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Biomedical subjects

J Martin

Publications and source records attributed to J Martin.

At least 163 records · Page 9Linked to original sources
PubMed2001

Targeted Disruption of the Myocilin Gene (Myoc) Suggests that Human Glaucoma-Causing Mutations Are Gain of Function.

Glaucoma is a heterogeneous eye disease and a major cause of blindness worldwide. Recently, primary open angle glaucoma (POAG)-associated mutations have been found in the trabecular meshwork inducible glucocorticoid response gene (TIGR), also known as the myocilin gene (MYOC), at the GLC1A locus on chromosome 1q21-q31. These mutations occurred in a subset of patients with juvenile- and adult-onset POAG and exhibited autosomal dominant inheritance. Ocular expression and its involvement in POAG suggest that TIGR/MYOC may have a role(s) in regulating intraocular pressure (IOP). Here, we report the generation and analysis of mice heterozygous and homozygous for a targeted null mutation in Myoc. Our study shows that Myoc mutant mice are both viable and fertile. Our in vivo findings further demonstrate that Myoc is not required for normal IOP or normal ocular morphology. The lack of a discernable phenotype in both Myoc-heterozygous and Myoc-null mice suggests that haploinsufficiency is not a critical mechanism for POAG in individuals with mutations in MYOC. Instead, disease-causing mutations in humans likely act by gain of function.

Animals↗
PubMed2001

Assembly of chaperonin complexes.

Chaperonins are a subclass of molecular chaperones that assist both the folding of newly synthesized proteins and the maintenance of proteins in a folded state during periods of stress. The best studied members of this family are the type I chaperonins, occurring in bacteria and evolutionarily derived organelles. Type II chaperonins occur in archaea and the eukaryotic cytosol. An intriguing question pertains to the mechanism by which chaperonins themselves are folded and assembled into functional oligomers. The available evidence for the assembly/disassembly of type I and II chaperonins points to a process that is highly cooperative and suggests a prominent role for nucleotides. Interestingly, the intracellular assembly of type I chaperonins appears to be a chaperone-dependent process itself and requires functional preformed chaperonin complexes.

Animals↗
PubMed2001

Improving cycling performance: how should we spend our time and money.

Cycling performance is dependent on physiological factors which influence mechanical power production and mechanical and environmental factors that affect power demand. The purpose of this review was to summarize these factors and to rank them in order of importance. We used a model by Martin et al. to express all performance changes as changes in 40 km time trial performance. We modelled the performance of riders with different ability ranging from novice to elite cyclists. Training is a first and most obvious way to improve power production and was predicted to have the potential to improve 40 km time trial performance by 1 to 10% (1 to 7 minutes). The model also predicts that altitude training per se can cause a further improvement of 23 to 34 seconds. Carbohydrate-electrolyte drinks may decrease 40 km time by 32 to 42 seconds. Relatively low doses of caffeine may improve 40 km time trial performance by 55 to 84 seconds. Another way of improving time trial performance is by reducing the power demand of riding at a certain velocity. Riding with hands on the brake hoods would improve aerodynamics and increase performance time by approximately 5 to 7 minutes and riding with hands on the handlebar drops would increase performance time by 2 to 3 minutes compared with a baseline position (elbows on time trail handle bars). Conversely, riding with a carefully optimised position could decrease performance time by 2 to 2.5 minutes. An aerodynamic frame saved the modelled riders 1:17 to 1:44 min:sec. Furthermore, compared with a conventional wheel set, an aerodynamic wheel set may improve time trial performance time by 60 to 82 seconds. From the analysis in this article it becomes clear that novice cyclists can benefit more from the suggested alterations in position, equipment, nutrition and training compared with elite cyclists. Training seems to be the most important factor, but sometimes large improvements can be made by relatively small changes in body position. More expensive options of performance improvement include altitude training and modifications of equipment (light and aerodynamic bicycle and wheels). Depending on the availability of time and financial resources cyclists have to make decisions about how to achieve their performance improvements. The data presented here may provide a guideline to help make such decisions.

Bicycling↗
PubMed2001

The power law distribution for walking-time intervals correlates with the ellipsoid-body in Drosophila.

The temporal properties of a variety of behavioral traits obey power law distributions, a property often referred to as fractal. We recently showed that the temporal pattern of locomotor activity of the fruitfly Drosophila melanogaster follows this distribution. Although an increasing number of such fractal patterns are being discovered, the brain areas and neuronal networks responsible remain unknown. In this study, we show that specifically blocking synapses established by neurons of the Drosophila ellipsoid-body, a substructure of the central complex in the brain, leads to a loss of the fractal properties in the temporal pattern. We conclude that the temporal fractal pattern of locomotor activity is regulated in the ellipsoid-body.

Animals↗
PubMed2001

Evaluation of flexible cloth electrodes for electrodermal activity recording.

BACKGROUND: Instrument selection for recording physiological data in flight studies requires careful attention to subject comfort and non-interference with aircrew activities. Several electrode types and recording sites may be used to examine electrodermal activity (EDA). Placement of electrodes on the foot minimizes interference with physical activity and reduces motion artifacts; however, use of conventional, hard-plastic-encased metal (PEM) electrodes within a flight boot can produce discomfort and pressure-induced artifacts. HYPOTHESIS: When applied with proper electrolyte gels, thin, flexible, silver-impregnated cloth electrodes should acquire EDA signals qualitatively similar to those acquired using conventional, PEM electrodes. METHODS: EDA responses evoked by light flashes, auditory stimuli and valsalva maneuvers were recorded with cloth and PEM electrodes simultaneously from both feet of 4 male subjects. Performance of cloth vs. PEM electrodes and variability of signals recorded with the same electrode type were examined by placing pairs of selected electrodes on each foot of the subjects. Placements were balanced with respect to age and handedness of the subject and the number of trials with each electrode type placed on the left or right foot. RESULTS: Qualitatively similar signals were recorded with cloth and PEM electrodes. Cloth electrodes showed more variability between electrodes of the same type. CONCLUSION: For EDA recording, cloth electrodes can perform at least as well as PEM electrodes, making it practical to take advantage of the cloth electrodes' flexibility and lower profile.

Adult↗
PubMed2001

Eplerenone (GD Searle & Co).

Eplerenone, an aldosterone receptor antagonist from Searle is being developed as a potential treatment for renal disease, congestive heart failure and hypertension. It is in phase III clinical trials 1312280], [353548]. Monsanto (now Pharmacia) expects to launch the compound in 2002 [370466]. Pharmacia anticipates filing for congestive heart failure in 2002 [374505]. A global phase III survival trial was initiated in the US and approximately 30 other countries in January 2000. The trial will evaluate whether eplerenone can reduce the rate of mortality in patients who have recently had a heart attack that resulted in a diagnosis of heart failure 13535481.

Animals↗
PubMed2001

Airway pressure release ventilation with a short release time in a child with acute respiratory distress syndrome.

Airway pressure release ventilation (APRV) allows ventilation and oxygenation to occur at lower peak and mean airway pressures than conventional positive pressure ventilation. The use of APRV in adults is an effective method of ventilation for patients with acute lung injury and acute respiratory distress syndrome. However, the use of APRV in children is less established. We report the use of APRV with a short release time of 0.2 s in a child with acute respiratory distress syndrome secondary to respiratory syncytial virus pneumonia.

Acute Disease↗
PubMed2001

Cochlear and middle ear implants: advances for the hearing impaired.

We have entered into an era of surgical audiology with cochlear and middle ear implants. With both devices there are distinct phases of patient management--patient selection, surgery, programming and rehabilitation. These phases and issues relating to the implants themselves are considered in this article.

Adult↗
PubMed2001

Risks of reintroduction of polio after eradication: the vaccine origin of an outbreak of type 3 poliomyelitis.

Sabin live-attenuated strains, which have proved to be the most effective tools for poliovirus eradication, could also be the source of reintroduction of polio epidemics after global eradication of wild poliomyelitis is achieved. There are still considerable gaps in our knowledge about the persistence of vaccine-derived viruses in the population and the mechanisms involved in poliovirus transmissibility, both of which are essential factors in assessing the risks posed by such strains and in designing effective strategies for the cessation of polio immunisation. In this report, we have examined virological and epidemiological aspects of an epidemic of poliomyelitis in 1968 in Poland that was shown to be associated with the use of the USOL-D-bac live-attenuated vaccine strain. Possible causes of the origin and progress of the outbreak included the pattern of virus excretion from vaccinees, mutations identified in epidemic viruses and the unique vaccination policies in Poland during the years preceding the epidemic.

Animals↗
PubMed2001

Reflux esophagitis and scleroderma.

Despite improvement in pharmacologic management, the reflux seen in patients who have scleroderma is significantly greater than the reflux seen in patients who have idiopathic reflux. Furthermore, even with significant symptom improvement, half of the patients who have scleroderma do not show complete healing of esophagitis, owing to residual gastroesophageal reflux. Acid and bile reflux monitoring and endoscopic control examination should be used routinely to provide quantitative information on reflux damage and control. These patients need repeated adjustment of maintenance drug doses.

Esophagitis, Peptic↗
PubMed2001

[Amniotic membrane graft in ocular surface disease. Prospective study with 31 cases].

INTRODUCTION: Amniotic membrane's unique combination of properties including the facilitation of migration of epithelial cells, the reinforcement of basal cellular adhesion and the encouragement of epithelial differentiation [6] together with its ability to modulate stromal scarring and its anti-inflammatory and anti-bacterial activity has led to its use in the treatment of ocular surface pathology as well as an adjunct to stem cell grafts of the corneal limbus [6-4]. We report a prospective study of 30 patients so treated. MATERIAL AND METHODS: We studied 31 eyes of 30 patients subjected to amniotic membrane grafts between September 1999 and May 2000. There were 25 men and 5 women with an average age of 60.1 (range 25-86) years who were followed for a mean of 7.7 (range 4-11) months. 5 groups (A to D) were observed: A: 6 eyes. Small chronic ulcers without limbal involvement. B: 4 eyes. Ulcers of at least 75% corneal area or occupying 75% of the limbus. C: 9 eyes. Corneal burns. D: 8 eyes. Painful bullous corneal dystrophies unresponsive to other treatment. E: 4 eyes. Symblepharons. Amniotic membrane was placed on the corneal lesion, epithelial surface externally [6, 15], trimmed and sutured with interrupted 10/0 nylon, removed at one month. In two patients (11, 12) inflamed conjunctiva was recessed and amnion sutured to the recessed margin. For the bullous dystrophies we removed all the corneal epithelium and either sutured the amnion to peri-limbal conjunctiva (4 eyes) or to the limbus (4 eyes). For the symblepharons the conjunctiva was dissected to reform the fornix which was lined with amniotic membrane, sutured with 8/0 vicryl. Patients were reviewed regularity. RESULTS: Group A: All healed within 15 days, in most with dissolution of the amnion over 2-3 months although some persisted, covered with corneal epithelium. An eye with a Descemetocoele and one with a microperforation both healed. Vision improved more than two lines in 4 of 6 eyes. Group B: 2 of 4 eyes healed, one despite detachment of the membrane after 15 days. One eye was salvaged by tarsorrhaphy over a fresh keratoplasty after perforation of a neuroparalytic ulcer on failure of three successive amnion grafts. The final cornea vascularised despite an amnion graft for a meta-herpetic ulcer. Group C: 2 of 9 eyes had limbal damage in one quadrant but 7 had vessels in at least three-quarters of the circumference. One (15) also had a limbal autograft. 3 of 9 eyes healed satisfactorily with more than 2/10 improvement in acuity in each case. 2 showed further neovascularisation despite surface healing. One old chemical burn healed satisfactorily but vascularisation remained 5 eyes failed to heal with lysis of the graft, the patient who had a limbal autograft developed a vascular pannus, and in 4 eyes neovascularisation progressed to cover the entire cornea. Group D: 3 eyes settled with loss of symptoms but in 5 the graft detached within 15 days. All eyes where the membrane had been sutured to the conjunctiva beyond the limbus failed whilst 3 of 4 in which it had been sutured anterior to the limbus succeeded, leaving a persistent whitish membrane under the epithelium. Group E: We were able to reconstruct the cul de sac in 3 out of 4 eyes. In one patient with recurrent pterygium good ocular movement was restored, previously limited by scarring. One with associated ocular surface damage from a thermal burn failed by scarring of the cul de sac a month after surgery. DISCUSSION: Our best results were in persistent trophic ulcers of the cornea (Groups A and B) with a success rate of 80%, comparable to those of others [49, 37, 38]. The ready availability of amniotic membrane in our facility makes amniotic membrane transplantation the main secondary treatment for such lesions, especially because of the visual improvement we obtained. Because we did not observe any improvement in corneal thickness after this treatment we advise its early use before significant stromal lysis. The technique was not sufficient to control the effect of corneal anaesthesia in two eyes [40] or in chemical burns suggesting that amniotic membrane alone is insufficient to promote corneal healing in the absence of limbal stem cells. Nevertheless, three eyes did benefit. It has been suggested [13] that the anti-apoptotic function of amnion may prevent stem cell loss in such eyes [42], thus it appears logical to offer an amniotic membrane graft first, before stem cell transplantation, which may entrain complications in the donor eye if autografted [43] or because of the rejection risk of an allograft. It may be that an amniotic membrane graft simply becomes a holding procedure allowing time to settle the eye so as to allow secondary procedures to address the underlying cause of further damage. Our treatment of bullous dystrophy only succeeded on confining the graft to within the limbus, 3 out of 4 eyes becoming comfortable. By contrast we found amniotic membrane helpful in reconstructing symblepharons in the absence of local inflammation. CONCLUSION: Amniotic membrane grafting is a simple and straightforward surgical technique which should form part of the therapeutic arsenal for the treatment of ocular surface disease. Indications for the technique need further clarification for it is evident that it cannot correct all secondary pathology associated with limbal destruction. It is certainly preferable to conjunctival advancement and has proved useful in the reconstruction of the cul-de-sac.

Adult↗
PubMed2000

Plasma concentrations of the enantiomers of methadone and therapeutic response in methadone maintenance treatment.

Methadone is a 50:50 mixture of two enantiomers and (R)-methadone accounts for the majority of its opioid effect. The aim of this study was to determine whether a blood concentration of (R)-methadone can be associated with therapeutic response in addict patients in methadone maintenance treatment. Trough plasma concentrations of (R)-, (S)- and (R,S)-methadone were measured in 180 patients in maintenance treatment. Therapeutic response was defined by the absence of illicit opiate or cocaine in urine samples collected during a 2-month period prior to blood sampling. A large interindividual variability of (R)-methadone concentration-to-dose-to-weight ratios was found (mean, S.D., median, range: 112, 54, 100, 19-316 ng x kg/ml x mg). With regard to the consumption of illicit opiate (but not of cocaine), a therapeutic response was associated with (R)- (at 250 ng/ml) and (R,S)-methadone (at 400 ng/ml) but not with (S)-methadone concentrations. A higher specificity was calculated for (R)- than for (R,S)-methadone, as the number of non-responders above this threshold divided by the total number of non-responders was higher for (R,S)-methadone (19%) than for (R)-methadone (7%). The results support the use of therapeutic drug monitoring of (R)-methadone in cases of continued intake of illicit opiates. Due to the variability of methadone concentration-to-dose-to-weight ratios, theoretical doses of racemic methadone could be as small as 55 mg/day and as large as 921 mg/day to produce a plasma (R)-methadone concentration of 250 ng/ml in a 70-kg patient. This demonstrates the importance of individualizing methadone treatment.

Adult↗
PubMed2000

Dysregulated expression of androgen-responsive and nonresponsive genes in the androgen-independent prostate cancer xenograft model CWR22-R1.

Treatment of metastatic prostate cancer with androgen-ablation often elicits dramatic tumor regressions, but the response is rarely complete, making clinical recurrence inevitable with time. To gain insight into therapy-related progression, changes in gene expression that occurred following androgen-deprivation of an androgen-dependent prostate tumor xenograft, CWR22, and the emergence of an androgen-independent tumor, CWR22-R, were monitored using microarray analysis. Androgen-deprivation resulted in growth arrest of CWR22 cells, as evidenced by decreased expression of genes encoding cell cycle components and basal cell metabolism, respiration and transcription, and the induced expression of putative negative regulatory genes that may act to sustain cells in a nonproliferative state. Evolution of androgen-independent growth and proliferation, represented by CWR22-R, was associated with a reentry into active cell cycle and the up-regulation of several genes that were expressed at low levels or absent in the androgen-dependent tumor. Androgen repletion to mice bearing androgen-independent CWR22-R tumors induced, augmented, or repressed the expression of a number of genes. Expression of two of these genes, the calcium-binding protein S100P and the FK-506-binding protein FKBP51, was decreased following androgen-deprivation, subsequently reexpressed in CWR22-R at levels comparable with CWR22, and elevated further upon treatment with androgens. The dysregulated behavior of these genes is analogous to other androgen-dependent genes, e.g., prostate-specific antigen and human kallikrein 2, which are commonly reexpressed in androgen-independent disease in the absence of androgens. Other androgen-responsive genes whose expression decreased during androgen-deprivation and whose expression remained decreased in CWR22 were also identified in CWR22-R. These results imply that evolution to androgen-independence is due, in part, to reactivation of the androgen-response pathway in the absence of androgens, but that this reactivation is probably incomplete.

Androgens↗
PubMed2000

High salt-induced conversion of Escherichia coli GroEL into a fully functional thermophilic chaperonin.

The GroE chaperonin system can adapt to and function at various environmental folding conditions. To examine chaperonin-assisted protein folding at high salt concentrations, we characterized Escherichia coli GroE chaperonin activity in 1.2 m ammonium sulfate. Our data are consistent with GroEL undergoing a conformational change at this salt concentration, characterized by elevated ATPase activity and increased exposure of hydrophobic surface, as indicated by increased binding of the fluorophore bis-(5, 5')-8-anilino-1-naphthalene sulfonic acid to the chaperonin. The presence of the salt results in increased substrate stringency and dependence on the full GroE system for release and productive folding of substrate proteins. Surprisingly, GroEL is fully functional as a thermophilic chaperonin in high concentrations of ammonium sulfate and is stable at temperatures up to 75 degrees C. At these extreme conditions, GroEL can suppress aggregation and mediate refolding of non-native proteins.

Adenosine Triphosphatases↗