetic variation in MAO activity had been proposed as a significant factor in the etiology of this disease. We carried out an association study using two intragenic polymorphisms within the MAO-A and MAO-B genes in 110 schizophrenic patients and 87 control subjects. For each polymorphic marker, no significant difference in allelic frequencies was observed between patients and controls. Nevertheless, a trend toward an association between allele 1 of the MAO-B gene and paranoid schizophrenia was found. Our results do not support the hypothesis that inherited variants of MAO genes might play a major role in a genetic predisposition to schizophrenia. Since several previous reports found a low MAO-B platelet activity in patients with paranoid schizophrenia, the identification of polymorphisms related to enzyme activity would be useful.

Adolescent↗
PubMed1996

Time-Resolved Simultaneous SAXS/WAXS of the Drawing of Polyethylene at the Daresbury SRS.

A system has been developed which represents a significant advance in the quality and extent of small- and wide-angle X-ray scattering data (SAXS and WAXS) that can be recorded simultaneously with strain data during the drawing and annealing of polymer materials. WAXS data are recorded using a Photonic Science charge-coupled-device area detector and SAXS data using a gas-filled multiwire area detector. Strain data, for the region of the specimen from which the SAXS/WAXS data are collected, are calculated from an accurately synchronized continuously recorded video image of the specimen. The system allows X-ray and video image data to be collected as a series of frames with essentially no ;dead-time' between frames. The data are fully two-dimensional and can be collected for a wide range of d spacings. The use of this system to investigate the stress-induced orientation and phase changes during the drawing of a range of grades of commercially available polyethylene is described.

Journal Article↗
PubMed1996

Creation of a District Diabetes Register using the DIALOG system.

A District Diabetes Register has been created using the Family Health Services Computer Unit system, DIALOG, linked to the Family Health Services Authority (FHSA) population register. Initial informal discussions between the Diabetes Centre, Public Health, and the FHSA led to a formal proposal being accepted by the Local Diabetes Services Advisory Group to pilot the DIALOG software. Following installation of DIALOG on a separate computer, electronically linked to the main FHSA system, the register was compiled. This was approached in three ways. The existing Diabetes Centre Register was downloaded into DIALOG and patients matched with the FHSA register. A 'diabetes roadshow' was mounted, with Postgraduate Education Allowance approval, to individually visit every general practice in the district to explain the aims and objectives of creating a diabetes register and to enlist the support of these practices. Where practices already held their own diabetes register this was similarly transferred, if not, assistance was provided to identify their patients with diabetes. All patients were notified in writing that their names were being placed upon a diabetes register and that clinical data would be held against their entry. This notification included an opportunity to opt out. Additionally, a self registrations scheme was introduced whereby all retail pharmacists dispensing any diabetes related product and all optometrists seeing a person with diabetes, gave the patient a leaflet, describing the register and its purposes and inviting them to register themselves. A 'Data Ownership Committee' was established to control the use and interpretation of all clinical data held upon the register. The process of diabetes annual review is now being prompted across both primary and secondary care and clinical data is being returned to the register.

Diabetes Mellitus↗
PubMed1996

Characteristics of voluntary visual sampling of the environment for safe locomotion over different terrains.

The characteristics of visual sampling required for successful locomotion over various terrains is the focus of this work. In the first experiment we directly address the role of continuous visual monitoring of the environment in guiding locomotion by allowing the subjects to choose when and where to take a visual sample of the terrain and examine the effects of different terrains on characteristics of visual sampling. Young subjects walked over travel paths of varying difficulties while wearing opaque liquid crystal eyeglasses and pressed a hand-held switch to make the glasses transparent when they needed to sample the environment. Travel time and visual sampling characteristics were recorded. Results show that intermittent sampling (less than 50%) of the environment is adequate for safe locomotion, even over a novel travel path. The frequency, duration and timing of visual samples are dependent on terrain characteristics. Visual sampling of the environment is unaffected by preview restriction of the travel path and is increased when specific foot placement is required and there is a potential hazard in the travel path. In the second experiment we dissociated steering control and obstacle avoidance from specific foot placement and examined visual sampling demands prior to the initiation of the swing phase and during the swing phase. The results show that steering control and obstacle avoidance do influence the visual sampling time, which is scaled to the magnitude of change. Vision was used in a feedforward control mode to plan for and initiate appropriate changes in the swing limb trajectory: its use during the swing phase to provide on-line control was minimal.

Adult↗
PubMed1996

Stereoselective pharmacokinetics of mefloquine in young children.

OBJECTIVE: the stereospecificity of mefloquine pharmacokinetics in children has been investigated. PATIENTS: Twelve children aged 6 to 24 months were treated for uncomplicated falciparum malaria with a single oral dose of 25 mg.kg-1 racemic mefloquine in combination with sulfadoxine and pyrimethamine. METHODS: concentrations of mefloquine enantiomers were determined using a coupled achiral-chiral chromatographic system. Pharmacokinetic parameters were calculated using model-independent analysis. RESULTS: Maximum plasma concentrations, areas under the curve and apparent plasma elimination half-lives were higher for the (-) enantiomer than its antipode. In contrast, the apparent volume of distribution (V/f) and total clearance (Cl/f) values were higher for the (+) enantiomer. CONCLUSION: the stereoselectivity of mefloquine pharmacokinetics is similar to that observed in adults.

Antimalarials↗
PubMed1996

Dose-related effects of low dose aspirin on hemostasis parameters and prostacyclin/thromboxane ratios in late pregnancy.

BACKGROUND: The purpose of this study was to determine which low dose of low dose aspirin (LDA) optimized the urinary prostacyclin (PGI2)/thromboxane (TXA2) ratio and minimized evidence of platelet aggregation during normal late pregnancy. METHODS: Twelve women with uncomplicated singleton pregnancies between 28 and 34 weeks gestation participated in a randomized blinded study. Blood samples for salicylate levels were obtained pretreatment, 4 hours and 7 days after administration of placebo, 20mg, 40mg or 80mg of aspirin. Twenty-four hour urine specimens collected at the same intervals were assayed for PGI2 and TXA2 metabolites. In addition, bleeding time and platelet aggregation studies were performed prior to and after 7 days of LDA or placebo. RESULTS: A dose-related increase in bleeding time occurred with 40 mg and 80 mg of LDA, but not with the 20 mg dose or placebo. Platelet aggregation studies changed progressively from a normal baseline to abnormal with an increasing dose of LDA. The PGI2/TXA2 ratio increased with aspirin doses as low as 20mg, with a decrease in TXA2 metabolites but not in PGI2 metabolites. Serum salicylate was not detectable in any sample from any patient. CONCLUSION: There are dose-related changes in platelet aggregation and bleeding times with progressively increasing doses of LDA. A lower dose of LDA, such as 20-40 mg per day, may be as efficacious as higher doses in the prophylaxis of pre-eclampsia in high risk populations.

Adolescent↗
PubMed1996

The serotonin transporter from human brain: purification and partial characterization.

The serotonin (5-HT) transporter from human striatum was solubilized by digitonin and purified by affinity chromatography. The native protein-detergent complex had a molecular mass of 205 kDa, as estimated by gel-exclusion chromatography of the eluates obtained from affinity chromatography. The purified 5-HT transporter migrated as a single band of 67 kDa in SDS-PAGE. To clarify the spatial relationships between the binding sites of the tricyclic antidepressants, as [3H]-imipramine, and of the selective serotonin reuptake inhibitors, as [3H]-paroxetine, on the 5'HT transporter, both radioligands were used to label it in the purification steps. [3H]-paroxetine bound with the same affinity to a single high-affinity site on both membrane and purified preparations. [3H]-imipramine labeled a high- and a low-affinity site on parent membranes, whereas it bound to a single high-affinity site on the purified extract. Tricyclic antidepressants, selective serotonin reuptake inhibitors and 5-HT itself displaced [3H]-paroxetine and [3H-]imipramine from their high-affinity binding sites on both the membrane-bound and the purified 5-HT transporter in a monophasic fashion with Hill coefficients close to unity. Furthermore, both [3H]-paroxetine and [3H]-imipramine displayed a similar maximum binding capacity on an identical protein of 205 kDa. Our results suggest overlapping binding sites for tricyclic antidepressants, selective serotonin reuptake inhibitors and 5-HT on the 5-HT transporter.

Antidepressive Agents, Tricyclic↗
PubMed1996

Molecular dynamics study of early picosecond events in the bacteriorhodopsin photocycle: dielectric response, vibrational cooling and the J, K intermediates.

Molecular dynamics simulations have been carried out to study the J625 and K590 intermediates of bacteriorhodopsin's (bRs) photocycle starting from a refined structure of bR568. The coupling between the electronic states of retinal and the protein matrix is characterized by the energy difference delta E(t) between the excited state and the ground state to which the protein contributes through the Coulomb interaction. Our simulations indicate that the J625 intermediate is related to a polarization of the protein matrix due to the brief (200 fs) change of retinal's charge distribution in going to the excited state and back to the ground state, and that the rise time of the K590 intermediate is determined by vibrational cooling of retinal.

Bacteriorhodopsins↗
PubMed1996

Acidity near eroding polylactide-polyglycolide in vitro and in vivo in rabbit tibial bone chambers.

Eroding poly(DL-lactide-co-glycolide)(PDLLG) washers were observed chronically in vitro and in vivo following loading in a bone chamber tibial implant (BCI). Images were recorded using intravital microscopy of the implanted rabbit and direct pH measurements were obtained of the tissue in the bone chamber using a combination probe-reference microelectrode. While statistically significant pH differences were found between the control (unloaded) and experimental (PDLLG-bearing) BCIs, they were only of the order of 0.2 pH units. This value proved to be physiologically insignificant as no statistically significant difference in bone defect healing, as indicated by angiogenesis, was detected. It was shown that the measured small pH changes during PDLLG washers erosion would result whether the buffer was phosphate-buffered saline replaced weekly or interstitial fluid subject to vascular exchanges.

Animals↗
PubMed1996

Functional-lesion investigation of developmental stuttering with positron emission tomography.

Positron emission tomographic (PET) H2(15)O measurements of resting-state regional cerebral blood flow (CBF) were obtained in 29 right-handed men, 10 of whom stuttered and 19 of whom did not. PET images were analyzed by sampling 74 regions of interest (ROIs), 37 per hemisphere. ROI placement was guided both physiologically and anatomically. Physiological ROI placement was based on speech motor activations. Anatomical ROIs were positioned by reference to a stereotactic, neurosurgical atlas with positions confirmed and finely adjusted by co-registered magnetic-resonance images (MRIs). For all subjects, PET and MR images were normal to visual inspection. Highly significant (p < 0.0001) between-region and between-hemisphere effects were found for both groups, as have been previously reported for normal subjects, but no significant between-group differences were found for any regional CBF values. Analysis by a laterality index found a weakly significant between-groups effect (p = 0.04) that was isolated to five regions, four of which are implicated in speech or hearing. However, these regional laterality effects showed no consistent directionality, nor did these regions have absolute differences in regional blood flow between groups. Present findings do not support recent suggestions that developmental stuttering is associated with abnormalities of brain blood flow at rest. Rather, our findings indicate an essentially normal functional brain terrain with a small number of minor differences in hemispheric symmetry.

Adult↗
PubMed1996

The clp (CS31A) operon is negatively controlled by Lrp, ClpB, and L-alanine at the transcriptional level.

Biosynthesis of the Escherichia coli CS31A surface antigen was subject to phase-variation control and repressed by L-alanine. Nucleotide sequence analysis of the clp operon, encoding the biosynthesis of CS31A, revealed the presence of a regulatory gene, clpB. The amino acid sequence of the regulatory protein ClpB showed similarity to the primary structure of PapB, FaeB and AfaA, involved in the regulation of expression of Pap, K88, and Afa-3 fimbriae, respectively. The clp regulatory region contained two deoxyadenosine methylase sites (GATC-I and GATC-II). The leucine-responsive regulatory protein (Lrp) was required for specific methylation inhibition of the GATC-II site. The activity of the clp promoter was monitored in a clp-lacZYA single-copy fusion. The cloned DNA used in this study did not contain a related papl gene. In these conditions, we showed, as expected, that phase variation did not occur. However, transcription of the clp operon was negatively controlled by ClpB and Lrp, and was maximal in the absence of Dam methylase. In the presence of AfaF, a Papl equivalent, the phase-variation control was restored. We concluded that two regulatory mechanisms were superimposed to control the clp expression. Phase variation, mediated by Lrp and a Papl equivalent, controlled the number of cells producing CS31A in a single colony. The second mechanism, described in this report, was mediated by ClpB and Lrp and controls the level of CS31A produced by a single cell. Furthermore, we showed that L-alanine reduced, by about twofold, the clp promoter activity independently of a Papl equivalent, ClpB, Lrp or Dam methylase. In addition, the presence of L-alanine prevented the phase-variation control mediated by AfaF.

Alanine↗
PubMed1996

Influence of barley and buffer supplements on quantitative aspects of ruminal fiber digestion of cows.

Four Jersey cows, fitted with ruminal and duodenal cannulas, were used to assess the specific effects of changes in ruminal pH that were induced by barley addition to a hay diet on ruminal fiber digestion. Cows received successively 100% unchopped cocksfoot hay (diet H), 65% hay and 35% pelleted ground barley (diet HB), and HB plus a continuous intraruminal infusion of bicarbonate salt solution (diet HBB). Cows were limit-fed once daily at 7 kg of DM day-1. The ruminal fractional passage rate of the liquid and hay was respectively estimated from a single administration of Cr-EDTA and Eu labeled on hay fiber. Duodenal fiber flow was estimated both by the double marker method (Yb-acetate/Cr-EDTA) and by multiplying the fractional passage rate of Eu-labeled hay by ruminal pool size. Barley supplement decreased ruminal NDF and ADF digestion compared with diet H, but passage rates of the solid and fluid fractions in the rumen were not affected. The depressive effect of barley supplement on in situ degradability of hay NDF and ADF decreased the degradation rates and increased the 72-h undegradable fraction. Compared with diet HB, ruminal NDF and ADF digestion was improved with buffer supplementation but was less than that of diet H, even though ruminal pH was similar to that of diet H. Passage rates of the fluid and particle fractions were depressed and unaffected, respectively, with buffer addition. Higher in situ degradability of hay with the buffer supplement resulted in an increase in the 72-h undegradable fraction, but the fractional degradation rate was unaffected.

Animals↗
PubMed1996

Local antibiotic prophylaxis in surgery.

The perioperative use of antibiotics is an established and accepted technique for the prevention of postoperative infection. Intravenous administration often is preferred, and intramuscular administration is possible, although it has certain drawbacks. This article examines a variety of other routes of administration for delivering antibiotics locally to the surgical site. These techniques merit further study in prospectively randomized trials.

Antibiotic Prophylaxis↗
PubMed1996

5-Fluorouracil versus 5-fluorouracil plus alpha-interferon as treatment of metastatic colorectal carcinoma. A randomized study.

BACKGROUND: In 1989, S. Wadler reported very promising results (76% response rate) with a combination of 5-fluorouracil (5-FU) plus alpha-2a interferon (IFN) in the treatment of metastatic colorectal carcinoma (MCRC). In vitro, there are several potential explanations for synergism between the two agents. We therefore decided in 1989 to start a randomized study comparing 5-FU alone with 5-FU plus IFN. PATIENTS AND METHODS: 105 non-pretreated patients with measurable metastatic colorectal carcinoma entered into this study. The patients were randomly allocated either in arm A (n = 49) with 5-FU: 750 mg/m2 i.v. CI d1-d5 followed by 750 mg/m2 i.v. bolus once a week, or in arm B (n = 56) with 5-FU as in arm A plus IFN 9 x 10(6) IU sub-cutaneously three times a week. RESULTS: After two months of treatment we observed 1 CR and 2 PR in arm A (response rate 6.1%), 3 CR and 8 PR in arm B (response rate 19.6%), i.e., a significant difference (P = 0.05). Event-free survival was significantly higher in arm B (6 months) than in arm A (2 months) (P < 0.01), while median survival was slightly higher in arm B (12 months) than in arm A (10 months) (P < 0.05). For overall survival the difference was not significant after adjustment on center treatment and baseline Karnofsky status (P = 0.13). Toxicity was also greater in arm B. Sixteen percent of patients in arm A and 36% in arm B experienced certain grade 3-4 side effects (P < 0.05). CONCLUSION: 5-FU plus IFN is more effective than 5-FU alone in terms of response rate, event free survival but not of overall survival. 5-FU plus IFN is more toxic. As IFN has no demonstrated efficacy in MCRC as a single agent, this study suggests that IFN is acting as a 5-FU modulatory agent. The response rate observed (19.6%) is similar to the results obtained elsewhere with 5-FU plus leucovorin.

Adult↗
PubMed1996

Pathological, immunological, and molecular features of Hodgkin's disease associated with HIV infection. Comparison with ordinary hodgkin's disease.

The aim of the present study was to analyze in a series of 24 HIV-positive Hodgkin's disease (HD) patients the morphological and immunological features, the presence of rearrangements in the immunoglobulin heavy chain (IgH) gene, expression of the Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1), and the existence of deletions in the intracytoplasmic domain of the LMP-1 gene. The results obtained were compared with those from a parallel series of 56 patients with ordinary HD. Briefly, comparison of the two series showed a predominance of unfavorable histological subtypes in HIV-positive HD patients. The mixed cellularity subtype was more frequent in HIV-positive than in HIV-negative HD patients: the difference in percentage was statistically significant (p = 0.04). Neoplastic cell-rich cases were significantly more frequent (p = 0.40) in HIV patients (59%) than in ordinary HD patients (34%). In 25% of HIV-infected and in 14% of ordinary HD patients, the neoplastic cells were CD20+, a difference that was not statistically representative. Clonal IgH rearrangements were detected in 33% of HIV-infected patients and in 23% of ordinary HD patients, a nonsignificant difference. LMP-1 expression was detected in 100% of HIV-positive patients and in 57% of ordinary HD patients (p = 0.004). A 30-base-pair deletion in the carboxy-terminal domain of the LMP-1 gene was found in 16 of 18 HIV-infected patients (89%), whereas it was identified in only 8 of 25 ordinary HD patients (32%) (p = 0.008). In conclusion, HD in HIV-infected patients as compared with HD in HIV-negative individuals is associated with morphological features of aggressivity, with a higher frequency of neoplastic cells, and with constant LMP-1 expression. The fact that LMP-1 is expressed in all HIV-infected patients suggests that EBV plays an etiological role in the pathogenesis of HIV-associated HD. Furthermore, the presence of EBV strains carrying deletions near the 3' end of the LMP-1 gene in the majority of cases may be related with the morphological and clinical aggressivity of HD in immunocompromised patients.

Adult↗
PubMed1996

The Mycobacterium tuberculosis purine biosynthetic pathway: isolation and characterization of the purC and purL genes.

Genes from the Mycobacterium tuberculosis purine biosynthetic pathway were identified using purine auxotrophic mutants of Mycobacterium smegmatis obtained by Tn611 transposon mutagenesis. Two approaches were followed in parallel. The first consisted of the complementation of the M. smegmatis purine auxotrophs using a M. tuberculosis H37Rv shuttle cosmid library. In the second approach, specific probes corresponding to the regions adjacent to the insertion sites of Tn611 in the M. smegmatis genome were used to screen a M. tuberculosis plasmid library by colony hybridization for inserts carrying homologous DNA fragments. Nucleotide sequence analysis of two M. tuberculosis genes isolated by these methods revealed high similarities with purC and purL genes from other bacterial and fungal sources. Transcriptional start sites were mapped for both genes, which revealed similar-10 boxes but with a higher GC content than the Escherichia coli sigma 70 consensus.

Amino Acid Sequence↗