Biomedical subjects

Jane E Dahlstrom

Publications and source records attributed to Jane E Dahlstrom.

11 recordsLinked to original sources

PubMed2006

CD8 T cells expressing killer Ig-like receptors and NKG2A are present in cord blood and express a more naïve phenotype than their counterparts in adult blood.

We report that natural killer receptors (NKR) for major histocompatibility complex (MHC) class I molecules (MHC-NKR), the inhibitory killer immunoglobulin-like receptors (KIR), and the CD94/NKG2A receptor are present on a small proportion of CD8 T cells in cord blood. On average, 1.67% of CD8 T cells in cord blood express KIR, and 0.74% expresses NKG2A, approximately fivefold less than in adult blood. CD8 T cells expressing MHC-NKR were present at similar levels in cord blood from preterm and term infants, and it is important that their presence was independent of placental pathology or infection. Cord blood CD8 T cells expressing MHC-NKR were relatively homogeneous and entirely CD27+, mostly CC chemokine receptor 7- and granzyme B-, with a majority being CD45RA+ and with no evidence for a skewed distribution of T cell receptor-Vbeta when tested in KIR+ cells. This contrasted with adult blood, which was more heterogeneous, and where a majority of CD8 T cells expressing MHC-NKR was CD27- and granzyme B+. Functional studies revealed that cord blood KIR+ CD8 T cells were as capable as KIR- CD8 T cells in their ability to proliferate in response to CD3 ligation, yet it is interesting that they were more capable than KIR- CD8 T cells in their ability to secrete interferon-gamma. These data suggest that cord blood CD8 T cells expressing MHC-NKR are a unique subset of cells, distinct from those in adult blood, and may represent a less-differentiated population.

Adult↗

PubMed2006

Placental assessment: simple techniques to enhance best practice.

BACKGROUND: The placenta provides a 'diary' of the pregnancy. The information provided from pathological assessment of the placenta may provide important clinical information for both the mother and the neonate. AIMS: To develop tools to ensure histopathological assessment of appropriate placentas and uniform provision of clinical history to pathologists to enable clinicopathological assessment. METHODS: A placenta information form was devised that included the following clinical criteria: gestational age, prolonged rupture of membranes at term, suspected maternal/fetal bacterial or viral infection, swabs taken for culture, intrauterine growth restriction, perinatal death, pre-eclampsia, essential hypertension, diabetes, placenta praevia, multiple pregnancy and cytogenetics. A table was introduced into the midwifery placenta policy indicating clinical criteria for microbiology, histopathological or cytogenetic assessment. A colourful reminder poster was designed and placed in the delivery suite and education sessions were provided. Six-month review periods were performed prior to and following the two interventions. RESULTS: The number of placentas submitted for histopathological examination (and meeting the inclusion criteria) increased from 41 (120/296) to 61% (161/266) following the initial interventions and to 82% (262/319) with the introduction of the reminder poster and education sessions. Clinically relevant placental pathology was found in 55 (64%) of cases in these time intervals. Comprehensive clinical history on the pathology report improved from 45 to 98% over the assessment time. CONCLUSIONS: Valuable information on a pregnancy can be provided by ensuring histopathological examination of appropriate placentas with the simple introduction of placental information sheets, updated midwifery policy, education sessions and a colourful reminder poster.

Benchmarking↗

PubMed2005

Antenatal steroids may reduce adverse neurological outcome following chorioamnionitis: neurodevelopmental outcome and chorioamnionitis in premature infants.

OBJECTIVE: To examine the effect of antenatal steroid exposure and in utero inflammation on the development of severe intraventricular haemorrhage, periventricular leukomalacia and long-term neurological outcome in infants less than 30 completed weeks gestation. METHOD: Infants less than 30 completed weeks gestation from January 1996 to July 2001 were identified from a prospectively managed database. Placental pathology was reviewed for the presence or absence of chorioamnionitis and funisitis. Infants were divided into three groups depending on the degree of exposure to fetal inflammation (no inflammation, chorioamnionitis only and chorioamnionitis and funisitis). Data relating to gestational age, birthweight, sex, antenatal steroid exposure, surfactant treatment, days of positive pressure ventilation and days of oxygen requirement were collected. Cerebral ultrasound studies were examined for evidence of intraventricular or intraparenchymal echodensity and periventricular leukomalacia. Long-term neurological outcome was assessed by neurological examination for cerebral palsy and by Griffiths Mental Developmental Assessment for general developmental quotient. RESULTS: Two hundred and twenty infants were identified. The mean gestational age was 27.7 weeks and the mean birthweight 1092 g. Seventy-two per cent of mothers had received a complete course of antenatal steroids. The risk of Grade III intraventricular haemorrhage or intraparenchymal echodensity was associated with exposure to in utero inflammation if a complete course of antenatal steroids had not been received (P = 0.002). This association did not exist if a complete course of antenatal steroids was given (P = 0.62). Fourteen infants had cerebral palsy (7%). The presence of cerebral palsy was also associated with in utero inflammation in the absence of complete antenatal steroid cover (P = 0.03) and not in the presence of complete cover (P = 0.59). The mean general developmental quotient on Griffiths Mental Developmental Assessment at 12 months or 3 years was not affected by exposure to in utero inflammation regardless of antenatal steroid exposure. CONCLUSION: Risk of intraventricular haemorrhage or intraparenchymal echodensity and cerebral palsy was associated with in utero inflammation in the absence of a complete course of antenatal steroids. A complete course of antenatal steroids appeared to extinguish any association between in utero inflammation and adverse neurological outcome.

Cerebral Palsy↗

PubMed2005

Surgical management of invasive breast cancer: a 5-year prospective study of treatment in the Australian Capital Territory and South-Eastern New South Wales.

BACKGROUND: Breast cancer is a major health problem in Australia. The aim of the present report is to evaluate the surgical management of invasive breast cancers in our region. METHODOLOGY: As part of a multidisciplinary quality assurance project, data were collected for the majority of breast cancers treated in our region between July 1997 and June 2002. Participants included surgeons, medical and radiation oncologists, pathologists and general practitioners. RESULTS: Over the 5-year period, 1069 invasive breast cancers were treated. Mastectomy (52%) was more common than breast conservation. For cancers less than 2 cm in diameter (61%), breast conservation was achieved in 62%. High nuclear grade cancers (27%) resulted in mastectomy in 60%. This treatment pattern was the same for patients living in urban and rural areas and in all age groups. Those patients requiring two or more operations (30%) to achieve surgical clearance still had a 33% rate of breast conservation. Over the last 5 years there has been an increase in sentinel node biopsies (16 sentinel node biopsies during 1998-1999; 64 during 2001-2002) and axillary dissections started to decrease. A small group has had no axillary node biopsy or dissection, mainly patients over 70 years of age. Multimodality treatments increased over the 5-year period of our study with the use of postoperative radiotherapy increasing from 60% to 65% and chemotherapy from 36% to 55%. CONCLUSIONS: The project has mapped treatment trends for breast cancer in our region and documented the implementation of new treatment methods as well as the increasing use of multidisciplinary management, multimodality treatment and the implementation of best practice guidelines.

Australian Capital Territory↗

PubMed2004

Mice deficient in glutathione transferase zeta/maleylacetoacetate isomerase exhibit a range of pathological changes and elevated expression of alpha, mu, and pi class glutathione transferases.

Glutathione transferase zeta (GSTZ1-1) is the major enzyme that catalyzes the metabolism of alpha-halo acids such as dichloroacetic acid, a carcinogenic contaminant of chlorinated water. GSTZ1-1 is identical with maleylacetoacetate isomerase, which catalyzes the penultimate step in the catabolic pathways for phenylalanine and tyrosine. In this study we have deleted the Gstz1 gene in BALB/c mice and characterized their phenotype. Gstz1(-/-) mice do not have demonstrable activity with maleylacetone and alpha-halo acid substrates, and other GSTs do not compensate for the loss of this enzyme. When fed a standard diet, the GSTZ1-1-deficient mice showed enlarged liver and kidneys as well as splenic atrophy. Light and electron microscopic examination revealed multifocal hepatitis and ultrastructural changes in the kidney. The addition of 3% (w/v) phenylalanine to the drinking water was lethal for young mice (<28 days old) and caused liver necrosis, macrovesicular steatosis, splenic atrophy, and a significant loss of circulating leukocytes in older surviving mice. GSTZ1-1-deficient mice showed constitutive induction of alpha, mu, and pi class GSTs as well as NAD(P)H:quinone oxidoreductase 1. The overall response is consistent with the chronic accumulation of a toxic metabolite(s). We detected the accumulation of succinylacetone in the serum of deficient mice but cannot exclude the possibility that maleylacetoacetate and maleylacetone may also accumulate.

Acetone↗

PubMed2004

Spitz naevus: diagnostic problems and their management implications.

Spitz naevus is an uncommon, benign melanocytic neoplasm that shares many clinical and histological features with melanoma. While Spitz naevi typically occur in children and melanomas typically occur in adults, either tumour can occur in a patient of any age. In cases displaying all or most of the classical histological features, particularly when occurring in a young patient, it is possible to make a confident diagnosis of Spitz naevus. However, for those lesions with atypical features it may be difficult to predict the biological behaviour with certainty from the histopathological appearance. Hence, such tumours have been referred to by a variety of names including atypical Spitz naevus, atypical Spitz tumour and spitzoid tumours of uncertain malignant potential. However, even acknowledged experts in dermatopathology have a low concordance in distinguishing Spitz naevus with atypical features from melanoma. In this article, we highlight the histopathological features of Spitz naevi and those that may be useful in distinguishing Spitz naevi from melanomas. A suggested practical guide to clinical management of such lesions is provided.

Adult↗

PubMed2003

Renal tubular dysgenesis and neonatal hemochromatosis without pulmonary hypoplasia.

Renal tubular dysgenesis is a rare disorder of differentiation of the fetal kidney. The condition has previously been reported as a postmortem diagnosis in infants who have had oligohydramnios commencing after 20 weeks gestation and have died of renal or respiratory failure shortly after birth with a clinical description of Potter sequence. The absence of clinically significant pulmonary hypoplasia in our case serves to emphasize that renal tubular dysgenesis, fetal anuria and long-standing oligohydramnios can occur without pulmonary insufficiency. The coexistence of renal tubular dysgenesis with neonatal hemochromatosis has been previously described in four published cases. The link between these two rare conditions is clinically important if dialysis or liver transplantation is considered in infants with hepatic and renal failure. Antemortem diagnosis by renal biopsy in our case enabled parental counseling and avoided the inappropriate use of peritoneal dialysis.

Adult↗

PubMed2003

Age-related pseudocapillarization of the human liver.

Age-related changes in liver function are important because they may promote susceptibility to adverse drug reactions, neurotoxicity, atherosclerosis, and other important diseases in older people. Age-related changes in the rat hepatic sinusoidal endothelium, termed pseudocapillarization, have been described recently and these may contribute to hepatic impairment. The present study has examined surgical and post-mortem specimens with immunohistochemistry and transmission electron microscopy to determine whether pseudocapillarization also occurs in older humans. The age of the subject, independent of systemic disease or hepatic pathology in surgical and post-mortem samples of human liver, was associated with increased peri-sinusoidal expression of von Willebrand's factor, collagen I, collagen IV, and staining with Masson's trichrome. Electron microscopy revealed significant age-related thickening of the sinusoidal endothelium (young 165 +/- 17 nm, middle age 222 +/- 11 nm, older 289 +/- 9 nm, p < 0.001) with loss of fenestrations (young 7.7 +/- 0.7 per 10 micro m, middle age 3.6 +/- 0.5 per 10 micro m, older 1.5 +/- 0.4 per 10 micro m, p < 0.001), and age-related deposition of basal lamina and collagen. In conclusion, ageing in humans is associated with morphological changes in the sinusoidal endothelium and space of Disse which are presumptively related to the ageing process and potentially represent an important link between the ageing process and disease susceptibility.

Adult↗

PubMed2003

Ultrastructural changes in hepatic sinusoidal endothelial cells acutely exposed to colloidal iron.

Hepatic sinusoidal endothelial cells form an important interface between the vascular system, represented by the sinusoids, and the space of Disse that surrounds the hepatocyte microvilli. This study aimed to assess the light microscopic and ultrastructural effects of acute exposure of hepatic sinusoidal endothelial cells to colloidal iron by injection of rats with iron polymaltose. Eight minutes after a single intravenous injection of iron polymaltose sinusoidal endothelial cells showed defenestration, and thickening and layering as assessed by transmission electron microscopy. Kupffer cells and stellate cells appeared activated. These changes were not observed in control animals, experiments using equivalent doses of maltose, or experiments using colloidal carbon except for Kupffer cell activation due to colloidal carbon. No significant light microscopic changes were seen in study or control animals. The findings indicate that acute exposure to colloidal iron causes changes in hepatic sinusoidal endothelial cells, stellate cells and Kupffer cells. This may be the result of a direct toxic effect of iron or increased production of reactive oxygen species. These observations suggest a possible mechanism for defenestration of sinusoidal endothelial cells in ageing and in disease states.

Animals↗

PubMed2002

Susceptibility of Msh2-deficient mice to inflammation-associated colorectal tumors.

Patients with longstanding extensive ulcerative colitis have an increased risk of developing colorectal cancer (CRC). There are significant differences in the early pathogenesis of colitis-associated tumors compared with common CRC, whereas the frequency, degree, and significance of microsatellite instability (MSI) as a marker of mismatch repair deficiency in colitis tumors remain unclear. Here we describe the application of the DSS model of chronic colitis to mice with a defect in the Msh2 mismatch repair gene to discern these early events. These mice do not develop CRC spontaneously without an external trigger. The aim of this study was to determine the effect of the Msh2 defect on the frequency and grade of colitis-associated colorectal dysplasia and adenocarcinoma in Msh2-/-, Msh2+/-, and wild-type (Msh2+/+) mice and on the MSI status of the tumors. We show that in mice with chronic colitis, 60% of the Msh2-/- and 29% of the wild-type mice developed high-grade dysplasia or adenocarcinoma, but heterozygosity for the Msh2 defect did not increase tumor susceptibility over wild-type genotype. The largest difference between genotypes was in the frequency of high-grade dysplasia, with 46.7, 8, and 12.5% in Msh2-/-, Msh2+/-, and Msh2+/+ mice, respectively. The Msh2-/- mice developed MSI-high tumors, whereas the majority of the Msh2+/- and wild-type tumors had no MSI. In the Msh2-/- mice, MSI appeared early in non-neoplastic colon tissue, presumably as a result of markedly increased epithelial cell proliferation associated with inflammation. These observations suggest that a homozygous mismatch repair defect predisposes to tumors triggered by chronic inflammation but is not the only factor involved because tumors also developed in the wild-type mice. This model of colitis offers opportunities to characterize the different molecular pathways of carcinogenesis operating in chronic colitis.

Adenocarcinoma↗

PubMed2002

The clinical significance of cytokeratin-positive cells in lymph nodes at the time of mastectomy from patients with ductal carcinoma-in-situ.

BACKGROUND: We determined the presence or absence of and clinical significance of cytokeratin-positive cells in the lymph nodes of patients who had had mastectomies for ductal carcinoma-in-situ. METHODS: Two pathologists independently assessed the axillary lymph nodes found. All patients had either a core or open biopsy performed before the time of mastectomy. The lymph nodes were assessed with hematoxylin and eosin stain and immunohistochemistry for cytokeratin marker AE1/AE3. The slides were assessed for the presence or absence of epithelial cells. As a control, axillary lymph nodes found in prophylactic mastectomies were assessed. None of these had had a previous biopsy performed. RESULTS: Lymph nodes from all patients demonstrated no obvious epithelial cells on hematoxylin and eosin stain. Peripheral sinuses of lymph nodes from six patients (23%) who had mastectomies for ductal carcinoma-in-situ contained a few cytokeratin-positive cells on immunohistochemistry. The lymph nodes of the control group demonstrated no cytokeratin-positive cells. The mean follow-up of patients was 5 years, and all patients were alive without recurrence at the time of the study. CONCLUSIONS: Epithelial cells may be present in the lymph nodes draining a site of recent breast biopsy in the absence of invasive carcinoma, indicating that these are an artifact of recent surgery and not of micrometastatic disease.

Adult↗