Optical Methods for Brain Tumor Detection: A Systematic Review.

Background: In brain tumor surgery, maximal tumor resection is typically desired. This is complicated by infiltrative tumor cells which cannot be visually distinguished from healthy brain tissue. Optical methods are an emerging field that can potentially revolutionize brain tumor surgery through intraoperative differentiation between healthy and tumor tissues. Methods: This study aimed to systematically explore and summarize the existing literature on the use of Raman Spectroscopy (RS), Hyperspectral Imaging (HSI), Optical Coherence Tomography (OCT), and Diffuse Reflectance Spectroscopy (DRS) for brain tumor detection. MEDLINE, Embase, and Web of Science were searched for studies evaluating the accuracy of these systems for brain tumor detection. Outcome measures included accuracy, sensitivity, and specificity. Results: In total, 44 studies were included, covering a range of tumor types and technologies. Accuracy metrics in the studies ranged between 54 and 100% for RS, 69 and 99% for HSI, 82 and 99% for OCT, and 42 and 100% for DRS. Conclusions: This review provides insightful evidence on the use of optical methods in distinguishing tumor from healthy brain tissue.

Fiber-Optic Pedicle Probes to Advance Spine Surgery through Diffuse Reflectance Spectroscopy.

Diffuse Reflectance Spectroscopy (DRS) can provide tissue feedback for pedicle screw placement in spine surgery, yet the integration of fiber optics into the tip of the pedicle probe, a device used to pierce through bone, is challenging, since the optical probing depth and signal-to-noise ratio (SNR) are affected negatively compared to those of a blunt DRS probe. Through Monte Carlo simulations and optical phantom experiments, we show how differences in the shape of the instrument tip influence the acquired spectrum. Our findings demonstrate that a single bevel with an angle of 30∘ offers a solution to anticipate cortical breaches during pedicle screw placement. Compared to a blunt probe, the optical probing depth and SNR of a cone tip are reduced by 50%. The single bevel tip excels with 75% of the optical probing depth and a SNR remaining at approximately ⅔, facilitating the construction of a surgical instrument with integrated DRS.

Diffuse reflectance spectroscopy of the spine: improved breach detection with angulated fibers.

Accuracy in spinal fusion varies greatly depending on the experience of the physician. Real-time tissue feedback with diffuse reflectance spectroscopy has been shown to provide cortical breach detection using a conventional probe with two parallel fibers. In this study, Monte Carlo simulations and optical phantom experiments were conducted to investigate how angulation of the emitting fiber affects the probed volume to allow for the detection of acute breaches. Difference in intensity magnitude between cancellous and cortical spectra increased with the fiber angle, suggesting that outward angulated fibers are beneficial in acute breach scenarios. Proximity to the cortical bone could be detected best with fibers angulated at θ f = 45 ∘ for impending breaches between θ p = 0 ∘ and θ p = 45 ∘ . An orthopedic surgical device comprising a third fiber perpendicular to the device axis could thus cover the full impending breach range from θ p = 0 ∘ to θ p = 90 ∘ .

Steering light in fiber-optic medical devices: a patent review.

INTRODUCTION: Steering light is relevant to many medical applications that require tissue illumination, sensing, or modification. To control the propagation direction of light beams, a great variety of innovative fiber-optic medical devices have been designed. AREAS COVERED: This review provides a comprehensive overview of the patent literature on light beam control in fiber-optic medical devices. The Web of Science Derwent Innovation Index database was scanned, and 81 patents on fiber-optic devices published in the last 20 years (2001-2021) were retrieved and categorized based on the working principle to steer light (refraction/reflection, scattering, diffraction) and the design strategy that was employed (within fiber, at fiber end, outside fiber). EXPERT OPINION: Patents describing medical devices were found for all categories, except for generating diffraction at the fiber end surface. The insight in the different designs reveals that there are still several opportunities to design innovative devices that can collect light at an angle off-axis, reduce the angular distribution of light, or split light into multiple beams.

Advances in Imaging of Subbasal Corneal Nerves With Micro-Optical Coherence Tomography.

Purpose: To investigate the most peripheral corneal nerve plexus using high-resolution micro-optical coherence tomography (µOCT) imaging and to assess µOCT's clinical potential as a screening tool for corneal and systemic diseases. Methods: An experimental high-resolution (1.5 × 1.5 × 1 µm) µOCT setup was applied for three-dimensional imaging of the subbasal nerve plexus in nonhuman primates (NHPs) and swine within 3 hours postmortem. Morphologic features of subbasal nerves in µOCT were compared to ß3 tubulin-stained fluorescence confocal microscopy (FCM). Parameters such as nerve density, nerve distribution, and imaging repeatability were evaluated, using semiautomatic image analysis in form of a custom corneal surface segmentation algorithm and NeuronJ. Results: Swine and NHP corneas showed the species-specific nerve morphology in both imaging modalities. Most fibers showed a linear course, forming a highly parallel pattern, converging in a vortex with overall nerve densities varying between 9.51 and 24.24 mm/mm2. The repeatability of nerve density quantification of the µOCT scans as approximately 88% in multiple image recordings of the same cornea. Conclusions: Compared to the current gold standard of FCM, µOCT's larger field of view of currently 1 × 1 mm increases the conclusiveness of density measurements, which, coupled with µOCT's feature of not requiring direct contact, shows promise for future clinical application. The nerve density quantification may be relevant for screening for systemic disease (e.g., peripheral neuropathy). Translational Relevance: Technological advances in OCT technology may enable a quick assessment of corneal nerve density, which could be valuable evaluating ophthalmic and systemic peripheral innervation.

Proton density fat fraction of the spinal column: an MRI cadaver study.

BACKGROUND: The increased popularity of minimally invasive spinal surgery calls for a revision of guidance techniques to prevent injuries of nearby neural and vascular structures. Lipid content has previously been proposed as a distinguishing criterion for different bone tissues to provide guidance along the interface of cancellous and cortical bone. This study aims to investigate how fat is distributed throughout the spinal column to confirm or refute the suitability of lipid content for guidance purposes. RESULTS: Proton density fat fraction (PDFF) was assessed over all vertebral levels for six human cadavers between 53 and 92 years of age, based on fat and water MR images. According to their distance to the vertebra contour, the data points were grouped in five regions of interest (ROIs): cortical bone (-1 mm to 0 mm), pre-cortical zone (PCZ) 1-3 (0-1 mm; 1-2 mm; 2-3 mm), and cancellous bone ([Formula: see text] 3 mm). For PCZ1 vs. PCZ2, a significant difference in mean PDFF of between -7.59 pp and -4.39 pp on average was found. For cortical bone vs. PCZ1, a significant difference in mean PDFF of between -27.09 pp and -18.96 pp on average was found. CONCLUSION: A relationship between distance from the cortical bone boundary and lipid content could be established, paving the way for guidance techniques based on fat fraction detection for spinal surgery.

Micro-optical coherence tomography for high-resolution morphologic imaging of cellular and nerval corneal micro-structures.

We demonstrate the highest resolution (1.5×1.5×1 µm) micrometer optical coherence tomography (µOCT) imaging of the morphologic micro-structure of excised swine and non-human primate corneas. Besides epithelial, stromal, and endothelial cell morphology, this report focuses on investigating the most peripheral corneal nerve fibers, the nerve fibers of the subbasal plexus (SBP). Alterations of SBP nerve density and composition are reportedly linked to major neurologic disorders, such as diabetic neuropathy, potentially indicating earliest onsets of denervation. Here, the fine, hyperreflective, epithelial nerve structures located just above Bowman's membrane, are i) visualized using our µOCT prototype, ii) validated by comparison to fluorescence confocal microscopy (including selective immunohistochemical staining), and iii) segmented using state-of-the-art image processing. Here, we also introduce polarization sensitive (PS) µOCT imaging, demonstrating, to the best of our knowledge, the highest resolution corneal PS-OCT scans reported to date.

Corneal Stromal Filler Injection as a Novel Approach to Correct Presbyopia-An Ex Vivo Pilot Study.

Purpose: To evaluate the ex vivo feasibility of corneal stromal filler injection to create bifocality to correct presbyopia by flattening the central posterior corneal surface and thus increase refractive power. Methods: Femtosecond laser-assisted corneal stromal pockets of varying diameters close to the posterior corneal curvature were cut into rabbit eyes ex vivo. Subsequently, hyaluronic acid was injected to flatten the central posterior curvature. Refractive parameters were determined using perioperatively acquired three-dimensional optical coherence tomography (OCT) scans. Using micrometer-resolution OCT, corneal endothelial cell morphology and density were evaluated. Results: Following filler injection into the corneal stromal pockets, a fair volume-dependent increase of central refractive power up to 4 diopters (dpt) was observed. Unremarkable refractive changes of the peripheral posterior (3 mm, 0.20 ± 0.11 dpt; 2 mm, 0.11 ± 0.10 dpt) and the anterior corneal curvature (3 mm, 0.20 ± 0.34 dpt; 2 mm, 0.33 ± 0.31 dpt) occurred. Only negligible changes in astigmatism were observed. Different sizes of optical zones could be established. Furthermore, no alterations of corneal endothelial morphology or endothelial cell density (2831 ± 356 cells/mm2 vs. 2734 ± 292 cells/mm2; P = 0.552) due to the adjacent laser treatment were observed. Conclusions: The ex vivo investigations proved the principle of injecting a filler material into femtosecond laser-created corneal stromal pockets close to the posterior corneal curvature as an efficacious, individually adjustable, and novel approach to correct presbyopia without ablating corneal tissue. Translational Relevance: Due to the aging population worldwide, presbyopia is an increasing problem; thus, our study may encourage further exploration to extend the treatment spectrum of clinically used femtosecond laser systems to correct presbyopia.

Prevalence of Mental Disorders in Martinique, French West Indies: A Community-based Epidemiological Study / Prevalencia de los trastornos mentales en Martinica, Antillas Francesas: un estudio epidemiológico comunitario

ABSTRACT Objective: This study aimed to estimate the prevalence of mental disorders in the population of Martinique, as part of the survey entitled 'Mental Health in the General Population - Images and Realities ' (Santé Mentale en Population Générale - Images et Réalités). The survey was a multicentre epidemiological study in the general population, conducted in mainland France and French overseas islands between 1997 and 2006, under the authority of the World Health Organization Collaborating Centre for Training and Research in Mental Health (Lille, France). Methods: The study took place in 2000. Participants aged 18 years or over were recruited in public places, using the quota sampling method, and interviewed using the Mini International Neuropsychiatric Interview. Results: A total of 900 participants (52.7% women) with a mean age of 43 years completed the survey. Lifetime prevalence of any mental disorder was 29%. Mood (15%) and anxiety disorders (17%) were the most frequent. The rate of suicide attempts was low (4.2% lifetime), while the frequency of suicidal thoughts was high (11% past month) and similar to the frequency in mainland France. Conclusion: Mental disorders, especially mood and anxiety disorders, were as frequent in Martinique as in mainland France. The lower rates of suicide attempts, in spite of high rates of suicidal thoughts, might deserve further investigation. Our results should strengthen the development of a system of diagnosis and care for these disorders, especially to prevent suicidal behaviours and reduce morbidity and mortality.

RESUMEN Objetivo: Este estudio tuvo por objeto estimar la prevalencia de los trastornos mentales en la población de Martinica, como parte de la encuesta intitulada 'Salud Mental en la Población General - Imágenes y Realidades ' (Santé mentale at Population Générale - Images et Réalités). La encuesta fue un estudio epidemiológico multicéntrico en la población general, realizado en Francia continental y en las islas francesas de ultramar entre 1997 y 2006, bajo la autoridad del Centro de Colaboración de la Organización Mundial de la Salud para la Formación y la Investigación de la Salud Mental (Lille, Francia). Métodos: El estudio tuvo lugar en el año 2000. Los participantes mayores de 18 años fueron reclutados en lugares públicos, utilizando el método de muestreo por cuotas, y entrevistados usando la Mini Entrevista Neuropsiquiátrica Internacional. Resultados: Un total de 900 participantes (52.7% mujeres) con edad promedio de 43 años completó la encuesta. La prevalencia de por vida de cualquier trastorno mental fue de 29%. Los estados de ánimo (15%) y los trastornos de ansiedad (17%) fueron los más frecuentes. La tasa de intentos de suicidio fue baja (4.2% por tiempo de vida), mientras que la frecuencia de los pensamientos suicidas fue alta (11% el mes pasado) y similar a la frecuencia en la Francia continental. Conclusión: Los trastornos mentales, especialmente los estados de ánimo y los trastornos de ansiedad, eran tan frecuentes en Martinica como en la Francia continental. Las tasas más bajas de intentos de suicidio, a pesar de los altos índices de pensamientos suicidas, podrían merecer investigación adicional. Nuestros resultados deben fortalecer el desarrollo de un sistema de diagnóstico y cuidado para estos trastornos, especialmente para prevenir comportamientos suicidas y reducir la morbilidad y la mortalidad.

Knowledge, attitudes and practices of pregnant women in Martinique in the immediate aftermath of the Zika virus outbreak.

INTRODUCTION: The WHO and the HCSP recognize the Zika virus as a public health problem of international concern primarily because of the foetal risks. During the epidemic in Martinique, several modifications to the normal obstetrical follow-up were set up and information had to be delivered to pregnant women about these modifications, the attitudes to prevent infection and the signs motivating additional visits. The objective of our work was to evaluate the knowledge, attitudes and practices of pregnant women in Martinique about the risks associated with Zika infection during pregnancy in the immediate aftermath of the epidemic. MATERIALS AND METHODS: A descriptive cross-sectional survey was conducted from February to May 2017. It took place through an anonymous and standardized face-to-face questionnaire. The questions dealt with the pregnant women general knowledge about the virus, information disseminated by media on this subject, the potential risks, the protective measures taken and the monitoring throughout the pregnancy in case of infection. RESULTS: The total sample consisted of 297 pregnant women. Despite a weak adherence to individual and domestic protection recommendations, we found a good level of knowledge about Zika virus from pregnant women in Martinique. The fetal risk in case of maternal infection was known for 96.6% of those surveyed, individual protective measures were followed by 64.6% of women, 77.0% knew where to go in case of suspected infection, and 79.4% reported that the modifications in follow-up mainly concerned ultrasound monitoring. CONCLUSION: The awareness campaign on zika virus had a significant impact on population's knowledge and main practical information was correctly captured. The information did not spill excessive fear. Nevertheless, modification of individual behavior appeared harder to obtain.

Simple and complex rule induction performance in young and older adults: contribution of episodic memory and working memory.

This study tested the hypothesis that part of the age-related decline in performance on executive function tasks is due to a decline in episodic memory. For this, we developed a rule induction task in which we manipulated the involvement of episodic memory and executive control processes; age effects and neuropsychological predictors of task performance were investigated. Twenty-six younger (mean age, 24.0; range, 19-35 years) and 27 community-dwelling older adults (mean age, 67.5; range, 50-91 years) participated. The neuropsychological predictors consisted of the performance on tests of episodic memory, working memory, switching, inhibition and flexibility. Performance of the older adults was worse for the learning and memorization of simple rules, as well as for the more demanding executive control condition requiring the manipulation of informational content. Episodic memory was the only predictor of performance on the simple learning and memorization task condition whereas an increase in rule induction complexity additionally engaged working memory processes. Together, these findings indicate that part of the age-related decline on rule induction tests may be the result of a decline in episodic memory. Further studies are needed that examine the role of episodic memory in other executive function tasks in aging.

Vitamin D deficiency, vitamin D receptor gene polymorphisms and cardiovascular risk factors in Caribbean patients with type 2 diabetes.

AIM: The prevalence of diabetes in the French West Indies is three times higher than in mainland France. We aimed to assess the associations between vitamin D deficiency, vitamin D receptor (VDR) gene polymorphisms and cardiovascular risk factors in Caribbean patients with type 2 diabetes (T2D). METHODS: In this cross-sectional study of 277 patients, 25-hydroxyvitamin D was measured by radioimmunoassay. FokI, BsmI, ApaI and TaqI single nucleotide polymorphisms (SNPs) of the VDR gene were genotyped. Analysis of covariance and logistic regression were performed. RESULTS: The study included 76 patients of Indian descent and 201 patients of African descent. The prevalence of vitamin D deficiency (<20 ng/mL) was 42.6%. When patients were classified into groups with (G1) and without (G2) vitamin D deficiency, there were no significant differences in age, systolic blood pressure, low-density lipoprotein cholesterol and HbA(1c), although body mass index was significantly higher in G1. Vitamin D deficiency was significantly associated with increased diastolic blood pressure and triglyceride levels, and reduced high-density lipoprotein cholesterol (P<0.05). Prevalence of vitamin D deficiency was decreased in patients carrying the f allele of FokI (OR: 0.52; P=0.02) and the aa genotype of ApaI (OR: 0.46; P=0.05). BsmI and TaqI SNPs were not associated with vitamin D deficiency. CONCLUSION: The rate of vitamin D deficiency was high in our T2D patients, and was associated with the VDR gene FokI and ApaI polymorphisms and cardiovascular risk profile. Measurements of vitamin D may help to detect T2D patients with cardiovascular risk, and VDR polymorphisms might explain why vitamin D deficiency is so frequently seen in some T2D patients.

[Arterial-hypertension prevalence in the general population of Martinique]. / Prévalence de l'hypertension artérielle en population générale à la Martinique.

BACKGROUND: Since 1996, arterial hypertension has been recognized as one of the main health priorities in Martinique. However, its prevalence in the general population has never been measured. Furthermore, obesity is increasing in many countries and studies have shown that hypertension is more frequent in obese people than in people with normal body mass index. The objective of this survey is to measure hypertension prevalence in the general population and to study the link between hypertension, weight status and socioeconomic level. METHODS: Cross-sectional study of randomly selected homes in randomly selected geographical islets. All household members in these homes constituted the eligible population. Arterial hypertension was defined as systolic pressure greater than 140mmHg and/or diastolic pressure greater than 90mmHg and/or antihypertensive treatment. Weight status was estimated using the body mass index. RESULTS: Study concerned 1504 persons aged 16 years or older with a sex-ratio of 0.7 and an average age of 48.3 years for men and 48.5 years for women, p=0.88. The prevalence rate of hypertension is 29% [IC(95%): 25.9-31.8] in the sample and declines to 22.5% [IC(95%): 20.1-25.1] using weighted data. The prevalence rate is 33.1% [IC(95%): 30.2-36.6] for overweight and 20.1% [IC(95%): 17.8-22.6] for obesity. Being overweight is more frequent among persons with hypertension than among ones with normal blood pressure, 73.0 versus 47.4%; p<0.001. In those with hypertension, overweight does not differ significantly between men and women, but the prevalence of obesity is greater among women than among men (35.7 versus 20.6 %, p<0.05). CONCLUSION: The high prevalence of both hypertension and obesity in the general Martinican population has been confirmed by this study. Prevention actions are required to decrease the cardiovascular risk in this population.

Visual phenotype of multiple sclerosis in the Afro-Caribbean population and the influence of migration to metropolitan France.

PURPOSE: To describe the visual phenotype of multiple sclerosis (MS) in the Afro-Caribbean population living in Martinique (French West Indies) and to specify the influence of the migration to metropolitan France on ocular impairment. DESIGN: Prospective consecutive observational case series. METHODS: A complete ophthalmologic examination was performed. PARTICIPANTS: A total of 112 patients of Afro-Caribbean origin with MS satisfying McDonald's diagnostic criteria, divided into 53 cases (47.3%), the non-migrant patients (group NM), who had never left the Caribbean basin, and 59 cases (52.7%), the migrant patients (group M), who had lived in metropolitan France for at least 1 year before age 15. RESULTS: MS first manifested as an impairment of the optic nerve in 41 cases (36.6%): 25 cases (47.1%) in group NM and 16 cases (27.1%) in group M. Visual function was recovered in 13/25 cases (52%) in group NM compared to 13/16 cases (81%) in group M. Two-thirds of patients presented with a clinical ocular impairment, which was bilateral in 58.5% of cases in group NM. Fourteen cases (12.5%) met the criteria of neuromyelitis optica, nine cases (17%) in group NM and five cases (8.5%) in group M. In group NM, when the initial visual attack did not regress, the visual Expanded Disability Status Scale (EDSS) score was 5+/-1.5 ; 75% of patients had monocular blindness and 50% binocular. CONCLUSIONS: In the non-migrants (group NM), MS manifested more frequently with an optical neuropathy, the ocular impairment was more severe, and corresponded to neuromyelitis optica in 17% of the cases; a visual presentation and the absence of complete recovery from the first attack represented a factor of poor prognosis. This series is the largest description of the visual phenotype of MS in patients of African origin. The results confirm the preferential impairment of the optic nerve in the black population in the course of the disease. The migration towards an area of high prevalence of MS influences the visual phenotype in terms of a lower incidence and less severe prognosis of ocular impairment.

Calcium-sensing receptor-mediated ERK1/2 activation requires Galphai2 coupling and dynamin-independent receptor internalization.

The calcium-sensing receptor (CaR) recently has been shown to activate MAP kinase (ERK1/2) in various cell types as well as in heterologous expression systems. In this study we show that the CaR agonist NPS R-467 (1 microm), which does not activate the CaR by itself, robustly activates ERK1/2 in the presence of a low concentration of Ca(2+) (0.5 mm CaCl(2)) in human embryonic kidney (HEK) cells permanently expressing the human CaR (HEK-hCaR). Ca(2+) (4 mm) also activates ERK1/2 but with differing kinetics. CaR-dependent ERK1/2 activation begins to desensitize to 4 mm Ca(2+) after 10 min, whereas there is no desensitization to NPS R-467/CaCl(2) as late as 4 h. Moreover, recovery from desensitization occurs as rapidly as 30 min with 4 mm CaCl(2). Pretreatment of HEK-hCaR cells with concanavalin A (250 microg/ml) to block CaR internalization completely eliminated the NPS R-467/CaCl(2)-mediated ERK1/2 activation but did not block the 2-min time point of 4 mm Ca(2+)-mediated ERK1/2 activation. Neither dominant-negative dynamin (K44A) nor dominant-negative beta-arrestin inhibited ERK1/2 activation by either CaR agonist treatment, suggesting that CaR-elicited ERK1/2 signaling occurs via a dynamin-independent pathway. Pertussis toxin pretreatment partially attenuated the 4 mm Ca(2+)-ERK1/2 activation; this attenuated activity was completely restored by co-expression of the Galpha(i2) (C351I) but not Galpha(i1) (C351I) or Galpha(i3) (C351I) G proteins, PTX-insensitive G protein mutants. Taken together, these data suggest that both 4 mm Ca(2+) and NPS R-467/CaCl(2) activate ERK1/2 via distinguishable pathways in HEK-hCaR cells and may represent a nexus to differentially regulate differentiation versus proliferation via CaR activation.

Functional evidence for a role of vascular chymase in the production of angiotensin II in isolated human arteries.

BACKGROUND: In human arteries, angiotensin-converting enzyme (ACE) inhibitors incompletely block the production of angiotensin (Ang) II from Ang I. This ACE-independent production of Ang II appears to be caused by serine proteases, one of which presumably is chymase. However, several serine proteases may produce Ang II, and the exact role of chymase in the vascular production of Ang II has never been directly evaluated using selective chymase inhibitors. METHODS AND RESULTS: Rings of human mammary arteries were subjected to either Ang I or the chymase-selective substrate [pro,(11) D-Ala(12)] Ang I in the absence or the presence of the ACE inhibitor captopril, the serine protease inhibitor chymostatin, or the selective chymase inhibitor C41. Captopril only partially inhibited (by 33%) the response to Ang I. In the absence of captopril, C41 markedly reduced (by 44%) the response to Ang I, and this effect was identical to that of chymostatin. C41 also significantly reduced the response to Ang I in the presence of captopril, although this inhibitory effect was slightly less than that of captopril in combination with chymostatin. [Pro,(11)D-Ala(12)] Ang I induced potent contractions that were not affected by captopril but were abolished by chymostatin and markedly reduced by C41. In addition, we found that prior treatment of the patients with an ACE inhibitor did not affect the in vitro response to Ang I (in the absence or the presence of captopril) or to [Pro,(11)D-Ala(12)] Ang I. CONCLUSIONS: Our results reinforce the hypothesis that chymase is a major serine protease implicated in the ACE-independent production of Ang II in human arteries.

A description of human T-lymphotropic virus type I-related chronic interstitial keratitis in 20 patients.

OBJECTIVE: This study aimed to describe a syndrome that the authors call human T-lymphotropic virus type I-related chronic interstitial keratitis. METHODS: A consecutive series of 194 human T-lymphotropic virus type I-infected patients (divided into 119 patients with human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis and 75 asymptomatic human T-lymphotropic virus type I carriers) was systematically examined. RESULTS: Twenty patients (10.3%) had bilateral anterior stromal lesions made up of approximately 10 elevated, rounded or cloudy whitish opacities that were more or less confluent. The opacities were characteristically situated at the periphery of the anterior stroma, and the visual axis remained unaffected. The interstitial keratitis was chronic and unresponsive to topical administration of corticosteroids. It was mainly observed in patients affected by human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis among whom there were 18 cases (15.1%), as opposed to two cases (2.7%) in asymptomatic carriers. CONCLUSION: A new cause of interstitial keratitis is reported. Human T-lymphotropic virus type I infection may have a much broader spectrum of ocular manifestations than previously described. As with the other manifestations of human T-lymphotropic virus type I infection, corneal lesions could be linked to a lymphoplasmocytic infiltration of the stroma leading to corneal opacities.

An active ribonucleotide reductase from Arabidopsis thaliana cloning, expression and characterization of the large subunit.

In all living organisms, deoxyribonucleotides, the DNA precursors, are produced by reduction of the corresponding ribonucleotides catalyzed by ribonucleotide reductase. In mammals as in Escherichia coli, the enzyme consists of two proteins. Protein R1 is the proper reductase as it contains, in the substrate binding site, the reducing active cysteine pair. Protein R2 provides a catalytically essential organic radical. Here we report the cloning, expression, purification and characterization of protein R1 from Arabidopsis thaliana. Expression in E. coli was made possible by coexpression of tRNAArg4 which is required for the utilization of AGA and AGG as codons for arginines. Protein R1 shows extensive similarities with protein R1 from mammals: (a) it shows 69% amino-acid sequence identity to human and mouse R1 protein; (b) it is active during CDP reduction by dithiothreitol, in the presence of protein R2 [Sauge-Merle, S., Laulhère, J.-P., Coves, J., Ménage, S., Le Pape, L. & Fontecave, M. (1997) J. Biol. Inorg. Chem. 2, 586-594]; (c) activity is stimulated by thioredoxin and ATP and is inhibited by dATP, showing that as in the mammalian enzyme, the plant ribonucleotide reductase seems to be allosterically regulated by positive (ATP) and negative (dATP) effectors.

In Azotobacter vinelandii, the E1 subunit of the pyruvate dehydrogenase complex binds fpr promoter region DNA and ferredoxin I.

In Azotobacter vinelandii, deletion of the fdxA gene that encodes a well characterized seven-iron ferredoxin (FdI) is known to lead to overexpression of the FdI redox partner, NADPH:ferredoxin reductase (FPR). Previous studies have established that this is an oxidative stress response in which the fpr gene is transcriptionally activated to the same extent in response to either addition of the superoxide propagator paraquat to the cells or to fdxA deletion. In both cases, the activation occurs through a specific DNA sequence located upstream of the fpr gene. Here, we report the identification of the A. vinelandii protein that binds specifically to the paraquat activatable fpr promoter region as the E1 subunit of the pyruvate dehydrogenase complex (PDHE1), a central enzyme in aerobic respiration. Sequence analysis shows that PDHE1, which was not previously suspected to be a DNA-binding protein, has a helix-turn-helix motif. The data presented here further show that FdI binds specifically to the DNA-bound PDHE1.

Is there any relationship between interleukin-6/interleukin-6 receptor modulation and endogenous interleukin-6 release in metastatic malignant melanoma patients treated by biochemotherapy?

During recent years it has become clear that the production of most cytokines could play an important role in malignancies. We previously demonstrated that a high endogenous interleukin-6 (IL-6) level is significantly correlated with a high tumour burden and resistance to biochemotherapy in metastatic malignant melanoma patients. However, little is known about the origin of IL-6 and the pattern of IL-6 receptor (IL-6R) expression. In this report, we studied the expression of IL-6R and intracellular IL-6 using flow cytometry in tumour cells provided by fine-needle aspiration of lymph nodes and palpable metastatic lesions from 14 patients refractory to biochemotherapy and six responder patients. Moreover, we established the relationship between these parameters and the serum IL-6 level. Our results demonstrated that, following treatment, the percentage of HMB45-positive (HMB45+) cells expressing functional IL-6R, intracellular IL-6 or both IL-6R and IL-6 significantly decreased in patients refractory to biochemotherapy. In contrast, in responder patients the percentage of HMB45+ cells expressing IL-6R increased and those expressing IL-6 remained stable. Regarding the serum IL-6 level, an 11-fold increase was observed in the patients refractory to biochemotherapy, but only a 1.8-fold increase in the responder patients. In conclusion, in metastatic malignant melanoma patients with a poor prognosis, the endogenous production of IL-6 is concomitant with a decrease in functional IL-6R and intracellular IL-6 expression, suggesting the involvement of an IL-6/IL-6R complex.