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Biomedical subjects

G Wilson

Publications and source records attributed to G Wilson.

At least 163 records · Page 9Linked to original sources

Vibrational Raman optical activity of glycoproteins.

This paper reports the first vibrational Raman optical activity (ROA) spectrum of a glycoprotein. The sample, orosomucoid (alpha 1-acid glycoprotein), shows ROA bands characteristic of a high beta-sheet content together with new bands which could be specific for the carbohydrate and its association with the protein. Our results suggest that ROA spectra of intact glycoproteins may contain information about both protein and carbohydrate conformation and the mutual influence on each other's stability and conformation.

Carbohydrate Conformation↗

Cell kinetics of renal cell carcinoma studied with in vivo iododeoxyuridine incorporation and flow cytometry.

In 29 patients with renal cell carcinoma tumor cell kinetics were studied by in vivo labeling with 100 mg. iododeoxyuridine given 3 to 7 hours before nephrectomy. Two to 6 samples were analyzed from each tumor after fixation in ethanol. Iododeoxyuridine was analyzed by specific antibodies using flow cytometric analysis of labeled cells and parameters, such as labeling index and potential tumor doubling time, could be determined. Samples from 28 tumors were evaluable. Mean labeling index of the tumors was 2.7%, which was significantly different from the 0.35% index in kidney cortex tissue. There was no statistical difference in labeling index among the clinical stages. The mean potential tumor doubling time in the tumor cells was 20.3 days, which was significantly different compared with 137.7 days in kidney cortex tissue. There was a frequent intra-tumoral heterogeneity of potential tumor doubling times. Diploid and aneuploid samples had significantly different potential tumor doubling (mean 37.4 and 12.5 days, respectively). Potential tumor doubling had a significant impact on the survival time (p = 0.004), which also was noted in the patients with aneuploid tumors (p = 0.003). Our study shows that in vivo incorporation of iododeoxyuridine successfully can be analyzed in renal cell carcinoma. Potential tumor doubling time gives valuable prognostic information on the clinical behavior of the patients.

Adult↗

MASA syndrome is due to mutations in the neural cell adhesion gene L1CAM.

MASA syndrome is a recessive X-linked disorder characterized by mental retardation, adducted thumbs, shuffling gait, aphasia and, in some cases, hydrocephalus. Since it has been shown that X-linked hydrocephalus can be caused by mutations in L1CAM, a neuronal cell adhesion molecule, we performed an L1CAM mutation analysis in eight unrelated patients with MASA syndrome. Three different L1CAM mutations were identified: a deletion removing part of the open reading frame and two point mutations resulting in amino acid substitutions. L1CAM, therefore, harbours mutations leading to either MASA syndrome or HSAS, and might be frequently implicated in X-linked mental retardation with or without hydrocephalus.

Aphasia↗

Karyotypic and ras gene mutational analysis in idiopathic myelofibrosis.

Karyotypic analysis was performed in a total of 69 patients with well-characterized idiopathic myelofibrosis. Karyotypic abnormalities were detected in 46% of cases examined during the chronic phase (29/63); with three abnormalities, del(13q), del(20q) and partial trisomy 1q, accounting for 75% of all abnormalities at diagnosis. The absence of del(5q), trisomy 8 and 21, as well as the rarity of monosomy 7, contrasts with pooled published data and may reflect our exclusion of closely related disorders, in particular MDS with fibrosis. Chromosomal aberrations increased to approximately 90% (8/9) in patients analysed during acute transformation. Mutational activation of codons 12, 13 and 61 of N-, Ha- and Ki-ras genes were assessed by polymerase chain reaction and hybridization with synthetic non-radioactive digoxigenin-labelled probes. Three mutations were detected in samples of peripheral blood DNA taken from 50 patients during the chronic phase of their disease: one N12 Asp (GGT-->GAT) and two N12 Ser (GGT-->AGT) mutations. The results from this study indicate that karyotypic abnormalities are present in at least 29% of cases at diagnosis and that del(13q), del(20q) and partial trisomy 1q are the most frequent findings. Ras mutations were relatively infrequent (6%) and appeared restricted to the N-ras gene. Karyotypic analysis at diagnosis was found to be of prognostic significance.

Adult↗

The effect of ultraviolet-B irradiation on the cell shedding rate of the corneal epithelium.

In this study cell shedding rates of the corneal epithelium were determined in vitro following a single suprathreshold dose of ultraviolet-B irradiation. Rabbit corneas were excised and superfused in pairs. The epithelial and endothelial surfaces were bathed with solutions containing essential ions and adjusted to appropriate pH and osmolality. One cornea in each pair was irradiated, while the other cornea served as a control. Shed cells were periodically collected from the corneal surface and the shedding rate determined by counting the number of cells in a 50 min time period. Following a latent period of about 3 h, the epithelial shedding rate accelerated, and remained elevated for at least 8 h after irradiation. This result suggests that suprathreshold doses of ultraviolet-B irradiation disrupt the normal orderly cell shedding process and homeostatic equilibrium of the corneal epithelium. The elevated cell shedding rate exposes subsurface nerve endings and causes the characteristic pain of photokeratitis.

Acridine Orange↗

Rapid tumor cell proliferation after induction chemotherapy in oropharyngeal cancer.

Tumor cell kinetics were studied in vivo in a series of 97 patients with oropharyngeal cancer. The duration of S phase (tS), the labeling index (LI), and the potential doubling time (Tpot) were obtained by flow cytometry measurements of a tumor biopsy obtained after intravenous injection of 200 mg 5-bromodeoxyuridine to the patient. The mean LI was 9.7% (standard deviation [SD], 5.4), the mean tS was 10.1 hours (SD, 3.6), and the mean Tpot was 4.6 days (SD, 3.5). No significant relationship was found between the Tpot or LI and the size of the tumor, nodal status, histological grade, or the site of the primary within the oropharynx. Conversely, aneuploid tumors had longer tS (P < .001), higher LI (P < .001), and shorter Tpot (P < .05) than the diploid tumors. The mean LI and Tpot of the tumors obtained after induction chemotherapy were significantly higher and shorter, respectively, than those measured before any treatment. The data strongly suggest that rapid tumor cell proliferation frequently occurs in oropharyngeal cancer which had responded poorly to chemotherapy.

Aged↗

Play behavior and communication between deaf and hard of hearing children and their hearing peers in an integrated preschool.

Sixty preschoolers (30 deaf and hard of hearing, 30 hearing) were observed in their integrated school during "centers" and outdoor play. Half the children experienced auditory communication and half total communication modes of communication. All children had known their classmates for six months to three years. It was found that all children preferred to play and communicate with same-hearing status children, however 63% of all children communicated with children of other-hearing status. Amounts of social play and communication differed somewhat between the two communication environments, and context of interaction was related to the behavior and communication of children who were deaf and hard of hearing. Implications are discussed for the education of young children who are deaf and hard of hearing--specifically that educational and social benefits accrue to those who are integrated throughout the school day (across context) and have access to hearing classmates and classmates who are deaf and hard of hearing.

Child, Preschool↗

The effect of hypoxia on the shedding rate of the corneal epithelium.

The reason a cell leaves the corneal epithelial surface at a particular time is not understood. It is likely that a cell must depend on metabolic energy to accomplish this task successfully and with minimal disruption to the epithelial surface and barrier. The hypothesis under test is that the epithelium is directly dependent on atmospheric oxygen to maintain a normal cell shedding rate. Rabbit corneas were excised in pairs and the surfaces bathed with appropriate media for 400 minutes at 304 mOsm/kg and pH 7.4. The epithelial surface of one cornea was bathed with a normoxic solution as a control, while the other cornea was anoxic. Solutions were collected from the epithelial surface at 50 minute intervals. Cell counts of shed corneal epithelial cells were made by staining with acridine orange and viewing with fluorescence microscopy. Stromal thickness was measured at the beginning and at 400 minutes to confirm hypoxia. The results show that hypoxia does reduce the rate at which cells are shed, at least for collections made during the first 50 minutes (P < 0.01). However, by 150 minutes there was no difference between the hypoxic cornea and the control. This result suggests that cell shedding is dependent on oxygen only during the early part of a period of hypoxia. When the hypoxia is prolonged, other mechanisms intervene which preserve the normal shedding rate.

Acridine Orange↗

Balloon electric shock ablation. A surgical technique for treatment of ventricular tachycardia: influence of endocardial scar on depth of ablation achieved.

Balloon electric shock ablation is a surgical technique that has been used for treatment of ventricular tachycardia. However, little is known about the energy requirements and precise electrode array best suited to achieve effective ablation of the target area while limiting injury to the surrounding myocardium. This study was designed to determine the effects of endocardial scar (often present at the "site of origin" of clinical ventricular tachycardia) on depth of ablation resulting from balloon electric shock ablation. A chronic canine model of endocardial scar (3.9 +/- 0.6 mm thick) was developed with the use of balloon electric shock ablation techniques. We compared depth of ablation achieved with balloon electric shock ablation with low-energy shocks (22 J per bead) in normal dogs versus those with chronic endocardial scar. No difference was found in depth of ablation in normal dogs and in the scar model (7.2 +/- 1.2 mm versus 6.2 +/- 1.0 mm). Depth of injury expressed as a percentage of wall thickness was not different in the two groups (61% +/- 11% versus 57% +/- 3%). We conclude that the presence of endocardial scar does not influence depth of injury resulting from balloon electric shock ablation. This data provides guidance for clinical application of the technique as a "closed heart" surgical approach for control of ventricular tachycardia. The data are also discussed in relation to energy levels currently used for direct current catheter ablation in patients with ventricular tachycardia.

Animals↗

Protection from radiation-induced damage to spermatogenesis by hormone treatment.

Infertility caused by killing of the spermatogonial stem cells occurs frequently in men treated for cancer with radiotherapy and chemotherapy. We investigated whether pretreatment of rats with testosterone plus estradiol, which reversibly inhibits the completion of spermatogenesis and protects spermatogonial stem cells from procarbazine-induced damage, would also protect these cells from radiation. Adult male LBNF1 rats were implanted for 6 weeks with capsules containing testosterone and estradiol and then irradiated with doses from 2.5-7.0 Gy. Controls were irradiated with 1.8-3.5 Gy. Implants were removed 1 day after irradiation, and all animals were killed 10 weeks later for assessment of stem cell survival by counting repopulating tubules in histological sections and by sperm head counts. At doses of 2.5 and 3.5 Gy the repopulation indices and sperm head counts were significantly higher (P < 0.001) in the rats treated with testosterone and estradiol than in the controls. Protection factors (dose-modifying factors) calculated from the dose-response curves were in the range of 1.5-2.2. Elucidation of the mechanism of protection is essential to apply it to clinical situations. The fact that the spermatogonia are protected against radiation as well as procarbazine indicates that the mechanism does not involve drug delivery or metabolism.

Animals↗

Performance-based and physiological measures of situational awareness.

Several situational awareness (SA) and workload measurement techniques were investigated in simulated air-to-ground missions. These techniques included measures of effectiveness, subjective ratings, performance measures, and physiological measures. The results demonstrated strengths and weaknesses in all of these techniques. Measures of effectiveness and subjective ratings suggested that the experimental manipulations were effective in altering SA. The performance measures produced mixed results. Physiological measures detected some intriguing effects in the EEG. Overall, the complexity of the relationship between SA and workload encourages the use of multiple tools in any SA evaluation.

Adult↗

The spectrum of "complicated spastic paraplegia, MASA syndrome and X-linked hydrocephalus". Contribution of DNA linkage analysis in genetic counseling of individual families.

X-linked hydrocephalus and the X-linked MASA syndrome (Mental retardation. Adducted thumbs, Shuffling gait and Aphasia) both have a variable clinical spectrum with great overlap. Data from DNA linkage analysis placed the locus for both conditions at Xq28. On clinical and molecular grounds it has been hypothesized that both MASA syndrome and X-linked hydrocephalus are caused by a mutation in the same gene at Xq28. There is no significant clinical marker in the obligate female carriers and prenatal diagnosis by ultrasound is not reliable; DNA analysis can offer an improved genetic counseling for the families and more reliable prenatal diagnosis. In the gene encoding for Ll, a neural cell adhesion molecule and located at Xq28, several different mutations have been reported in X-linked hydrocephalus families and in a MASA family. We report data on DNA linkage analysis in 6 families with X-linked hydrocephalus/MASA syndrome. These data illustrate the importance of DNA linkage analysis in the individual family; they also show, however, the problem of studying small families. Genetic heterogeneity cannot be excluded.

Abortion, Eugenic↗

Recombinant Leishmania surface glycoprotein GP63 is secreted in the baculovirus expression system as a latent metalloproteinase.

A gene encoding the Leishmania surface metalloproteinase, GP63, was modified using the polymerase chain reaction to obtain effective secretion of recombinant GP63 (reGP63) in the baculovirus insect cell expression system. The coding region for the N-terminal signal peptide (SP) of GP63 was modified to resemble the SP for the GP67 envelope protein from the budded virus form of Autographa californica nuclear polyhedrosis virus. To prevent processing at the C-terminus with a glycosyl phosphatidylinositol anchor and the subsequent membrane anchoring of reGP63 in insect cells, the coding region for a putative SP at the C-terminus of GP63 was deleted. The reGP63 protein was glycosylated and secreted as a latent metalloproteinase in the baculovirus expression system. The reGP63 protein was purified from serum-free medium using concanavalin A lectin affinity chromatography, with a yield of 1 mg/l. The purified Leishmania reGP63 was secreted as a latent proteinase. Treatment of reGP63 with HgCl2 resulted in activation of full proteinase activity and a concomitant decrease in M(r). The mechanism of the activation of Leishmania reGP63 is consistent with that of other members of the family of matrix-degrading metalloproteinases.

Amino Acid Sequence↗

In vivo measurement of the potential doubling time by flowcytometry in oropharyngeal cancer treated by conventional radiotherapy.

PURPOSE: Experimental and clinical studies suggest that the pre-treatment potential doubling time could be predictive of tumor control in patients treated by conventional radiotherapy and could help to identify the rapidly growing tumors for which accelerated radiotherapy is required. METHODS AND MATERIALS: To test this hypothesis, we studied prospectively 48 patients with a squamous cell carcinoma of the oropharynx and treated by conventional radiotherapy (70 Gy/7 weeks). The duration of S phase, the labeling index and the potential doubling time were obtained by flowcytometry measurements of a tumor biopsy obtained after injection of 200 mg bromodeoxyuridine to the patient. RESULTS: Three parameters were significantly associated with an increased risk of relapse namely the tumors size (T4; p < 0.01), the nodal status (> or = N2; p < 0.05) and the site of the primary within the oropharynx (p = 0.08). The S phase, labeling index, DNA index and potential doubling time were not significantly associated with an increased risk of relapse. However when considering only the T2 subgroup of patients, high labeling indexes and short potential doubling time were associated with an increased risk of relapse: the mean pre-treatment potential doubling time of the tumors which relapsed was 3.21 versus 5.5 days when there was no evidence of local relapse (p < 0.05). The mean labeling index for the group of tumors associated with a tumor recurrence was 11.7% compared to 7.3% when there was no evidence of relapse (p = 0.02). CONCLUSION: Factors other than proliferation play a role in determining the outcome of oropharyngeal cancers treated by conventional radiotherapy. However there was a significant correlation between short potential doubling time, high labeling index and tumor recurrence in the T2 subgroup of patients. The finding of significance for potential doubling time and labeling index in the T2 subset of tumors may be a reflexion of the more homogeneous nature of these tumors with regard to prognostic variables.

Aged↗

Effect of flushing of the liver graft upon plasma calcium and magnesium concentrations.

Previous studies of total and ionized calcium in the plasma of liver transplant recipients have been conducted in patients with preexisting liver disease or who received blood transfusion. The intraoperative decline in plasma total and ionized calcium has been attributed to the effects of liver disease and/or the citrate in transfused blood. The present study was conducted in normal porcine recipients of liver stored either with EuroCollins or University of Wisconsin (UW) solution for 6 hr, compared with livers flushed with Ringer's lactate without storage. No blood transfusion was given. Mean total plasma calcium levels declined significantly after storage with UW solution to a nadir approximately 65-70% of preoperative levels. This decline persisted for two to five days. Mean levels of plasma ionized calcium declined lowest after flushing with UW solution but only to 82% of preoperative (NS). There was an increase in plasma total magnesium in the recipients of livers flushed with EuroCollins or UW solutions, which resolved within 30 min and which was probably related to magnesium content of the flushing solution. It is concluded that while the changes in plasma total and ionized calcium are moderate and of little clinical significance, they could be aggravated under clinical conditions by massive blood transfusion. Changes in plasma magnesium seemed to be directly attributable to the magnesium content of flushing solutions but the same relationship did not exist for changes in plasma calcium.

Animals↗

In vitro nasal transport across ovine mucosa: effects of ammonium glycyrrhizinate on electrical properties and permeability of growth hormone releasing peptide, mannitol, and lucifer yellow.

Transport of growth hormone releasing peptide across ovine nasal mucosa in the absence or presence of ammonium glycyrrhizinate (AMGZ) was studied in vitro. Ovine nasal mucosa was stripped from underlying cartilage and mounted in Ussing chambers. Transepithelial conductance (Gt) and short-circuit current (Isc) were monitored during experiments to assess tissue viability and integrity. Radiolabeled mannitol (Man; MW 182) and growth hormone releasing peptide (GHRP, SK&F 110679; MW 873) were employed to measure transport rates across the epithelium, and fluorescence spectroscopy was employed to measure rates of lucifer yellow (LY; MW 521) transport. Effects of AMGZ on ovine nasal mucosal viability and transport were determined from changes in electrical properties of fluxes of [3H]GHRP, [3H]Man, and LY. Results demonstrate that electrical properties of ovine nasal mucosa are stable over the time course of the experiments (Gt = 8.3 +/- 0.5 mS/cm2 and Isc = 3.7 +/- 0.2 microEq/hr.cm2; n = 21). Man fluxes were comparable in the mucosal (m)-to-serosal (s) and s-to-m directions [0.10 +/- 0.01 (n = 17) and 0.10 +/- 0.01 (n = 4) %/hr.cm2, respectively]. Transport of GHRP and LY in the m-s direction was similar to that of Man [0.08 +/- 0.01 (n = 11) and 0.09 +/- 0.01 (n = 3) %/hr.cm2, respectively]. GHRP flux was equivalent in the m-s and s-m directions. GHRP did not significantly alter ion transport processes as indicated by the lack of any change in Gt or Isc.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗