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Biomedical subjects

G Wilson

Publications and source records attributed to G Wilson.

At least 19 recordsLinked to original sources

Impact of cyclophosphamide on long-term reduction in sperm count in men treated with combination chemotherapy for Ewing and soft tissue sarcomas.

BACKGROUND: Treatment of cancer with multiple-drug chemotherapy regimens or radiation therapy can cause either temporary azoospermia of various durations or permanent azoospermia in young men. METHODS: To identify which drugs in which doses contribute to long-term or permanent azoospermia, semen analyses were done on patients with Ewing and soft tissue sarcomas before, during, and after treatment with either CYADIC (cyclophosphamide, doxorubicin, and dacarbazine), or CYVADIC (vincristine added to CYADIC). Some patients also received other drugs or radiation therapy. RESULTS: From pretreatment levels that were similar to those of control subjects, sperm production declined to azoospermia within 4 months of treatment. Sperm production returned in some patients after treatment; 40% of men recovered to normospermic levels by 5 years after treatment. Few patients showed continued recovery of sperm production after that time. The cumulative dose of cyclophosphamide was the most significant determinant of recovery to normospermic levels; approximately 70% of those who had received doses less than 7.5 g/m2 (median, 4.1 g/m2) recovered, but only 10% recovered when doses exceeded 7.5 g/m2. CONCLUSIONS: Thus, a risk of permanent sterility is associated with the use of the CYADIC and CYVADIC regimens in young men, especially when the cumulative dose of cyclophosphamide is greater than 7.5 mg/m2.

Adult

The effect of thrombin inhibitors on tissue plasminogen activator induced thrombolysis in a rat model.

Successful coronary thrombolysis depends on rapidly restoring blood flow and maintaining patency of the infarct-related artery. Although widely used as an adjunct to lytic therapy, heparin is limited in its ability to produce these effects. Since the limitations of heparin may reflect its inability to inactivate clot-bound thrombin, we developed a rat model of tissue plasminogen activator (t-PA) induced thrombolysis to compare doses of heparin, hirudin, hirulog (a synthetic hirudin-derived peptide), and D-Phe-Pro-ArgCH2Cl (PPACK) that produced a 4-fold prolongation of the baseline activated partial thromboplastin time (APTT) with saline in terms of their ability to accelerate thrombolysis and to prevent reocclusion. A thrombus rich in red cells and fibrin was formed in the distal aorta by applying an external constrictor after denuding the endothelium with a balloon catheter. Thrombolysis was induced with t-PA (1 mg/kg bolus, followed by 1 mg kg-1 h-1 over 30 min) and the rats were then randomized to receive a concomitant 80 min infusion of a thrombin inhibitor or saline. By continuously monitoring blood flow and pre- and post-stenotic blood pressures, the time to clot lysis, and the number of reocclusions were determined. Compared to saline, heparin had no significant effect on these variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Chloromethyl Ketones

Quantification of nucleic acids on nitrocellulose membranes with time-resolved fluorometry.

We use a streptavidin-based macromolecular complex (SBMC) labelled with the europium chelate of 4,7-bis (chlorosulfophenyl)-1,10-phenanthroline-2,9-dicarboxylic acid (BCPDA) as a staining reagent for biotinylated DNA present on nitrocellulose filters. The fluorescent spots or bands obtained can either be observed under UV illumination, photographed by instant camera photography or quantified by using a specially designed instrument working as a high resolution time-resolved fluorometric scanner. The detection limit is approximately 10 pg of target DNA. Various experiments with use of biotinylated DNA probes hybridized to Southern transferred targets have shown that the new procedure is a useful versatile non-isotopic methodology for staining DNA on solid supports.

Bacterial Proteins

Natural history of dilated cardiomyopathy in children.

To assess the natural history and potential risk factors in childhood dilated cardiomyopathy, we investigated 25 patients (ages 9.6 +/- 4.4 years) who presented after they were 2 years old. All patients had symptoms of congestive heart failure and reduced contractility with a dilated left ventricle at presentation. Two factors at presentation were significantly different between patients who died less than 1 year after the presentation (n = 14) and those who survived for more than 1 year (n = 9); cardiothoracic ratio (65.1% +/- 6.8% vs 57.1% +/- 6.1%, p less than 0.01) and left ventricular ejection fraction (31.3% +/- 7.0% vs 40.0% +/- 6.2%, p less than 0.05). Irrespective of intensive medical therapy, dilated cardiomyopathy in children had a poor prognosis; the actuarial survival rate was 41% at 1 year and 20% at 3 years. Other forms of therapy should be considered in the early stages of dilated cardiomyopathy in this high-risk group.

Cardiomyopathy, Dilated

Monoclonal antibodies to the major nonstructural nuclear protein of minute virus of mice.

Monoclonal antibodies were raised against a bacterial fusion protein containing amino acids 364 to 623 of the major nonstructural protein, NS-1, of minute virus of mice (MVMp), an autonomous parvovirus. By immunoblot analyses, these antibodies all recognized an 83-kDa protein in MVM-infected mouse fibroblast cells. Indirect immunofluorescence studies showed that five of the six react against a nuclear protein in MVM-infected mouse cells resulting in discrete foci of fluorescence. These foci do not correspond with the nucleoli, the site of MVM DNA replication. The epitopes of the antibodies were mapped using carboxy-terminal deleted bacterial fusion proteins derived from the plasmid encoding the original antigen and showed that four distinct epitopes were recognized by the different antibodies. A 25-amino-acid peptide was used in competition ELISAs to confirm the location of the epitope recognized by two antibodies CE10 and AC6. Preliminary characterization of an NS-1/NS-2 fusion protein synthesized in insect cells using a baculovirus expression vector showed that this fusion protein is also localized within the nucleus; however, in contrast, the full-length NS-1 polypeptide is located within the cytoplasm.

Amino Acid Sequence

Evaluation of two endotracheal suction regimes in babies ventilated for respiratory distress syndrome.

All low birthweight babies ventilated for the respiratory distress syndrome during a period of fourteen months were randomised to receive endotracheal suction 12-hourly or 6-hourly. There were no significant differences in respiratory outcome between the groups. These observations suggest that it is safe to aspirate endotracheal tubes infrequently during the first few days in uncomplicated respiratory distress syndrome.

Humans

Multiple epitopes of the human ovarian cancer antigen 14C1 recognised by human IgG antibodies: their potential in immunotherapy.

We have defined a novel ovarian cancer-associated membrane antigen, 14C1, using human monoclonal antibodies derived by EBV-transformation of in situ sensitised patients' B-cells. The pattern of recognition of this antigen by these antibodies suggests that at least three epitopes are discernable. These antibodies can be used to promote the in vitro killing of ovarian cancer cells by activated macrophages and cytokines, implying a role for this antigen in the immunotherapy of ovarian malignancies. Evidence is presented that the 14C1 antigen may have some transmembrane signalling function.

Adult

Relationship of cardiac size to maximal oxygen uptake and body size in men and women.

It has been suggested in previous studies that the difference in endurance performance between males and females is related to gender-specific differences in cardiac function. Other studies have not equated males and females for physical condition, and this may have contributed to the findings. The purpose of this study was to determine the extent to which the difference in VO2max in groups of similarly trained males and females was explained by gender differences in cardiac size, fat-free weight (FFW) and hemoglobin concentration [( Hb]). Measurements of VO2max, FFW, [Hb] and cardiac size (LVM) were made on 19 males and 20 females comparable in age and cardiorespiratory capacity. The difference between men and women in LVM accounted for 68.3% of the gender difference in VO2max, and the combination of LVM and FFW accounted for 98.7% of the gender-related difference in VO2max. It was concluded that the gender difference in LVM accounts for a majority of the difference in VO2max in males and females, with other aspects of body size accounting for nearly all the remaining difference. The gender difference in heart size primarily reflects the smaller overall dimensions of women.

Body Constitution

Improvement in oxygen tensions and pulmonary blood flow with intermittent distal aortic compression during normoxia, hypoxic hypoxia, and hyperoxia in neonatal piglets.

BACKGROUND AND METHODS: We investigated the hypothesis that, in a newborn piglet during normoxia, hypoxia, and hyperoxia, increasing aortic pressure transiently by intermittent short-duration aortic compression would affect left-to-right shunting of blood and thus increase pulmonary artery blood flow, pulmonary arterial PO2, and aortic PO2 proximal to the point of compression. We also investigated whether a balloon atrial septostomy, by providing an open channel for communication between the right- and left-sided circulations, would further improve pulmonary blood flow and aortic PO2. Studies were performed in eight 7- to 10-day-old newborn piglets in three phases (FIO2 of 0.21, 0.12, and 1.0) before and after balloon arterial septostomy in each piglet. Blood gas measurements and hemodynamic variables were recorded before and at the end of a 30-sec period of aortic compression. RESULTS: During aortic compression, all the animals demonstrated a 50 to 70 mm Hg increase in aortic pressure proximal to the compression. Before balloon septostomy, there were 21%, 41%, and 8% increases in aortic PO2 in the room air, hypoxic, and hyperoxic phases of the experiment, respectively. There were also statistically significant increments in pulmonary blood flow and arterial pressures. After balloon septostomy, there were 35%, 25%, and 21% increments in aortic PO2 during the room air, hypoxic, and hyperoxic phases of the experiment, respectively. However, there was no statistically significant further improvement in the effects of aortic compression on PO2 with septostomy compared with those effects before septostomy. CONCLUSIONS: Our results suggest that increasing systemic arterial pressures in order to forcibly affect left-to-right shunting of blood may be potentially beneficial in the management of hypoxia in situations where low pulmonary artery blood flow may be contributing to hypoxia, e.g., in persistent pulmonary hypertension of the newborn.

Animals

14C1, an antigen associated with human ovarian cancer, defined using a human IgG monoclonal antibody.

We have selected a human EBV-transformed cell line from the involved lymph nodes of an ovarian cancer patient which secretes an IgG1 kappa antibody, able to recognize an antigen present on the surface of ovarian cancer cells. The antigen, termed '14Cl,' has previously been shown by immunohistological techniques to be present on the surface of the malignant cells within tumour specimens. Western blotting analysis has shown that the majority of primary ovarian cancer specimens and three continuous cell lines derived therefrom express 14Cl; other tissue types were negative. Preliminary biochemical characterization has been carried out, which shows that the 14Cl antigen has a molecular weight range of 25-32 kD and an isoelectric point from pI 6.3 to 6.8. We believe that the 14Cl antigen is immunologically relevant to ovarian cancer patients and may therefore represent a novel target for both active and passive immunotherapy.

Antibodies, Monoclonal

Inflammatory pseudotumour of the urinary bladder.

An inflammatory pseudotumour that arose in the urinary bladder of a 33-year-old woman is reported. This is the twelfth reported example of this unusual non-neoplastic lesion that may be mistaken for a sarcoma. The lesion was composed predominantly of spindle cells that by routine light microscopical, ultrastructural and immunohistochemical examination had features consistent with myofibroblasts. Awareness of this unusual lesion is important to prevent its misinterpretation.

Adult

Primary health care: toward equity and efficiency in the accident and emergency department in Australia.

Primary health care in the accident and emergency department has been a philosophy of care that reacts to more than a client's presenting complaint (reactive care). It aims not only to manage the presenting complaint, but also to integrate continuing care with disease prevention and health promotion. Primary health care in the AED is intended to build fences around the cliffs forming our healthcare problems. At the same time it also encourages the provision of intensive care ambulances for those clients unfortunate to fall before the fences are finished or who fall over the fences.

Australia

Common factor 1 is a transcriptional activator which binds in the c-myc promoter, the skeletal alpha-actin promoter, and the immunoglobulin heavy-chain enhancer.

Ubiquitously expressed transcription factors play an integral role in establishing and regulating patterns of gene transcription. Common factor 1 (CF1) is a ubiquitously expressed DNA-binding protein previously identified in our laboratory. We show here that CF1 recognizes sites in several diverse transcription elements, and we demonstrate the ability of the c-myc CF1 site to activate transcription of a basal promoter in both B cells and fibroblasts.

Actins

N-myc genomic content and DNA ploidy in stage IVS neuroblastoma.

DNA ploidy and N-myc genomic content were analyzed in a series of stage IVS neuroblastomas by flow cytometry and Southern blot hybridization, respectively. Of the 12 stage IVS neuroblastomas studied, nine were aneuploid (DNA index [DI] greater than 1), two were diploid (DI = 1), and one was not assessable for DNA content due to insufficient tumor material. N-myc gene amplification was present in two of 12 tumors. None of the aneuploid tumors exhibited N-myc amplification. Among the aneuploid neuroblastomas, the DIs were between 1.27 and 1.60, ie, in the near-triploid range. The follow-up from diagnosis ranged from 1 to 41 months (mean, 20 months). The nine neuroblastomas with near-triploid DNA content were free of disease at the end of the follow-up period. In contrast, a rapid and fatal tumor progression was observed for the three neuroblastomas with N-myc amplification and/or diploidy. Although involving only a limited series, these results strongly suggest that the combined analysis of DNA ploidy and N-myc genomic content could predict clinical outcome in stage IVS neuroblastoma and should help to identify patients for whom a more aggressive therapy is required.

Aneuploidy

Williams syndrome in twins.

Two sets of identical twins with Williams syndrome have been reported previously. We report on 2 additional sets of presumed identical twins with Williams syndrome. All 4 patients had the typical Williams syndrome facial appearance, growth deficiency, and developmental delay. None of the patients had supravalvular aortic stenoses; however, all were diagnosed as having probable distal pulmonary artery stenosis. In the set of twins in which serum calcium was measured, one twin had an elevated serum ionized calcium level. These 2 sets of twins further document the occurrence of Williams syndrome in identical twins. To our knowledge, there are no reported cases of concordance in dizygotic twins. This adds further support to the likelihood that Williams syndrome is a genetic disorder.

Abnormalities, Multiple

The transport of vitamin B12 through polarized monolayers of Caco-2 cells.

Caco-2 cells grown on 0.45-micron filters, in Millicell chambers, form intact monolayers with many of the properties of polarized intestinal epithelial cells. It is reported here that these cells bind and internalize intrinsic factor-cobalamin complexes and that after 14-28 days in culture this specific binding is exclusively located on the apical membrane. Caco-2 cells also synthesize and secrete a protein with properties similar to transcobalamin II. This protein is secreted from the basolateral side of the cells after 20 days in culture. Specific apical-to-basolateral transcellular transport of [57Co]cobalamin also occurs between 20 and 28 days in culture. Thus, Caco-2 cells provide the first polarized human cell system for studying the transepithelial transport of cobalamin.

Biological Transport

Unsuspected diaphragmatic hernia: a potential cause of sudden and unexpected death in infancy and early childhood.

Congenital diaphragmatic hernias are usually found in neonates who present with respiratory distress. However, a significant number may remain clinically undiagnosed until much later in life. Of interest, the prognosis is felt to be better in this latter group. We describe three previously well patients (aged 2, 4, and 24 months) who suffered unexpected cardiorespiratory arrests due to unsuspected congenital diaphragmatic defects with intestinal herniation. Deaths resulted from cardiovascular and respiratory compromise due to visceral herniation that caused mediastinal and pulmonary compression.

Child, Preschool