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Biomedical subjects

S Boyer

Publications and source records attributed to S Boyer.

At least 19 recordsLinked to original sources

Reduction of bladder outlet resistance by selective stimulation of the ventral sacral root using high frequency blockade: a chronic study in spinal cord transected dogs.

PURPOSE: The use of electrical neural stimulation as treatment for neurogenic bladder is complicated by simultaneous contraction of the striated sphincter. This result is due to the composition of the ventral sacral roots, which contain somatic fibers innervating the external urethral sphincter and preganglionic parasympathetic fibers innervating the detrusor, among others. The somatic fibers have a larger caliber than the parasympathetic fibers and, as large diameter fibers, need a lower stimulus amplitude for activation than smaller fibers. Activation of the smaller fibers is always accompanied by activation of the larger fibers. We studied the effect of chronic application of selective combined low and high frequency current stimulation of the ventral sacral root on bladder evacuation and urethral resistance in chronically spinalized (spinal cord transected above the spinal micturition center) male dogs for daily bladder evacuation. MATERIALS AND METHODS: A total of 14 male mongrel dogs weighing 20 to 25 kg. underwent transection of the spinal cord at the T10 vertebra. The S2 ventral sacral root was wrapped with a bipolar electrode connected to a subcutaneous microstimulator. Daily bladder evacuation by neural stimulation with determination of the voided and residual urine volumes was done for 8 months. The animals were stimulated only with low frequency current during the 1-month spinal shock phase. Selective parameters of combined low frequency stimulation and high frequency blockade currents were subsequently applied for 6 months. For the last study month the animals were again stimulated by low frequency current alone. Bladder and urethral pressure as well as electromyography of the external urethral sphincter and pelvic floor muscles were evaluated monthly. Histopathological testing of the chronically stimulated nerve and external sphincter was performed. RESULTS: Of the 14 dogs 12 completed the followup study. During the shock phase with the application of low frequency only stimulation the animals voided 26% of mean functional bladder capacity with the early return of detrusor activity. Mean detrusor pressure plus or minus standard error of mean was 76.4 +/- 21.6 cm. water, while mean urethral pressure was 83.6 +/- 16.8 cm. water. During the application of selective combined low and high frequency stimulation 7 animals (58%) evacuated the bladder completely with post-void residual urine less than 10% of mean individual functional bladder capacity and 5 (42%) had mean post-void residual urine less than 20% of mean individual bladder capacity. Mean detrusor pressure was 73.5 +/- 20 cm. water and mean urethral pressure was 44 +/- 7.3 cm. water. There was a 45.19% reduction in the mean electromyography activity of the external sphincter. Stimulation of the dogs for the last month by low frequency current resulted in the voiding of 33% of mean bladder capacity with an increase in mean urethral pressure and electromyography activity. CONCLUSIONS: These results of reducing external sphincter activity by the simultaneous application of high frequency current blockade of the somatic fibers and activation of the autonomic fibers of the bladder by low frequency stimulation are promising.

Animals↗

Two differing presentations of optic nerve head drusen.

BACKGROUND: Optic nerve head drusen was recognized histologically in 1858 by Heinrich Muller The majority of optic nerve head drusen cases have been benign in nature. However, optic nerve head drusen can be visually devastating. CASE REPORTS: Two patients were diagnosed with optic nerve head drusen. They were similar in age and each had a best-corrected visual acuity of 20/20 OU. Although the diagnosis was the same, the disease affected each person very differently. One is currently asymptomatic; the other is legally blind secondary to severely constricted visual fields. These cases demonstrate the diversity of visual effects produced by optic nerve head drusen. Appropriate ocular workup, including visual fields, B-scan ultrasonography, computed tomography, and other tests, are presented. CONCLUSION: There is no existing treatment for optic nerve head drusen. Proper diagnosis and patient education is the best-available modality of care. Patients need to be aware of potential complications which, while rare, can affect vision. Visual-field testing can aid in monitoring for subtle changes in vision.

Blindness↗

Expression of human papilloma virus E7 protein causes apoptosis and inhibits DNA synthesis in primary hepatocytes via increased expression of p21(Cip-1/WAF1/MDA6).

The impact of human papilloma virus (HPV16) E7 proteins and retinoblastoma (RB) antisense oligonucleotides upon mitogen-activated protein kinase (MAPK)-mediated inhibition of DNA synthesis via p21(Cip-1/WAF1/MDA6) (p21) was determined in primary hepatocytes. Prolonged activation of the MAPK pathway in p21(+/+) or p21(-/-) hepatocytes caused a large decrease and increase, respectively, in DNA synthesis. Either transfection with RB antisense oligonucleotides, expression of wild type E7, or RB binding mutant E7 (C24S) proteins increased p21 levels and reduced DNA synthesis in p21(+/+) hepatocytes. RB antisense oligonucleotides and E7 proteins increased apoptosis in p21(+/+), but not p21(-/-), hepatocytes. Expression of wild type E7 increased DNA synthesis above control levels in p21(-/-) cells, which was additive with prolonged MAPK activation. In contrast, expression of mutant E7 did not alter DNA synthesis above control levels in p21(-/-) cells and was supra-additive with prolonged MAPK activation. Antisense ablation of RB in p21(-/-) hepatocytes had a weak stimulatory effect upon DNA synthesis itself but enhanced the capacity of mutant E7 protein to stimulate DNA synthesis to the same level observed using wild type E7. The ability of prolonged MAPK activation to stimulate DNA synthesis in the presence of mutant E7 and antisense RB was additive. Collectively, the present data demonstrate that loss of RB function together with loss of p21 function plays an important role in the E7- and MAPK-dependent modulation of apoptosis and DNA synthesis in primary hepatocytes.

Animals↗

Implantable selective stimulator to improve bladder voiding: design and chronic experiments in dogs.

Among the treatments to enhance the bladder voiding, the sacral roots neurostimulation is one of the most promising techniques. The electrostimulation of sacral nerves provokes a simultaneous contraction of the detrusor muscle as well as the external urethral sphincter (EUS). A new simplified-architecture implantable stimulator with its wireless controller have been designed to investigate high-frequency inhibition stimulation strategies. This innovative technique based on high-frequency inhibition reduces sphincter activity during stimulation. Low-frequency current pulses also applied to the sacral roots induces contraction of the detrusor muscle resulting in low pressure voiding. Chronic experiments were carried out on ten male mongrel paraplegic dogs. One cuff electrode was implanted along with each stimulator for eight months. The animals were stimulated twice a day using the prototypes of our implantable selective stimulator while voided and residual urine volume were measured during the procedure. These experiments revealed that the proposed stimulation strategy enhances bladder voiding by more than 50% in comparison with low-frequency only stimulation. The residual urine volume was reduced to an average of 9% and low pressure micturition was achieved as shown by weekly cystourethrogram.

Animals↗

An update on HL7's XML-based document representation standards.

Many people know of HL7 as an organization that creates healthcare messaging standards. But HL7 is also developing standards for the representation of clinical documents (such as discharge summaries and consultation notes). These document standards comprise the HL7 Clinical Document Architecture (CDA). Last year we presented a high-level conceptual overview of the CDA. Since that time, CDA has entered HL7's formal ballot process (which when successful will make the CDA an ANSI-approved HL7 standard). This article delves into the technical details of the current CDA proposal. Note that due to space limitations, only a subset of CDA details can be described. Also, because the ballot process elicits considerable feedback, it is likely that the material presented here will undergo evolution prior to becoming a final standard. The most up-to-date information is available on HL7's web site (www.hl7.org).

Medical Records Systems, Computerized↗

Interaction of calicheamicin gamma1(I) and its related carbohydrates with DNA-protein complexes.

We report studies of the contribution of DNA structure, holding the sequence constant, to the affinity of calicheamicin gamma(1)(I) and its aryltetrasaccharide moiety for DNA. We used polynucleotide chains as models of known protein-binding sequences [the catabolite activator protein (CAP) consensus sequence, AP-1 and cAMP response element (CRE) sites] in their free and protein-bound forms. The proteins were selected to provide examples in which the minor-groove binding site for the carbohydrate is (CAP) or is not (GCN4) covered by the protein. Additionally, peptides related to the GCN4 and CREB families, which have different bending effects on their DNA-binding sites, were used. We observe that proteins of the CREB class, which induce a tendency to bend toward the minor groove at the center of the site, inhibit drug-cleavage sites located at the center of the free AP-1 or CRE DNA sites. In the case of GCN4, which does not induce DNA bending, there is no effect on calicheamicin cleavage of the CRE site, but we observe a GCN4-induced rearrangement of the cutting pattern in the AP-1 site. This effect may arise from either a subtle local conformational rearrangement not accompanied by bending or a localized reduction in DNA flexibility. Whereas GCN4 binding is not inhibited by the calicheamicin aryltetrasaccharide, binding of CAP to its DNA target is significantly inhibited, and calicheamicin cutting of DNA at the center of the CAP-DNA complex site is strongly reduced by protein binding. This result probably reflects steric inhibition of drug binding by the protein.

Aminoglycosides↗

HL7 document patient record architecture: an XML document architecture based on a shared information model.

The HL7 SGML/XML Special Interest Group is developing the HL7 Document Patient Record Architecture. This draft proposal strives to create a common data architecture for the interoperability of healthcare documents. Key components are that it is under the umbrella of HL7 standards, it is specified in Extensible Markup Language, the semantics are drawn from the HL7 Reference Information Model, and the document specifications form an architecture that, in aggregate, define the semantics and structural constraints necessary for the exchange of clinical documents. The proposal is a work in progress and has not yet been submitted to HL7's formal balloting process.

Humans↗

Early diabetes-induced changes in rat jejunal glucose transport and the response to insulin.

The effects of 1 day of streptozotocin-induced diabetes in rats on glucose transport across the brush border membrane (BBM) and basolateral membrane (BLM) prepared from jejunal enterocytes has been studied. The effects on glucose transport of treatment of diabetic animals with insulin to reduce to normal the elevated blood glucose levels has also been assessed. The maximum capacity (Vmax) for SGLT1-mediated glucose uptake by BBM vesicles was unaffected by diabetes or insulin treatment of diabetic rats. In contrast, Vmax for BLM glucose uptake was increased by 206% in diabetes, a response that could not be reversed by treatment with insulin. Western blotting of BBM for SGLT1 protein revealed a single band with a molecular weight of 73 kDa and the intensity of this band was unaffected by diabetes. However, an increased level of GLUT2 was noted in diabetic BLM and this was not a consequence of changes in glycaemic or insulin status. Diabetes hyperpolarised the BBM, implying an increased driving force for Na(+)-sugar co-transport but insulin treatment only partially reversed this enhanced potential difference. Benzamil (2 microns), an epithelial Na+ channel blocker, hyperpolarised the BBM of control but not diabetic enterocytes, implying that a reduced Na+ permeability was responsible for the diabetic hyperpolarisation. It was concluded that in early diabetes, before the onset of hyperphagia, a greater driving force for Na(+)-dependent BBM sugar transport together with increased GLUT2 activity at the BLM promotes sugar movement across the enterocyte. Possible triggers for the transport responses are discussed.

Animals↗

Streptozotocin diabetes and the expression of GLUT1 at the brush border and basolateral membranes of intestinal enterocytes.

Changes in membrane expression of sodium-dependent glucose transporter (SGLT1) and glucose transporter isoform (GLUT2) protein have been implicated in the increased intestinal glucose transport in streptozotocin-diabetes. The possible involvement of GLUT1 in the transport response, however, has not previously been studied. Using confocal microscopy on tissue sections and Western blotting of purified brush border membrane (BBM) and basolateral membrane (BLM), we have examined enterocyte expression of GLUT1 in untreated and in 1 and 21 day streptozotocin diabetic rats. In control enterocytes, GLUT1 was absent at the BBM and detected at low levels at the BLM. Diabetes resulted in a 4- to 5-fold increased expression of GLUT1 at the BLM and the protein could also be readily detected at the BBM. Insulin treatment of diabetic rats increased GLUT1 level at the BBM but was without effect on expression of the protein at the BLM.

Animals↗

Comparison of the 10-minute supine-30-minute tilt test with 24-hour ambulatory blood pressure for the diagnosis of diastolic systemic hypertension.

A variant of the protracted tilt test, the 10-minute supine -30-minute tilt test (10S-30TT), has been proposed by us for the evaluation of blood pressure (BP). The present investigation compares parameters of diastolic BP by 3 methods: office measurements, 10S-30TT, and 24-hour ambulatory monitoring; the last method served as a reference standard. Twenty patients presenting at the office with diastolic BP values ranging from 80 to 120 mm Hg (median 90) were studied. Statistically significant correlations were observed between the following parameters: diastolic office BP and average ambulatory awake diastolic BP (r = 0.64, p = 0.002); average tilt-test diastolic BP and average ambulatory awake diastolic BP (r = 0.69, p = 0.0006); frequency of elevated diastolic BP values during the tilt test and frequency of elevated ambulatory awake diastolic BP values (r = 0.69, p = 0.0007). Diastolic BP diagnosis scores exhibited strong correlation only between the ambulatory and tilt-test diagnosis (kappa = 0.70), but not between ambulatory and office BP diagnosis (kappa = 0.50). Based on the close correlation between results of the 10S-30TT and ambulatory monitoring in the evaluation of diastolic BP, we suggest that the faster and cheaper tilt test may serve as a substitute in certain categories of patients.

Adult↗

Direct measurement of the accumulation and mitochondrial conversion of nitric oxide within Chinese hamster ovary cells using an intracellular electron paramagnetic resonance technique.

We have developed an electron paramagnetic resonance (EPR) method for the nondestructive detection and quantification of intracellular NO in real time. Based upon this technique, we have obtained evidence for the metabolism of this bioregulatory molecule by mitochondria. Line-broadening of the EPR signal of a coal derivative, fusinite, was calibrated as a function of NO concentration in aqueous solution. The methodology was validated using two compounds which release NO in a controlled and predictable manner with first-order rate constants k1 = 5.0 x 0.10(-3) s-1 and k'1 = 3.4 x 10(-4) s-1 (35 degrees C). Fusinite was internalized in Chinese hamster ovary cells (CHO) by phagocytosis, after which the cells were allowed to consume the available O2, producing an hypoxic environment. The NO released from one of the NO donors, added to the culture fluid at an initial concentration of 50 microM, was directly measured in the intracellular environment as line-broadening of the fusinite EPR signal. The linewidth diminished with time, indicating that NO was being converted to a non-paramagnetic species by the cells with an apparent zero-order rate constant of 5 x 10(8) NO molecules cell-1 min-1 (20 degrees C). Addition of cyanide to the culture medium (5 mM final concentration) inhibited this disappearance of NO. NO also was converted in the presence of isolated mitochondria in the absence of oxygen. These observations suggest that under hypoxic conditions, there exists in CHO cells a metabolic pathway for the conversion of NO to diamagnetic species, which involves interactions with mitochondria.

Animals↗

Mechanisms of 3-carene-induced bronchoconstriction in the isolated guinea pig lung.

Inhaled 3-carene at a concentration of 5,000 mg/m3 caused bronchoconstriction in isolated, ventilated and perfused guinea pig lungs. This effect was inhibited by the cyclooxygenase inhibitor diclofenac (100 microM) and the thromboxane/prostaglandin endoperoxide-receptor antagonist L-670,596 (1 microM). 3-Carene exposure also increased the amount of thromboxane in the perfusate from the lungs. In cultured calf pulmonary arterial endothelial cells 3-carene caused a dose-related release of arachidonic acid. Thus, the results obtained in this experimental model may have implications in the understanding of the pathophysiology of 3-carene-induced obstructive pulmonary disease in humans.

Animals↗

Diagnosis of mucopolysaccharidoses in a clinically selected population by urinary glycosaminoglycan analysis: a study of 2,000 urine samples.

Two thousand urine samples (from patients presenting with clinical features suggestive of a mucopolysaccharidosis, MPS) were analysed by a procedure that included a quantitative measurement of glycosaminoglycan (GAG) hexuronic acids (harmine reagent), a qualitative GAG analysis (cellulose acetate electrophoresis) and a study of urinary oligosaccharide patterns. One hundred and seventy MPS and 29 oligosaccharidosis-affected patients were found, but 23 MPS patients among the 170 would have been missed by use of a quantitative procedure only. Fourteen of these (mainly MPS IV A) were detected on the basis of abnormal electrophoresis and the 9 others on the basis of abnormal urinary oligosaccharide patterns (MPS IV B patients). Our results emphasize that normal quantitative GAG excretion alone cannot rule out a diagnosis of MPS; qualitative analysis is also required, as well as oligosaccharide screening.

Adolescent↗

Relationship between Charcot-Marie-Tooth 1A and Smith-Magenis regions. snU3 may be a candidate gene for the Smith-Magenis syndrome.

The juxtacentromeric region of the human chromosome 17 short arm (17p11.2-p12) contains genes involved in the Charcot-Marie-Tooth type 1A disease (CMT1A) and the Smith-Magenis syndrome (SMS). CMT1A is associated with a duplication of a short segment whereas SMS is linked to microdeletions, extending toward the centromere. We describe the construction and analysis of a 5 Mb YAC contig spanning the CMT1A duplicated segment and the distal part of four SMS microdeletions. We concluded that the YAC contig contains about 1Mb of genomic DNA which is deleted in the four SMS patients analysed. Moreover two YACs contain both STS deleted in SMS (U3) and STS duplicated in CMT1A (5H5), but the proximal breakpoint associated with the CMT1A duplication is not the same as the distal SMS breakpoint we studied. Finally we located five new STS in SMS deletion. Two of them, a microsatellite (D17S805(23)) and the gene coding for small nuclear RNA U3, have been localized in the contig we described. We may also note that snU3 is the first expressed sequence localized in an SMS deletion so far. The possible participation of this gene in the SMS phenotype is discussed.

Base Sequence↗

Measurements of pertinent concentrations of oxygen in vivo.

A new method able to measure the concentration of oxygen in complex biological systems, including in vivo, has been developed using low-frequency EPR and newly characterized free radicals that are very sensitive to the concentration of oxygen. The free radicals (fusinite and lithium phthalocyanine) are very stable in tissues (for at least 150 days), apparently nontoxic, and can reflect oxygen concentrations that are less than the Km of cytochrome oxidase (0.1 microM or lower). Their biological stability is indicated by the fact that repeated measurements with fusinite of the concentration of oxygen in skeletal muscle have been made in the same animal for more than 150 days without any change in sensitivity or signs of toxicity.

Animals↗

Recent evolutionary origin of the expression of the glial fibrillary acidic protein (GFAP) in lens epithelial cells. A molecular and genetic analysis of various mouse species.

We have investigated the phylogenetic distribution of the glial fibrillary acidic protein (GFAP) in lens epithelial cells (LEC) of various mouse species within the genus Mus. We have shown that lens GFAP is expressed in mice of the Mus musculus complex and in Mus spicilegus and Mus macedonicus species (L.GFAP(+) phenotype) while it is absent in Mus spretus, Mus caroli and Mus cooki species (L.GFAP(-) phenotype). Our results argue in favour of one of the phenograms illustrating the probable phylogenetic relationships between these species in the genus Mus. In animals where lens GFAP was immunodetected, Northern blots of lens RNA extracts hybridized with a mouse GFAP cDNA probe, revealed a single 2.7 kb band. Comparative Northern blot analysis of lens tissue from L.GFAP(+) mice or of brain tissue from L.GFAP(+) or L.GFAP(-) mice did not show any size heterogeneity of the GFAP mRNA. The pattern of the GFAP immunostaining of astroglial cells in brain was identical in both L.GFAP phenotypes. Analysis of interspecific crosses showed that the L.GFAP(+) character is transmitted in a dominant fashion and seems to be linked to the Mus musculus Gfap gene. In this study we have also confirmed the localization of the mouse Gfap gene on chromosome 11.

Animals↗