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Biomedical subjects

S Olson

Publications and source records attributed to S Olson.

At least 19 recordsLinked to original sources
PubMed2002

Magnetic resonance imaging appearances of the uterus following microwave endometrial ablation.

AIM: Microwave endometrial ablation (MEA) is a treatment for dysfunctional uterine bleeding. It is a second generation ablative technique which is as effective as hysteroscopic methods but quicker and easier to perform. Our aim is to describe the Magnetic Resonance Imaging (MRI) appearances of the uterus following this procedure. METHODS: 15 women underwent MRI immediately before MEA, and again at one day and 4 months after treatment. T1 and T2 sequences were performed at 1.0T using a body coil. Images were assessed by 2 independent observers for quantitative and qualitative changes. Clinical questionnaires were completed before treatment and at 4 months. RESULTS: On images obtained one day post-ablation, 14 patients had a low signal intensity band subjacent to the treated area of the endometrial cavity on T2 images. Imaging at 4 months showed significant amounts of endometrial tissue in 11 patients, including 3 of the 6 patients who were amenorrhoeic. There were no changes in the appearances of myometrium or uterine dimensions and there were no haematometra. CONCLUSIONS: The detection of residual endometrium by MRI means that unopposed oestrogen hormone replacement therapy should be avoided after MEA, even in women who have amenorrhoea. Thepost-operative sub-endometrial low signal intensity zone corresponds to the region of tissue necrosis detected on vital staining of the treated uterus in in vivotesting. Depth of tissue destruction is a surrogate marker for clinical effectiveness. MRI may have a role in early assessment of patients participating in clinical research who are undergoing a modified MEA technique while retaining their uterus.

Cervix Uteri↗
PubMed2002

Spinal schistosomiasis.

A 23 year old female presented to Townsville General Hospital seven months after a positive urine test for Schistosomiasis with conus modularize signs. MRI confirmed a conus medullaris enhancing lesion. Serology was positive for Schistosoma IgG : IgM, 3.4 : 1.8. Urine screening for ova, stool sample, rectal biopsy and diagnostic investigations were negative. She was treated empirically for Schistosoma without biopsy with marked resolution of her symptoms and signs. She remains neurologically well one year after presentation. Serological identification from the Centre of Disease Control and Prevention in Atlanta Georgia by western blot has shown positive IgG for Schistosoma haematobium and mansoni. Schistosoma myelopathy is a rare cause of transverse myelitis, conus medullaris syndrome, anterior spinal artery occlusion and radiculopathy in Australia. It should however be included in the differential diagnosis in a patient who has been in or presenting from an endemic area.

Adult↗
PubMed2002

Acute subdural haematomas and enoxaparin.

Townsville General Hospital (TGH) has 285 beds and serves a population of approximately 500,0000 in North Queensland. In the period November 1998 until December 1999 there were three acute subdural haematomas (ASDH) related to therapeutic doses of enoxaparin. These culminated in death or severe neurological disability. Unfractionated heparin (UFH) is probably used equivalently in TGH. There were no intracranial haemorrhages in this period with UFH. It is well known low molecular weight heparins (LMWH) have a proven place in the management of deep vein thrombosis (DVT) and ischaemic heart disease (IHD). There may however be some concerns regarding the haemorrhagic complications of therapeutic doses of enoxaparin in the central nervous system.

Acute Disease↗
PubMed2001

Enzyme interactions in heparan sulfate biosynthesis: uronosyl 5-epimerase and 2-O-sulfotransferase interact in vivo.

The formation of heparan sulfate occurs within the lumen of the endoplasmic reticulum-Golgi complex-trans-Golgi network by the concerted action of several glycosyltransferases, an epimerase, and multiple sulfotransferases. In this report, we have examined the location and interaction of tagged forms of five of the biosynthetic enzymes: galactosyltransferase I and glucuronosyltransferase I, required for the formation of the linkage region, and GlcNAc N-deacetylase/N-sulfotransferase 1, uronosyl 5-epimerase, and uronosyl 2-O-sulfotransferase, the first three enzymes involved in the modification of the chains. All of the enzymes colocalized with the medial-Golgi marker alpha-mannosidase II. To study whether any of these enzymes interacted with each other, they were relocated to the endoplasmic reticulum (ER) by replacing their cytoplasmic N-terminal tails with an ER retention signal derived from the cytoplasmic domain of human invariant chain (p33). Relocating either galactosyltransferase I or glucuronosyltransferase I had no effect on the other's location or activity. However, relocating the epimerase to the ER caused a parallel redistribution of the 2-O-sulfotransferase. Transfected epimerase was also located in the ER in a cell mutant lacking the 2-O-sulfotransferase, but moved to the Golgi when the cells were transfected with 2-O-sulfotransferase cDNA. Epimerase activity was depressed in the mutant, but increased upon restoration of 2-O-sulfotransferase, suggesting that their physical association was required for both epimerase stability and translocation to the Golgi. These findings provide in vivo evidence for the formation of complexes among enzymes involved in heparan sulfate biosynthesis. The functional significance of these complexes may relate to the rapidity of heparan sulfate formation.

Animals↗
PubMed2001

The Fanconi anemia complementation group C gene product: structural evidence of multifunctionality.

The Fanconi anemia (FA) group C gene product (FANCC) functions to protect cells from cytotoxic and genotoxic effects of cross-linking agents. FANCC is also required for optimal activation of STAT1 in response to cytokine and growth factors and for suppressing cytokine-induced apoptosis by modulating the activity of double-stranded RNA-dependent protein kinase. Because not all FANCC mutations affect STAT1 activation, the hypothesis was considered that cross-linker resistance function of FANCC depends on structural elements that differ from those required for the cytokine signaling functions of FANCC. Structure-function studies were designed to test this notion. Six separate alanine-substituted mutations were generated in 3 highly conserved motifs of FANCC. All mutants complemented mitomycin C (MMC) hypersensitive phenotype of FA-C cells and corrected aberrant posttranslational activation of FANCD2 in FA-C mutant cells. However, 2 of the mutants, S249A and E251A, failed to correct defective STAT1 activation. FA-C lymphoblasts carrying these 2 mutants demonstrated a defect in recruitment of STAT1 to the interferon gamma (IFN-gamma) receptor and GST-fusion proteins bearing S249A and E251A mutations were less efficient binding partners for STAT1 in stimulated lymphoblasts. These same mutations failed to complement the characteristic hypersensitive apoptotic responses of FA-C cells to tumor necrosis factor-alpha (TNF-alpha) and IFN-gamma. Cells bearing a naturally occurring FANCC mutation (322delG) that preserves this conserved region showed normal STAT1 activation but remained hypersensitive to MMC. The conclusion is that a central highly conserved domain of FANCC is required for functional interaction with STAT1 and that structural elements required for STAT1-related functions differ from those required for genotoxic responses to cross-linking agents. Preservation of signaling capacity of cells bearing the del322G mutation may account for the reduced severity and later onset of bone marrow failure associated with this mutation.

Amino Acid Motifs↗
PubMed2001

Epithelial ovarian carcinoma and European birthplace of grandparents.

OBJECTIVE: The aim of this study was to determine whether the risk of ovarian carcinoma was related to latitude or to genetically based patterns of European geographic origin. PATIENTS AND METHODS: We studied the countries of origin of European-born grandparents of 168 newly diagnosed patients in two hospitals in New York City, compared with 159 controls from similar neighborhoods. We measured the risk of this cancer associated with having one or more white, non-Jewish grandparents born in North Europe versus none or in South Europe versus none. We also classified geographic origins in other ways to reflect the two main trends in genetic variations between Europeans mapped by Cavalli-Sforza et al. (The History and Geography of Human Genes, Princeton University Press, Princeton, 1994). Unconditional logistic regression was used to control for age, parity, years of use of oral contraception, age at menarche, education, Catholic religion, and area of residence and for numbers of Jewish grandparents, siblings, and first-degree relatives with breast or ovarian cancer. RESULTS: Approximately half of the subjects had least one white, non-Jewish grandparent born in Europe. There was no significant effect of ancestral latitude: among women born in the United States the odds ratio (OR) and 95% confidence limits associated with North European ancestry were 0.87 (0.47--1.63) compared with a reference group of women with no such ancestry. The corresponding OR for South Europe was 0.73 (0.39--1.74). Using the genetically based classifications of countries of origin, however, we found significant differences between cases and controls; ancestries from North West Europe and those from countries concentrically near Spain showed lower risks of ovarian carcinoma. CONCLUSIONS: The results support the hypothesis that the previously observed effects of latitude must act through environmental effects or through gene-environment interactions. Other variations in risk related to geographic origins are consistent with known patterns of genetic differences, but require confirmation in larger, population-based studies.

Adult↗
PubMed2001

Hepatic cryoablation-induced acute lung injury: histopathologic findings.

We have previously shown that hepatic cryoablation (cryo), but not partial hepatectomy, induces a systemic inflammatory response, with distant organ injury and overproduction of NF-kappaB-dependent cytokines. Serum tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2) levels are markedly increased 1 h and beyond after cryo compared with partial hepatectomy where no elevation occurs. NF-kappaB activation (by electrophoretic mobility shift assay) is strikingly increased in the noncryo liver (but not in the lung) at 30 min and in both the liver and lung tissue 1 h after cryo, returning to the baseline by 2 h and beyond. The current study investigated the histopathologic changes associated with cryoablation-induced acute lung injury. Animals underwent 35% hepatic resection or a similar volume hepatic cryo and were sacrificed at 1, 2, 6, and 24 h. Pulmonary histologic features were assessed using hematoxylin and eosin and immunoperoxidase staining with a macrophage-specific antibody (anti-lysozyme, 1:200 dilution, Dako, Carpinteria, CA). The following features were graded semiquantitatively (0-3): perivascular lymphoid cuffs, airspace edema and hemorrhage, margination of neutrophils within pulmonary vasculature, and the presence of macrophages with foamy cytoplasm in the pulmonary interstitium. Hepatic resection (n = 21) resulted in slight perivascular edema at 1, 2, 6, and 24 h post-resection, but there were no other significant changes. Pulmonary findings after hepatic cryo (n = 22) included prominent perivascular lymphoid cuffs 1 and 2 h following hepatic injury that were not present at any other time point (P 0.01). Marginating PMNs and foamy macrophages were more common after cryo at all time points (P<0.05, cryo vs resection). Severe lung injury, as evidenced by airspace edema and parenchymal hemorrhage, was present in four of six (67%) animals at 24 h (P 0.03). In follow-up studies immediate resection (n = 15) of the cryo-treated liver prior to thawing prevented the pulmonary changes. The findings of pulmonary perivascular interstitial macrophages 2 h following hepatic cryo suggests that hepatic cytokine production may induce downstream recruitment of pulmonary macrophages, which may contribute to subsequent severe lung injury. This study suggests that a soluble mediator from direct liver injury leads to neutrophilic lung inflammation and this is associated with the thawing phase of cryoablation.

Animals↗
PubMed2001

Positional cloning of a novel Fanconi anemia gene, FANCD2.

Fanconi anemia (FA) is a genetic disease with birth defects, bone marrow failure, and cancer susceptibility. To date, genes for five of the seven known complementation groups have been cloned. Complementation group D is heterogeneous, consisting of two distinct genes, FANCD1 and FANCD2. Here we report the positional cloning of FANCD2. The gene consists of 44 exons, encodes a novel 1451 amino acid nuclear protein, and has two protein isoforms. Similar to other FA proteins, the FANCD2 protein has no known functional domains, but unlike other known FA genes, FANCD2 is highly conserved in A. thaliana, C. elegans, and Drosophila. Retroviral transduction of the cloned FANCD2 cDNA into FA-D2 cells resulted in functional complementation of MMC sensitivity.

Alleles↗
PubMed2001

Intravenous infusion of a replication-selective adenovirus (ONYX-015) in cancer patients: safety, feasibility and biological activity.

Although genetically engineered adenoviruses hold promise for the treatment of cancer, clinical trial reports have utilized intratumoral injection to date. To determine the feasibility of intravenous delivery of ONYX-015, an E1B-55kD gene-deleted replication selective adenovirus with demonstrated clinical safety and antitumoral activity following intratumoral injection, we performed a clinical trial in patients with metastatic solid tumors. ONYX-015 was infused intravenously at escalating doses of 2 x 10(10) to 2 x 10(13) particles via weekly infusion within 21-day cycles in 10 patients with advanced carcinoma metastatic to the lung. No dose-limiting toxicity was identified. Mild to moderate fever, rigors and a dose-dependent transient transaminitis were the most common adverse events. Neutralizing antibody titers significantly increased within 3 weeks in all patients. IL-6, gamma-IFN, TNF-alpha and IL-10 increased within 24 h following treatment. Evidence of viral replication was detectable in three of four patients receiving ONYX-015 at doses > or = 2 x 10(12) particles and intratumoral replication was confirmed in one patient. In conclusion, intravenous infusion of ONYX-015 was well tolerated at doses up to 2 x 10(13) particles and infection of metastatic pulmonary sites with subsequent intratumoral viral replication was seen. The intravenous administration of genetically altered adenovirus is a feasible approach.

Adenocarcinoma↗
PubMed2001

Apocrine ductal carcinoma in situ of the breast: histologic classification and expression of biologic markers.

Apocrine ductal carcinoma in situ (ADCIS) has been called a special type of ductal carcinoma in situ (DCIS) because the histologic grading is considered difficult using the classification schemes that have been proposed for common DCIS. However, ADCIS encompasses a spectrum of lesions with different morphologic aspects ranging from minimally atypical to overtly malignant. To define a classification scheme for ADCIS, 35 cases (22 pure and 13 associated with invasive carcinoma) were selected on the basis of conventional morphology on hematoxylin and eosin (H&E)-stained sections. Each case was assigned to 1 of 3 histologic grades (low, intermediate, and high) based on nuclear morphology and the presence of necrosis. In addition, the expression of hormone receptors p53, bcl-2, c-erbB-2, and Ki-67 was evaluated by immunohistochemistry, and the DNA ploidy was determined by image cytometry. Fifteen cases were classified as high histologic grade, 10 as low histologic grade, and the other 10 as intermediate grade. All but 4 cases, irrespective of grade, had the same hormonal immunophenotype: androgen receptor positivity (97.1%) and estrogen receptor and progesterone receptor negativity (94.3% and 97.1% respectively). Twenty-one cases (61.8%) showed p53 expression, and 47.1% of the cases were positive for c-erbB-2. The median positivity for Ki-67 was 5.2%. ADCIS has a unique morphologic and hormonal profile, distinct from common DCIS, deserving a specific classification. The proposed classification scheme allows for categorization of ADCIS according to the most important morphologic features already seen in common DCIS, ie, nuclear grade and necrosis. The expression of biologic markers other than hormonal receptors and bcl2 in ADCIS seems in general to be similar to that in common DCIS. Ki-67 and c-erbB-2 are expressed more frequently in intermediate and high histologic grade ADCIS.

Adult↗
PubMed2001

Nutrition communication for a Latino community: formative research foundations.

Formative research techniques were used to develop a tailored health communication nutrition intervention for Latinas and their families. Members of the target community were recruited to participate in focus groups, depth interviews, and participant observations. Women, in particular, were observed preparing meals in their homes and purchasing groceries. The objective was to identify variables that could be used for targeting, segmenting, and tailoring the intervention. Results from these efforts were used to develop a theory-based intervention, which is described at the conclusion of the article.

Adult↗
PubMed2001

Fecal calprotectin: validation as a noninvasive measure of bowel inflammation in childhood inflammatory bowel disease.

BACKGROUND: Calprotectin is an abundant neutrophil protein, which is extremely stable in feces. This study aimed to validate fecal calprotectin as a marker of bowel inflammation against invasive measures in children with inflammatory bowel disease (IBD), including colitis and small bowel Crohn disease. METHODS: Fecal calprotectin was measured using a simple enzyme-linked immunosorbent assay in 36 spot stool samples from 22 children before colonoscopy and from 14 children before technetium-99 (99Tc) scanning. Using standard scoring systems, the severity of inflammation was assessed macroscopically and histologically at six standard sites in those who underwent colonoscopy and also at six standard sites in those who underwent 99Tc scanning. The subscores from each site were summated to give combined severity and extent scores for macroscopic and for histologic inflammation in the group undergoing colonoscopy and total inflammation in the group undergoing 99Tc scanning. RESULTS: In the 22 children who underwent colonoscopy, median fecal calprotectin was 4.9 mg/L (0.1-272.5 mg/L) (range). Disease groups included six normal cases, nine ulcerative colitis cases, two isolated Crohn colitis cases, two indeterminate colitis cases, and three allergic colitis cases. Fecal calprotectin correlated closely with colonic macroscopic inflammation (r = 0.75, P < 0.001) and histologic inflammation (r = 0.85, P < 0.001). Of the 14 children undergoing 99Tc scanning, 10 had Crohn disease, 3 had ulcerative colitis, and 1 had allergic colitis. Median fecal calprotectin was 9.1 mg/L (0.3-141.7 mg/L), and this correlated closely with the 99Tc scanning score (r = 0.80, P = 0.001). CONCLUSION: Fecal calprotectin correlates closely with the best invasive measures of colonic and small bowel inflammation in childhood inflammatory bowel disease. As a sensitive objective measure of bowel inflammation that is risk-free and noninvasive, fecal calprotectin lends itself particularly to the monitoring of and assessment of therapeutic interventions in children with inflammatory bowel disease.

Adolescent↗
PubMed2001

Preimplantation genetic diagnosis.

Preimplantation genetic diagnosis (PGD) has now been used in human fertility centers for a decade. To this end, diagnostic analysis is conducted on polar bodies or single blastomeres from biopsied embryos before the embryos are transferred, allowing the selection of normal embryos before a pregnancy has been established. Advances in technology available for PGD are described, including fluorescent in situ hybridization (FISH), interphase chromosome conversion, comparative genomic hybridization (CGH), fluorescent polymerase chain reaction (PCR), multiplex PCR, and whole genome amplification. These techniques support the diagnosis of a number of diseases at the single-cell level.

Chromosome Aberrations↗
PubMed2000

Enterocyte expression of interleukin 7 induces development of gammadelta T cells and Peyer's patches.

The intestinal mucosa is suggested to support extrathymic T cell development, particularly for T cell receptor (TCR)-gammadelta intraepithelial lymphocytes (IELs). TCR-gammadelta cell development requires interleukin (IL)-7; IL-7(-/)- or IL-7 receptor(-/)- mice lack TCR-gammadelta cells. Using the intestinal fatty acid binding protein (iFABP) promoter, we reinstated expression of IL-7 to mature enterocytes of IL-7(-/)- mice (iFABP-IL7). In iFABP-IL7 mice, TCR-gammadelta IELs were restored, as were cryptopatches and Peyer's patches. TCR-gammadelta cells remained absent from all other tissues. Likewise, T cell development in thymus and B cell maturation in the bone marrow and spleen retained the IL-7(-/)- phenotype. Thus, IL-7 expression by enterocytes was sufficient for extrathymic development of TCR-gammadelta cells in situ within the intestinal epithelium and was crucial for organization of mucosal lymphoid tissue.

Animals↗
PubMed2000

Soluble antigen and CD40 triggering are sufficient to induce primary and memory cytotoxic T cells.

The signals directing induction of tolerance rather than immunity are largely unknown. The CD8 T cell response to soluble Ags generally results in deletional tolerance following transient, costimulation-dependent activation. We demonstrated that CD40 signaling reversed the outcome of this response. Adoptive transfer of OVA-specific CD8 T cells followed by soluble OVA immunization resulted in induction of lytic activity and optimal clonal expansion only when CD40 was triggered via an agonistic mAb. Activation of CD8 T cells by CD40 signaling was indirect, because CD40 expression by host cells was required. CD40 signaling along with soluble Ag immunization also induced expansion of secondary lymphoid and intestinal mucosal endogenous OVA-specific CD8 T cells as detected by MHC tetramer reactivity. When CD40 activation was included, long-lived secondary lymphoid and mucosal memory CD8 cells were generated from adoptively transferred and endogenous CD8 T cells. Mucosal and peripheral CD8 memory cells exhibited constitutive Ag-specific lytic activity, with mucosal memory cells being 10-fold more lytic than splenic or lymph node memory cells. These results demonstrated that CD40 signaling during a response to a poorly immunogenic soluble Ag was necessary and sufficient for CTL and memory T cell induction.

Adoptive Transfer↗
PubMed2000

Computerized posturography analysis of progressive supranuclear palsy: a case-control comparison with Parkinson's disease and healthy controls.

BACKGROUND: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder that is frequently mistaken for Parkinson's disease (PD) in its early stages. OBJECTIVE: To compare balance measures using computerized posturography in patients with early PSP and early PD. METHODS: We performed computerized posturography (SMART Balance Master; NeuroCom International, Inc, Clackamas, Ore) in 20 patients with clinically diagnosed mild to moderate PSP (ambulatory) and compared results with those from 20 patients with PD of similar age and disease duration who were not receiving medications, and from 20 healthy age- and sex-matched controls. Sensory organization testing (SOT), limits of stability (LOS), and toes-up perturbations (4 degrees at 50 degrees per second) were tested while receiving and not receiving a combination of oral carbidopa (25 mg) and levodopa (250 mg) in the PSP group. Clinical assessment included Unified Parkinson's Disease Rating Scale, Performance-oriented assessments, and functional reach. RESULTS: When compared with the PD and control groups, total LOS time (P < .001) and path sway (P < .001) were significantly prolonged in PSP. Total SOT showed significantly worse scores in PSP compared with PD and control groups (F(2,57) = 29.6; P < .001). Univariate follow-up tests comparing PSP and PD showed differences in the following conditions: eyes open and visual sway (P = .003), eyes open and platform sway (P = .003), eyes closed and platform sway (P < .001), and eyes open and platform and visual sway (P < .001). Medium- and long-latency responses to perturbation were similar, but a larger number in the PSP group lacked short-latency responses (chi(2) = 11.3; P = .002). Levodopa administration did not significantly improve any aspect of posturography testing in PSP. In differentiating PSP from PD, LOS time and SOT condition of eyes open and platform and visual sway were nearly 100% sensitive and 100% specific (canonical correlation, 0.91). CONCLUSIONS: Computerized posturography testing reliably differentiated early PSP from early PD and age-matched controls. The PSP group demonstrated severely contracted limits of stability with probable deficits in motor programming. Results of SOT in PSP suggested a vestibular pattern and overreliance on visual cues, even when incorrect. The absence of short-latency responses (monosynaptic reflex arch) suggests an additional disturbance in the spinal cord or peripheral nervous system. Arch Neurol. 2000;57:1464-1469

Aged↗
PubMed2000

Expression of intestine-specific antigen reveals novel pathways of CD8 T cell tolerance induction.

Reactivity to intestinal epithelium-specific antigen was studied by transgenic expression of cytosolic ovalbumin controlled by an enterocyte-specific promoter. Transferred OVA-specific CD8 cells (OT-I) preferentially expanded in mucosal lymphoid tissues and the epithelium but failed to cause tissue damage. In contrast, concomitant VSV-ova infection induced OT-I-mediated epithelial cell destruction that correlated with antigen density. OT-I cells retained in the epithelium exhibited high levels of lytic activity but were unable to produce cytokines. The mice were systemically tolerant to OVA since endogenous CD8 cells were nonresponsive to VSV-ova infection. Thus, intestinal antigen gained access to peripheral tissues via absorption from effete epithelial cells. This system demonstrated a requirement for inflammation to drive pathogenic autoreactivity against enterocytes and identified pathways of intestine-specific immunoregulation.

Animals↗