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Biomedical subjects

D Martin

Publications and source records attributed to D Martin.

At least 109 records · Page 6Linked to original sources
PubMed2001

Transcriptional regulation of the mosquito vitellogenin gene via a blood meal-triggered cascade.

In anautogenous mosquitoes, a blood meal is required for activation of genes encoding yolk protein precursors (YPP). Vitellogenin (Vg), the major YPP gene, is transcribed at a very high level following blood meal activation. It is expressed exclusively in the female fat body, the tissue producing most of mosquito hemolymph and immune proteins. In this paper, we analyzed the upstream region of the Aedes aegypti Vg gene in order to identify regulatory elements responsible for its unique expression pattern. To achieve this goal, we analyzed the gene using transgenic Drosophila and Aedes as well as DNA-binding assays. These analyses revealed three regulatory regions in the 2.1 kb upstream portion of the Vg gene. The proximal region containing binding sites to EcR/USP, GATA, C/EBP and HNF3/fkh is required for the correct tissue- and stage-specific expression at a low level. The median region carrying sites for early ecdysone response factors E74 and E75 is responsible for hormonal enhancement of Vg expression. Finally, the distal GATA-rich region is necessary for extremely high expression levels characteristic of the Vg gene. The present work elucidates the molecular basis of blood meal-dependent expression of this mosquito gene, laying the foundation for mosquito-specific expression cassettes with predictable stage and tissue specificity.

5' Flanking Region↗
PubMed2001

Intrathecal HIV-1 envelope glycoprotein gp120 induces enhanced pain states mediated by spinal cord proinflammatory cytokines.

Perispinal (intrathecal) injection of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein gp120 creates exaggerated pain states. Decreases in response thresholds to both heat stimuli (thermal hyperalgesia) and light tactile stimuli (mechanical allodynia) are rapidly induced after gp120 administration. gp120 is the portion of HIV-1 that binds to and activates microglia and astrocytes. These glial cells have been proposed to be key mediators of gp120-induced hyperalgesia and allodynia because these pain changes are blocked by drugs thought to affect glial function preferentially. The aim of the present series of studies was to determine whether gp120-induced pain changes involve proinflammatory cytokines [interleukin-1beta (IL-1) and tumor necrosis factor-alpha (TNF-alpha)], substances released from activated glia. IL-1 and TNF antagonists each prevented gp120-induced pain changes. Intrathecal gp120 produced time-dependent, site-specific increases in TNF and IL-1 protein release into lumbosacral CSF; parallel cytokine increases in lumbar dorsal spinal cord were also observed. Intrathecal administration of fluorocitrate (a glial metabolic inhibitor), TNF antagonist, and IL-1 antagonist each blocked gp120-induced increases in spinal IL-1 protein. These results support the concept that activated glia in dorsal spinal cord can create exaggerated pain states via the release of proinflammatory cytokines.

Animals↗
PubMed2001

Cardiorespiratory and metabolic responses to injection of bicuculline into the hypothalamic paraventricular nucleus (PVN) of conscious rats.

Stimulation of the PVN increases mean arterial pressure (MAP) and heart rate (HR). However, little is known about its role in modulating ventilation. We tested the hypothesis that the stimulation of the PVN by microinjection of bicuculline methiodide (BMI), a gamma-aminobutyric acid (GABA)(A) receptor antagonist, increases ventilation in conscious rats. Oxygen consumption was also evaluated to determine if the ventilatory responses were associated with increases in metabolic rate. Male Sprague--Dawley rats were instrumented with femoral catheters to measure MAP and HR and cannulae were implanted 1 mm above the PVN. After 5 to 7 days of recovery, metabolic, ventilatory, and cardiovascular responses to artificial cerebrospinal fluid (aCSF) and BMI were evaluated. Rats were given a 50 nl unilateral microinjection of aCSF (the vehicle control) followed by 50 n1 of BMI (1 mM) into the other side. Microinjection of BMI significantly increased MAP compared to aCSF (145+/-4 vs. 124+/-5 mmHg, P<0.02), HR to 460+/-17 from 362+/-22 breaths/min (P<0.01). Ventilation increased by 300% (P=0.01) by stimulating frequency of breathing (176+/-14 compared to 79+/-12 breaths/min, P<0.005) and increasing tidal volume. Concomitantly, O(2) consumption doubled (P<0.006). These data suggest that in the PVN GABA receptors may be important regulators of cardiopulmonary and metabolic function in conscious rats.

Animals↗
PubMed2001

Population pharmacokinetic-pharmacodynamic modelling of S 15535, a 5-HT(1A) receptor agonist, using a behavioural model in rats.

The pharmacokinetic-pharmacodynamic relationship of S 15535 (1-(benzodioxan-5-yl) 4-(indan-2-yl)piperazine) and its active 5-hydroxy metabolite S 32784 (1-(benzodioxan-5-yl) 4-(5-hydroxyindan-2-yl)piperazine), and buspirone as a reference, were studied in male Wistar rats using a behavioural model of anxiety by determining the reduction in the number of fear-induced ultrasonic vocalisations. S 15535 and buspirone were administered p.o. and i.v. S 32784, present in man but not in rat, was administered i.v. The pharmacokinetics and pharmacokinetic-pharmacodynamic relationships were described using non-linear mixed effects modelling. The no-drug effect was constant and all compounds were active in the model, reducing ultrasonic vocalisations immediately after administration. The sigmoid E(max) model was used to describe the pharmacokinetic-pharmacodynamic relationships, with E(max) values of a 90% decrease in baseline ultrasonic vocalisations. Corrected for plasma protein binding, all compounds showed similar potency. The study shows that ultrasonic vocalisations can be considered a suitable endpoint for the anxiolytic effect when used in conjunction with non-linear mixed effects modelling to overcome the limited sampling and effect measurements.

Animals↗
PubMed2001

VH gene replacement in thymocytes.

The quasi-monoclonal (QM) mouse has a functionally rearranged H chain gene inserted into its natural position in the IgH locus. In this position, the H chain gene is subject to many of the same activities as normally arranged H chain genes, including somatic hypermutation, V(H) gene replacement, and class switch recombination. Here, we have used this mouse strain to determine some of the rules that govern the V(D)J recombination activity of the IgH locus in thymus. We focused on the requirements for V(H) gene replacement. In normal mice, thymic DJ(H) rearrangements are common, but VDJ(H) rearrangements are not. We found intermediate products of V(H) replacement in double-positive CD4(+)CD8(+) cells of the QM thymus, demonstrating that the inserted V(H) gene was accessible and ruling out the possibility that a V(H) gene per se cannot be rearranged in the thymus. We found transcripts from the knocked-in H chain gene of QM, but no mu H chain protein was detectable in thymocytes. Cloning and sequencing of these transcripts revealed that some had been generated by V(H) gene replacement. Corresponding signal joints could also be identified. These results suggest that neither a B cell-specific signal nor an Ig protein are necessary to activate V(H)-to-VDJ(H) joining in thymocytes. Possible mechanisms remaining to account for overcoming the barrier to V(H) joining in thymocytes include the insertion of a transcriptionally active gene segment and/or the inactivation of a silencer.

Animals↗
PubMed2001

Congenital syphilis surveillance and newborn evaluation in a low-incidence state.

OBJECTIVES: To evaluate congenital syphilis surveillance in Minnesota, to assess the evaluation and management of newborns at risk for congenital syphilis, and to assess prenatal syphilis screening. DESIGN: Case ascertainment and medical record review. SETTING: The 7-county Minneapolis-St Paul metropolitan area. PATIENTS: Newborns at risk for congenital syphilis during a 3-year period (1992-1994). MAIN OUTCOME MEASURES: The completeness of congenital syphilis case ascertainment, maternal demographic data, maternal syphilis management, newborn evaluation for and management of congenital syphilis, and hospital syphilis screening practices at delivery. RESULTS: Eighty mother-infant pairs who were at risk for congenital syphilis were identified from 3 sources. Using the Centers for Disease Control and Prevention's congenital syphilis case definition, 36 infants (45%) were classified as probable cases, 42 (53%) were classified as noncases, and 2 (3%) were syphilitic stillbirths. Forty-seven women (59%) had syphilis serologic tests performed in the third trimester; only 37 (46%) had syphilis screening at delivery. Conditions of the mothers of 8 probable cases (22%) were diagnosed at delivery. Most probable cases (86%) were evaluated; only 56% were evaluated adequately. Twenty-five probable cases (69%) were treated. Most hospitals did not have formal policies for syphilis screening at delivery. The Minnesota Department of Health's congenital syphilis registry lacked sensitivity (39%) as a case ascertainment method. CONCLUSIONS: Clinicians should adhere to standardized protocols in the evaluation and management of at-risk newborns. Vigilant screening prenatally and at delivery and adequate follow-up are critical to reduce congenital syphilis. Improved surveillance data and resources are needed for the identification and follow-up of newborns at risk for congenital syphilis.

Adolescent↗
PubMed2001

Teneurin-2 is expressed in tissues that regulate limb and somite pattern formation and is induced in vitro and in situ by FGF8.

Teneurin-2 is a member of a novel family of transmembrane proteins characterized to date in fish, birds, mammals, and Drosophila (e.g., the pair-rule gene product Ten-m). We have shown that teneurin-2 is expressed by neurons in the developing avian visual system in a pattern complementary to the expression of teneurin-1 and that recombinant teneurin-2 induces morphologic changes in neuronal cells in culture (Rubin et al., 1999). Here we have used cRNA probes to two newly identified splice variants and a teneurin-2-specific antibody to determine whether teneurin-2 is also expressed outside the nervous system. Both reverse transcriptase-polymerase chain reaction and in situ hybridization indicate that the three splice variants known so far are coexpressed at sites of pattern formation during development. Teneurin-2 mRNAs and protein are found in the developing limbs, somites, and craniofacial mesenchyme. In addition to expression of teneurin-2 by the apical ectodermal ridge, teneurin-2 transcripts also appear transiently at sites of tendon development. Teneurin-2 expression patterns were strikingly similar to those of fibroblast growth factor 8 (FGF8). In agreement with the overlapping expression pattern, FGF8-coated beads implanted into chicken limb buds induced the ectopic expression of teneurin-2 and soluble FGF8 induced teneurin-2 in limb explant cultures. Thus, teneurin-2 could act downstream of FGF8 during morphogenesis.

Alternative Splicing↗
PubMed2001

Effect of luminance level on electro-encephalogram alpha-wave synchronisation.

A control system for the remote activation of electronic devices, based on alpha-wave synchronisation, must be robust over a wide range of lighting conditions. This study investigates the effect that low light levels have on the increase in amplitude of the occipital alpha-wave component of the human electro-encephalogram spectrum in response to eye closure. Measurements of the time required for the amplitude of the occipital alpha wave to increase above a predetermined threshold, upon eye closure, were taken from 21 subjects and at four illuminances, ranging from 2 x 10(-1) lx to 2 x 10(-5) lx. The light source used to provide these illuminances was a featureless, uniformly illuminated white paper that subtended 30 degrees of the visual field. Statistical analysis showed that the time to exceed threshold (TTET) upon eye closure was not independent (p< 0.001) of illuminance, and that the main source of this lack of independence occurred at the lowest illuminance, 2 x 10(-5) lx. At this luminance, the median TTET value was 15.0s. However, at 2 x 10(-4) lx, the median value of the TTET was 4.2s. This is a sufficiently short time for device activation, and therefore a control system based on alpha-wave synchronisation is functional at very low light levels.

Adolescent↗
PubMed2001

Carriage of Neisseria meningitidis among household contacts of patients with meningococcal disease in New Zealand.

The aims of this study were to estimate carriage prevalence, identify factors predictive of carriage, and compare strains of Neisseria meningitidis isolated from patients with meningococcal disease and their household contacts. A total of 954 contacts of 160 patients had a nasopharyngeal swab and an interview relating to factors associated with carriage. The carriage prevalence was 20.4% for Neisseria meningitidis, 11.3% for serogroup B, and 2.6% for serogroup C. Age-standardised carriage was higher in Maori (36.8%) than in Pacific Island (21.5%) or European/other (11.1%) ethnic groups. Factors associated with carriage were smoking, with personal smokers (odds ratio [OR] 2.5) and passive smokers (OR 1.6) having a higher carriage risk than those in smoke-free houses; ethnicity, with Maoris having a higher carriage risk than those of non-Maori or non-Pacific Island ethnicity (OR 2.2); gender, with males at higher risk than females (OR 1.7); and age, with 0-4-year-olds less likely and 15-24-year-olds more likely to be carriers than those over 25 years. Strong patient-contact clustering by meningococcal strain (chi-square1 = 16.7, P=0.00004) suggested an important role for the household setting in transmission. The low carriage prevalence of serogroup B Neisseria meningitidis among household contacts may reflect its low transmissibility but high virulence. No direct relationship was found between prevalence of ethnic-specific carriage and the incidence of meningococcal disease.

Adolescent↗
PubMed2001

Juxtafacet cyst of the lumbar spine. Clinical, radiological and therapeutic aspects in 28 cases.

OBJECT: A consecutive series of 28 "operated" juxtafacet cysts is reported. We emphasize the clinical and radiological aspects leading to diagnosis. We also discuss the results of the surgical treatment. MATERIAL AND METHODS: Medical information and radiological studies involving 28 patients were analyzed. Each patient has been operated on by decompressive laminectomy and resection of the cyst. The diagnosis was always confirmed by a pathological examination. The cyst most frequently occurred at the L4-L5 level (n = 18), and seldom at the L5-S1 (n - 6) or L3-L4 (n - 4) levels. RESULTS: The differential diagnosis from other pathological causes responsible for a radicular compression could not be done by physical examination. Spine X-rays or myelogram were nonspecific. Computed Tomography or CT-myelography could help in the diagnosis but MR imaging was the most sensitive. In our series, the respective sensitivities of these techniques are 56, 42 and 77%. The preoperative diagnosis was correct in 18 patients (64%). The cyst was sometimes adherent to the underlying dura, then significantly increasing the risk of dural tear and spinal fluid leak, especially when located at L3-L4 level. Surgical ablation lead to a complete recovery or an important improvement in 26 patients. CONCLUSIONS: The diagnosis of the juxtafacet cyst of the lumbar spine is better achieved by MRI. Surgery is the gold standard treatment, safe and long-term effective. When a total cyst removal with an internal facetectomy are performed, recurrence is exceptional.

Adult↗
PubMed2001

Analysis of the postulated interaction between the angiotensin II sub-type 1 receptor gene A1166C polymorphism and the insertion/deletion polymorphism of the angiotensin converting enzyme gene on risk of myocardial infarction.

A synergistic interaction between the insertion/deletion (I/D) polymorphism within the angiotensin-converting enzyme (ACE) gene and an A/C transversion at nucleotide position 1166 within the angiotensin II sub-type 1 receptor (AT1R) gene on risk of myocardial infarction has been reported. The risk associated with the ACE DD genotype increased with the number of AT1R C alleles present. To investigate this further, ACE I/D and AT1R A1166C genotypes were determined in 541 cases recruited at the time of infarction and 507 population-based controls. There was no difference in either the genotype distribution or allele frequencies between cases and controls for either the ACE polymorphism (P=0.48 and 0.35 respectively) or the AT1R polymorphism (P=0.35 and 0.21 respectively). Odds ratios for risk of MI associated with the ACE DD and AT1R CC genotypes were 1.09 (95% CI, 0.82-1.45) and 1.06 (0.67-1.68) respectively. 3.1% of cases versus 3.6% of controls were homozygous for both the D and C alleles (P=0.71). There was no increase in risk associated with the DD genotype in the presence of either one or two AT1R C alleles in the whole cohorts (OR 0.99, 95% CI 0.65-1.51 and 0.76, 95% CI 0.30-1.88, respectively) nor in sub-groups defined by specific risk factors. In conclusion, no evidence was found to support any interaction between the ACE gene I/D polymorphism and the ATIR gene A1166C transversion in determining the risk of myocardial infarction in the population studied.

Aged↗
PubMed2001

Poly(D,L-lactide) foams modified by poly(ethylene oxide)-block-poly(D,L-lactide) copolymers and a-FGF: in vitro and in vivo evaluation for spinal cord regeneration.

The first goal of this study was to examine the influence that poly(ethylene oxide)-block-poly(D,L-lactide) (PELA) copolymer can have on the wettability, the in vitro controlled delivery capability, and the degradation of poly(D,L-lactide) (PDLLA) foams. These foams were prepared by freeze-drying and contain micropores (10 microm) in addition of macropores (100 microm) organized longitudinally. Weight loss, water absorption, changes in molecular weight, polymolecularity (Mw/Mn) and glass transition temperature (Tg) of PDLLA foams mixed with various amounts of PELA were followed with time. It was found that 10wt% of PELA increased the wettability and the degradation rate of the polymer foams. The release of sulforhodamine (SR) was compared for PDLLA and PDLLA-PELA foams in relation with the foam porosity. An initial burst release was observed only in the case of the 90:10 PDLLA/PELA foam. The ability of the foam of this composition to be integrated and to promote tissue repair and axonal regeneration in the transected rat spinal cord was investigated. After implantation of ca. 20 polymer rods assembled with fibrin-glue, the polymer construct was able to bridge the cord stumps by forming a permissive support for cellular migration, angiogenesis and axonal regrowth.

Animals↗
PubMed2001

[Microsurgery and esthetic considerations. Two cases of heel reconstruction].

With two case reports of heel reconstruction on female patients the authors report the advantages and drawbacks of the two main types of reconstruction: free or regional flaps. Regional flaps are technically easy and reliable but their aesthetic after-effects on the donor site may be disabling, specially on the leg of a female patient. Microsurgery is technically more difficult and presents more complications specially on the lower limb. However, in certain conditions, and with the appropriate choice of donor site, free flaps authorize good quality reconstructions with minimal aesthetic after-effects.

Accidents, Occupational↗
PubMed2001

[Terminal-lateral nerve anastomoses. Preliminary clinical report of two cases].

Nerve regeneration is based on three phenomenons of critical importance: neurotropism, nerve guidance and neurotrophis. These principles allow understanding the mechanisms of nerve suture and grafting, but also the newly described end-to-side nerve anastomoses. In this procedure, the distal stump of a severed nerve is anastomosed on the lateral side of an intact nerve, with or without removal of the perineurium. Authors report their beginning experience with this procedure (ten cases) and discuss the early results. End-to-side anastomosis seems to be a useful and reliable technique for clinical nerve repair. Even if nerve grafting remains the gold standard to bridge nerve defects, one has nothing to loose if a few minutes, anastomosing the severed nerve on the lateral side of an intact nerve, rather than doing nothing.

Adolescent↗
PubMed2001

Effects of radiation on frozen lactate dehydrogenase.

Results concerning the influence of 6-MeV electron beam irradiation, of 2.45-GHz, 565-W microwaves, and of the combined electron and microwave irradiation, at -21 degrees C and -196 degrees C, on lactate dehydrogenase activity are presented. The microwave-irradiated samples exhibited a non-linear behaviour (successive activation and inactivation of the enzyme molecules), suggesting the major influence of the non-thermal component of microwave radiation. The combined electron and microwave irradiation led to a decrease of activity similar to the one caused by electron beam irradiation, which seemed to prove that microwave influence was insignificant in the dose, power and time ranges used. The radiation target analysis of the enzymatic decrease due to electron irradiation indicated a very large aggregation of the enzyme molecules. Our data suggest that radiation target analysis is not suitable to measure the molecular mass of lactate dehydrogenase, when frozen enzyme suspensions are irradiated. The D2O-protected enzyme, when exposed to electron irradiation, showed an even larger aggregation according to radiation target analysis, while the microwave irradiation of the protected enzyme led to a similar, though lesser, non-linear behaviour of the frozen enzyme molecules.

Electrons↗
PubMed2001

Intrathecal interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor exhibits an anti-allodynic action in a rat model of neuropathic pain.

The expression of interleukin-1beta and tumor necrosis factor has previously been shown to be up-regulated in the spinal cord of several rat mononeuropathy models. This present study was undertaken to determine whether blocking the action of central interleukin-1beta and tumor necrosis factor attenuates mechanical allodynia in a gender-specific manner in a rodent L5 spinal nerve transection model of neuropathic pain, and whether this inhibition occurs via down-regulation of the central cytokine cascade or blockade of glial activation. Interleukin-1 receptor antagonist or soluble tumor necrosis factor receptor was administered intrathecally via lumbar puncture to male Holtzman rats in a preventative pain strategy, in which therapy was initiated 1h prior to surgery. Administration of soluble tumor necrosis factor receptor attenuated mechanical allodynia, while interleukin-1 receptor antagonist alone was unable to decrease allodynia. Interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor, administered to both male and female rats in a preventative pain strategy, significantly reduced mechanical allodynia in a dose-dependent manner (P<0.01). The magnitude of attenuation in allodynia was similar in both males and females. Immunohistochemistry on L5 spinal cord revealed similar astrocytic and microglial activation regardless of treatment. At days 3 and 7 post-transection, animals receiving daily interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor exhibited significantly less interleukin-6, but not interleukin-1beta, in the L5 spinal cord compared to vehicle-treated animals. In an existing pain paradigm, in which treatment was initiated on day 7 post-transection, interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor attenuated mechanical allodynia (P<0.05) in male rats. These findings further support a role for central interleukin-1beta and tumor necrosis factor in the development and maintenance of neuropathic pain through induction of a proinflammatory cytokine cascade.

Animals↗
PubMed2001

[Vascularized bone pedicle grafts of the hand and wrist: literature review and new donor sites].

Some situations in hand surgery require vascularized bone grafts. Good mechanical strength and decreased time for bone healing may explain their use. Although many donor sites have been described, the authors were interested by donor sites with a blood supply provided by an accessory vessel not disturbing the perfusion of the hand. Literature review of the different donor sites demonstrate (a) Three sites at the dorsal aspect of the distal epiphysis and one at the dorsal distal ulna. Only the radialmost site has been regularly used for surgical application. (b) At the palmar aspect of the radial epiphysis, the pronator quadratus vascularised bone graft may be elevated in an antero or retrograde way. (c) Among the carpal bones, the pisiform and part of the capitate has been used as pedickled bone graft. (d) Metacarpals may also be a donor site. Description of sites at the proximal and distal part of the second metacarpal has been used for surgical applications. The authors describe a new site at the first metacarpal at the radiodorsal or uino-dorsal aspect which may be used as a composite bone-skin graft. A clinical application is presented. Clinical use of these pedicles graft is discussed and apply mainly for scaphoid nonunion and some case of Kienbock's disease. Distal stump reconstruction is possible with the new flap.

Bone Transplantation↗