Biomedical subjects

M A Skinner

Publications and source records attributed to M A Skinner.

At least 37 records · Page 2Linked to original sources

PubMed2001

Cancer of the thyroid gland in infants and children.

Carcinoma of the thyroid gland is unusual in children and represents only about 3% of pediatric malignancies. Surgical management is the principal method of treatment, but there is considerable controversy regarding exactly how much of the thyroid gland should be removed for adequate treatment. There also is controversy regarding the use of fine-needle aspiration (FNA) in the evaluation of potentially neoplastic thyroid lesions. In this report, the pertinent literature is reviewed regarding these issues. Moreover, this report will discuss recent discoveries that have elucidated some of the molecular biological events responsible for the development of thyroid cancer.

Child↗

PubMed2001

Vaccination of animals against Mycobacterium bovis.

Vaccination could potentially be used as a practical means of controlling bovine tuberculosis in countries in which a wildlife reservoir of the disease is present, and also in those countries which cannot afford conventional control strategies. An understanding of the processes involved in the protective immune response to tuberculosis is desirable for the rational development and testing of new vaccines for tuberculosis. The authors review current knowledge regarding the processes involved in protective immune responses to tuberculosis, much of which has been derived from studies in mice. This knowledge is discussed in relation to the problem of using vaccination to induce protective immunity in cattle, deer and wildlife. Challenge models have now been developed to test candidate vaccines in many domestic animals and wildlife species and these models are being used to evaluate tuberculosis vaccines. Most studies of the efficacy of tuberculosis vaccines in target animals have focused on the use of bacillus Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis. Recent advances in immunology and the molecular biology of mycobacteria have greatly increased the options for candidate vaccines and future studies will test new types of vaccines including new attenuated strains of M. bovis, sub-unit protein vaccines and recombinant deoxyribonucleic acid vaccines. Several of these vaccines have shown promising results when tested in small animal models. Although progress has been made in the development of vaccine delivery systems for animals, the technical problems associated with vaccination of wildlife remain a challenge.

Animals↗

PubMed2000

Immunological approaches to the control of tuberculosis in wildlife reservoirs.

Attempts to eradicate tuberculosis from cattle and farmed deer in some countries have been frustrated by the existence of wildlife reservoirs of Mycobacterium bovis infection. Possum control programmes in New Zealand using poisons have shown clearly that the brushtail possum is an important source of infection for cattle and farmed deer, and the sum of evidence strongly suggests that badgers serve as a source of infection for cattle in the UK. Bovine tuberculosis can only be eradicated from these countries by controlling M. bovis infection in both wildlife and domestic animals. The most promising options for control of M. bovis infection in wildlife in the longer term include the development of a tuberculosis vaccine for wildlife and a strategy for biological control of possums. The aim of this review is to address the problems and approaches involved in the control of wildlife tuberculosis from an immunological perspective.

Animals↗

PubMed2000

Improved technique for transient expression and negative strand virus rescue using fowlpox T7 recombinant virus in mammalian cells.

The suitability of recombinant T7 polymerase produced using either the highly attenuated MVA strain of vaccinia (MVA-T7) or fowlpox virus (FP-T7) for transient expression and negative strand virus rescue was compared in two mammalian cell lines (MDBK and Vero) and in primary cells of bovine, ovine and caprine origin. Such primary cells are more permissive for the growth of wild type strains of morbilliviruses, such as Rinderpest virus and Peste des petits ruminants virus. MVA-T7 was found to be highly cytopathic in the primary cells, multiplying rapidly and killing the cells within 3-5 days of infection, even when very low multiplicities of infection (MOI) were used. In contrast, FP-T7, which appeared to express similar amounts of T7 polymerase, was found to be non-cytopathic in a variety of primary and established cell lines of mammalian origin and was suitable for use in virus rescue experiments. MDBK cells and primary cells, unlike Vero cells, could not be efficiently transfected and so were unsuitable for virus rescue. Optimal conditions for rinderpest virus rescue in Vero cells were established using FP-T7 in place of MVA-T7. This system will be suitable for rescuing other viruses which grow in Vero cells.

Animals↗

PubMed2000

Dendritic cells infected with recombinant fowlpox virus vectors are potent and long-acting stimulators of transgene-specific class I restricted T lymphocyte activity.

The identification of dendritic cells (DC) as the major antigen-presenting cell type of the immune system, combined with the development of procedures for their ex vivo culture, has opened possibilities for tumour immunotherapy based on the transfer of recombinant tumour antigens to DC. It is anticipated that the most effective type of response would be the stimulation of specific, MHC class I restricted cytotoxic T lymphocytes capable of recognising and destroying tumour cells. In order to make this approach possible, methods must be developed for the transfer of recombinant antigen to the DC in such a way that they will initiate an MHC class I restricted response. Here, we demonstrate that murine DC infected with a recombinant fowlpox virus (rFWPV) vector stimulate a powerful, MHC class I restricted response against a recombinant antigen. A rFWPV containing the OVA gene was constructed and used to infect the DC line DC2.4. The infected DC2.4 cells were found to stimulate the T-T cell hybridoma line RF33. 70, which responds specifically to the MHC class I restricted OVA peptide SIINFEKL. The stimulatory ability of the rFWPV-infected DC2.4 cells lasted for at least 72 h after infection and was eventually limited by proliferation of uninfected cells. By comparison, DC2.4 cells pulsed with synthetic SIINFEKL peptide stimulated RF33.70 well initially, but the stimulatory ability had declined to zero by 24 h after pulsing. FWPV infection of DC2.4 up-regulated MHC and costimulatory molecule expression. rFWPV was also found to infect both immature and mature human DC derived from cord blood CD34+ progenitors and express transgenes for up to 20 days after infection. We conclude that rFWPV shows promise as a vector for antigen gene transfer to DC in tumour immunotherapy protocols.

Animals↗

PubMed2000

Routine insertion of a silastic spring-loaded silo for infants with gastroschisis.

BACKGROUND/PURPOSE: Gastroschisis traditionally is managed by emergency operating room closure (EC), with a silo reserved for cases that cannot be closed primarily. The authors recently began using routine insertion of a SILASTIC (Dow Corning, Midland, MI) spring-loaded silo (SLS), followed by elective closure. METHODS: A total of 43 consecutive neonates with gastroschisis were treated between 1993 and 1998. RESULTS: Thirty patients underwent EC, and 13 underwent closure after insertion of a SLS (10 at bedside, 3 in the operating room). Eight infants treated by EC required staged repair. There were no differences with respect to gestational age, birth weight, gender, Apgar score, maternal age, or mode of delivery. Median length of stay was 32 days for EC and 25 days for SLS (P = .05). The SLS group required fewer days on a ventilator (4 v 6 days, P = .03) and had lower intraoperative (28 v 21, P = .02) and early postoperative peak airway pressures. The time to tolerate full feedings was 21 days for SLS and 27 days for EC (P = .07). The SLS group had fewer complications and a lower median hospital charge ($71,498 v $85,147; P = .05). CONCLUSION: SLS followed by elective repair permits gentle, gradual reduction of the viscera. When compared with EC, SLS is associated with significantly lower airway pressures, earlier extubation, fewer complications, and decreased length of stay and hospital charges.

Coated Materials, Biocompatible↗

PubMed2000

16q loss of heterozygosity and microsatellite instability in Wilms' tumor.

BACKGROUND/PURPOSE: Wilms' tumor is the most common renal malignancy of childhood. Loss of heterozygosity (LOH) at 16q is seen in about 17% of cases and has been associated with a poor prognosis. To more precisely define the pattern of 16q deletion exhibited by Wilms' tumor, the authors performed a detailed LOH analysis of 96 specimens using polymorphic microsatellite repeat markers. The authors also evaluated the neoplasms for the presence of microsatellite instability (MSI). METHODS: A total of 96 DNA samples were studied using polymerase chain reaction-based LOH analyses amplifying polymorphic microsatellite repeat markers. Screening for MSI using 2 additional genetic markers also was carried out. RESULTS: The authors found 16q LOH in 14 of the specimens evaluated. Comprehensive analysis of these LOH-positive specimens showed a region of loss spanning 16p11.2-q22.1 and a separate distal region of LOH at 16q23.2-24.2. The distal region of deletion is very small, estimated to be approximately 2.4 megabases. In addition to the observed LOH, 2 specimens were found to consistently exhibit MSI, which has not been reported previously in Wilms' tumor. CONCLUSIONS: The smallest consensus region of deletion in our analysis of Wilms' tumor 16q LOH measures 2.4 megabases at 16q23.2-q24.2. Additionally, MSI was present in a subset of tumor specimens suggesting that defects in DNA mismatch repair may contribute to the pathogenesis of Wilms' tumor.

Child↗

PubMed2000

Morphogenesis and release of fowlpox virus.

Release of fowlpox virus (FWPV) as extracellular enveloped virus (EEV) appears to proceed both by the budding of intracellular mature virus (IMV) through the plasma membrane and by the fusion of intracellular enveloped virus (IEV) with the plasma membrane. Based on the frequency of budding events compared to wrapping events observed by electron microscopy, FWPV FP9 strain seems to exit chick embryo fibroblast cells predominantly by budding. In contrast to vaccinia virus (VV), the production of FWPV extracellular virus particles is not affected by N(1)-isonicotinoyl-N(2)-3-methyl-4-chlorobenzoylhydrazine (IMCBH). Comparison of the sequence of the VV F13L gene product with its FWPV orthologue showed a mutation, in the fowlpox protein, at the residue involved in IMCBH resistance in a mutant VV. Glucosamine, monensin or brefeldin A did not have any specific effect on FWPV extracellular virus production. Cytochalasin D, which inhibits the formation of actin filaments, reduces the production of extracellular virus particles by inhibiting the release of cell-associated enveloped virus (CEV) particles from the plasma membrane. Involvement of actin filaments in this mechanism is further supported by the co-localization of actin with viral particles close to the plasma membrane in the absence of cytochalasin D. Actin is also co-localized with virus factories.

Actins↗

PubMed2000

Vaccination of cattle with Mycobacterium bovis culture filtrate proteins and interleukin-2 for protection against bovine tuberculosis.

In this study vaccines prepared from culture filtrate proteins (CFP) of Mycobacterium bovis and interleukin-2 (IL-2) were tested in cattle for their capacity to stimulate immune responses and to protect against an intratracheal challenge with virulent M. bovis. Nine groups of cattle were vaccinated with combinations of different doses of CFP and bovine IL-2 mixed with a monophosphoryl lipid A (MPL) adjuvant. An additional group was vaccinated with M. bovis BCG. Immune responses in b1P-IL-2-vaccinated animals differed from those seen in BCG-vaccinated animals by inducing high antigen-specific antibody responses and low levels of gamma interferon and IL-2 released from purified protein derivative-stimulated whole-blood cultures. In a concurrent experiment, additional animals were added to the high-dose CFP-IL-2, MPL control, and BCG groups and these expanded groups of animals were challenged intratracheally with virulent M. bovis. Although the lung lesion scores were significantly lower for both the CFP-IL-2-and BCG-vaccinated groups compared to the MPL control group, the overall level of protection was greatest for the BCG-vaccinated animals. There were more animals with extrathoracic spread of disease in the CFP-IL-2 group than in the other groups. While vaccination of cattle with M. bovis CFP gave an encouraging reduction in tuberculous lesions and did not induce a delayed-type hypersensitivity response to PPD, future CFP vaccines must prevent any extrathoracic spread of disease.

Animals↗

PubMed1999

beta(1) integrin binds the 16-kDa subunit of vacuolar H(+)-ATPase at a site important for human papillomavirus E5 and platelet-derived growth factor signaling.

Integrins mediate adhesive interactions between cells and the extracellular matrix, and play a role in cell migration, proliferation, differentiation, cytoskeletal organization, and signal transduction. We have identified an interaction between the beta(1) integrin and the 16-kDa subunit of vacuolar H(+)-ATPase (16K). This interaction was first isolated in a yeast two-hybrid screen and confirmed by coimmunoprecipitation and in in vitro binding assays using bacterially expressed proteins. Immunofluorescent studies performed in L6 myoblasts expressing both native and epitope-tagged 16K demonstrate co-localization with beta(1) integrin in focal adhesions. Deletion of the fourth of four transmembrane helices in 16K results in loss of interaction with beta(1) integrin in vitro and in the two-hybrid system, and less prominent staining in focal adhesions. This helix is also required for ligand-independent activation of platelet-derived growth factor-beta receptor signaling by the human papillomavirus E5 oncoprotein. Overexpression of 16K or expression of 16K lacking this helix alters the morphology of myoblasts and fibroblasts, suggesting that the interaction of 16K with integrins could be important for cell growth control. We also discuss the possible role 16K might play in integrin movement.

Amino Acid Sequence↗

PubMed1999

Intestinal obstruction after lung transplantation in children with cystic fibrosis.

BACKGROUND/PURPOSE: Distal intestinal obstruction syndrome (DIOS) occurs in 15% of patients with cystic fibrosis (CF). The authors reviewed their experience to determine the incidence, risk factors, and natural history of adhesive intestinal obstruction and DIOS after lung transplantation. METHODS: Eighty-three bilateral transplants were performed in 70 CF patients between January 1990 and September 1998. All were on pancreatic enzymes preoperatively, and none had preoperative bowel preparation. Fifty-six patients (80%) had prior gastrostomy (n = 54) or jejunostomy (n = 2). Eighteen patients (25.7%) had a previous laparotomy for meconium ileus (n = 8), fundoplication (n = 4), liver transplant (n = 1), jejunal atresia (n = 1), Janeway gastrostomy takedown (n = 1), pyloromyotomy (n = 1), free air (n = 1), or appendectomy (n = 1). RESULTS: After lung transplantation, 7 patients (10%) required laparotomy for bowel obstruction (6 during the same hospitalization, and 1 during a subsequent hospitalization). The causes of obstruction were adhesions only (n = 1), DIOS only (n = 2), and a combination of DIOS and adhesions (n = 4). Adhesiolysis was performed in the 5 patients with adhesions, and a small bowel resection was also performed in 1 patient. DIOS was treated by milking secretions distally without an enterotomy (n = 3) with an enterotomy and primary closure (n = 1) or with an end ileostomy and mucus fistula (n = 2). Five had recurrent DIOS early postoperatively. One resolved with intestinal lavage, 2 were treated successfully with hypaque disimpaction, and 2 underwent reoperation; 1 required an ileostomy. The most important risk factor for posttransplant obstruction was a previous major abdominal operation. Obstruction occurred in 7 of 18 (39%) who had undergone a prior laparotomy versus 0 of 52 who had not (P < .001, chi2). CONCLUSIONS: (1) The incidence of intestinal obstruction is high after lung transplantation in children with CF. (2) Previous laparotomy is a significant risk factor. (3) Recurrent obstruction after surgery for this condition is common. (4) Preventive measures such as pretransplant bowel preparation and early postoperative bowel lavage may be beneficial in these patients.

Adolescent↗

PubMed1999

Transanal one-stage Soave procedure for infants with Hirschsprung's disease.

PURPOSE: Many centers perform a one-stage pull-through procedure for Hirschsprung's disease (HD) diagnosed in infancy. The authors have developed a one-stage pullthrough procedure using a transanal approach that eliminates the need for intraabdominal dissection. METHODS: Nine children aged 3 weeks to 18 months with biopsy-proven HD underwent a transanal pull-through procedure over a 13-month period. A rectal mucosectomy was performed starting 0.5 cm proximal to the dentate line, and extending proximally to the level of the intraperitoneal rectum. In the first eight children, intraperitoneal position was confirmed with a laparoscope placed through a 3- to 5-mm port in the base of the umbilicus. The muscular sleeve was divided circumferentially to allow full-thickness mobilization of the rectosigmoid junction. Manual transanal traction permitted direct visualization and division of mesenteric vessels with transanal mobilization above the transition zone. Ganglion cells were confirmed by frozen section, and the bowel was transected. The rectal muscular cuff was divided longitudinally, and the anastomosis was completed. The laparoscope confirmed orientation and adequate hemostasis. In a ninth patient, the identical procedure was performed, but with the laparoscope used only for confirmation at the end of the procedure. RESULTS: Operative time, including frozen sections, averaged 194 minutes (range, 169 to 250 minutes), and the average length of bowel resected was 12 cm (range, 7.5 to 22 cm). Four of the nine patients were discharged on postoperative day (POD) 1, four on POD 2, and one patient with Down's syndrome was discharged on POD 6. Median follow-up was 6 months (range, 3 to 14 months). One death occurred 2.5 months postoperatively secondary to sudden infant death syndrome. Complications included postoperative apnea spells (n = 1), mild enterocolitis (n = 2), constipation (n = 1), anastomotic stricture(n = 1), and muscularcuff narrowing (n = 1); each responded to nonoperative management. Stool output has ranged from four to eight per day. CONCLUSION: A one-stage pull-through for HD can be performed successfully using a transanal approach without intraperitoneal dissection. This procedure is associated with excellent clinical results and permits early postoperative feeding, early hospital discharge, and no visible scars.

Anal Canal↗

PubMed1999

Experience with procedural sedation in a pediatric burn center.

BACKGROUND: Burn care requires daily debridement, dressing changes, and assessment regarding the need for skin grafting. These procedures are painful and may require an operating room environment. METHODS: The authors reviewed their experience with 912 consecutive procedural sedations (PS) in 220 pediatric burn patients over a 2-year period to identify what influence PS had on patient care. Median patient age was 32 months, and body surface area burn was 7.2%+/-6%. Pharmacological techniques included oral and intravenous medications and N2O. The authors included all sedations given in the burn treatment area and excluded all treatments given in the intensive care unit or emergency unit. RESULTS: PS allowed for early aggressive wound debridement, virtually eliminated the need for operating room debridement (used in only 22 patients), and eliminated patient discomfort and fear often associated with subsequent debridements. Burn wound-related complications occurred in 54 patients and included wound infection (n = 18), graft loss (n = 9), and pneumonia (n = 4). The incidence of PS complications was 7% with the most common problems including decreased arterial saturation (n = 41), emesis (n = 11), and agitation (n = 8). No patient required intubation or transfer to an intensive care unit bed. The average length of stay (LOS) for all patients was 8.7+/-6.2 days, and 6.2+/-3.8 days in the 200 patients not admitted to the intensive care unit. This compares favorably with the 9.5-day LOS of patients treated in 1990. CONCLUSIONS: PS in burn patients allows for early aggressive debridement, decreases the use of the operating room for debridement, and a decrease in length of stay when compared with our previous burn patients. PS has a modest risk of complications, enhances the family's cooperation and satisfaction with health care provided, and should be an integral part of burn care in children.

Adolescent↗

PubMed1999

Stage-dependent redistribution of the V-ATPase during bovine implantation.

The 16-kD subunit of the vacuolar H(+)-ATPase (V-ATPase), or ductin, is essential for the activity of this proton pump and has roles in intercellular communication and control of cell growth and differentiation. The V-ATPase is important for acidification-dependent degradation of tissue matrices through which some cell types move, and for pH regulation across some epithelial cell layers. Placentation involves intricate signaling, cell proliferation, and controlled invasion. We examined the distribution of three subunits of the V-ATPase in bovine trophoblast and endometrium at the time of implantation to determine the relationship of ductin expression to that of two other subunits, A (approximately 73 kD) and B (approximately 58 kD). Epithelial expression of all three subunits was observed, and in nonpregnant animals this expression was apical. As pregnancy proceeded, expression of all subunits became pericellular in luminal but not glandular epithelium, suggesting a redistribution of V-ATPase activity. The trophoblast expressed all three subunits during initial contact with the epithelium. In the stroma, ductin expression was reduced after implantation, and we discuss the possibility that ductin plays a role in the shifting communication between stromal and epithelial cells induced by embryo attachment. (J Histochem Cytochem 47:1247-1254, 1999)

Animals↗

PubMed1998

Women of reproductive age with endometriosis are not osteopenic.

OBJECTIVE: To determine whether women of reproductive age with endometriosis are osteopenic and whether bone density decreases with higher stages of endometriosis. DESIGN: A multicenter cross-sectional study was performed. SETTING: Thirty-nine gynecological clinics in the United States, Canada, and Puerto Rico. PATIENT(S): Two hundred forty-one women of reproductive age with laparoscopically proved endometriosis. INTERVENTION(S): Diagnostic laparoscopy, bone densitometry. MAIN OUTCOME MEASURE(S): Endometriosis stages according to the criteria of the American Society for Reproductive Medicine, lumbar spine bone mineral density (L2-L4) as measured by dual-energy x-ray absorptiometry. RESULT(S): The mean lumbar spine bone mineral density, as well as the distribution of bone mineral density, of the women with endometriosis was similar to that of a normal population. There were no significant differences between endometriosis stage groups I-IV regarding bone mineral density as well as body weight, body mass index, and height. CONCLUSION(S): Women of reproductive age with endometriosis are not osteopenic. More advanced stages of endometriosis are not associated with a decrease in lumbar spine bone mineral density.

Adolescent↗

PubMed1998

Goserelin acetate (Zoladex) with or without hormone replacement therapy for the treatment of endometriosis.

OBJECTIVE: To determine whether hormone replacement therapy (HRT) plus goserelin (Zoladex) is as effective as goserelin alone for the relief of pelvic symptoms of endometriosis and to determine whether it reduces both the loss of bone mineral density (BMD) and the physiologic side effects associated with goserelin therapy. DESIGN: Prospective, placebo-controlled study, open label for goserelin therapy and double-blind for HRT. SETTING: Forty-two teaching or community hospitals. PATIENT(S): Premenopausal women with symptomatic endometriosis. RESULT(S): Statistically significant mean decreases from baseline in the total pelvic symptom score and total subjective score were observed by week 24 for all three groups. There were no statistically significant treatment differences for change in total symptom score. Some degree of BMD loss occurred in the three groups; however, the percentage loss was consistently greater in the HRT0 group than in the HRT1 or HRT2 groups. When analyzed separately, no overall age effect on BMD change was seen in women >30 years of age versus women < or = 30 years. The HRT1 and HRT2 groups had fewer occurrences of hot flushes and vaginal dryness than did the HRT0 group. CONCLUSION(S): Goserelin plus HRT is as effective as goserelin alone in relieving pelvic symptoms of endometriosis and attenuates both the loss of BMD and the physiologic side effects of hot flushes and vaginal dryness associated with goserelin therapy.

Adolescent↗

PubMed1998

Intraoperative localization of small intestinal bleeding in an infant by methylene blue injection: a case report.

During the evaluation of patients with profuse gastrointestinal bleeding, it is often difficult to accurately localize bleeding sites in the small intestine. Moreover, during laparotomy, there may be no intraoperative findings to allow identification and resection of the bleeding lesion. Here the authors report a case of severe intestinal bleeding in an infant in whom the intraoperative injection of methylene blue dye into a terminal branch of the superior mesenteric artery was critical in determining the exact location of bleeding. After accurate localization of the bleeding source and segmental intestinal resection, the child recovered uneventfully with no recurrence of gastrointestinal bleeding. To the authors' knowledge, this is the first reported use of this technique in infancy.

Angiography↗

PubMed1998

Nucleotide sequence of the 4.3 kbp BamHI-N fragment of fowlpox virus FP9.

Nucleotide sequence analysis of the 4.3 kbp BamHI-N fragment of the fowlpox virus (FPV) genome revealed that it encodes 7 proteins with homology to vaccinia virus (VV) E11L, E10R, O1L, O3L, I1L, I2L and I3L encoded proteins. No evidence of FPV homolog of VV O2L could be found.

Amino Acid Sequence↗