Feasibility of a fluorescent X-ray source for in vivo X-ray fluorescence measurements of kidney and liver cadmium.
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Biomedical subjects
Publications and source records attributed to M Olsson.
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In the management of coeliac disease, it has been widely accepted that oats must also be excluded from the diet, along with wheat, rye and barley. The article consists in a review of published reports, and an account of our experience of including oats in the gluten-free diets of adults. Oats were found to be safe and well tolerated by adults with coeliac disease and dermatitis herpetiformis, though the risk of wheat contamination of commercial oat products remains a cause of concern. Similar findings were reported from a study of adolescents, but no such studies have been made of small children. Thus, the inclusion of oats, known to be a fibre-rich, naturally gluten-free food, would broaden the range of foodstuffs tolerable to coeliac patients, though for safety reasons they should be used only by adults until more information is available.
Despite recent decrease in the incidence of Pneumocystis carinii pneumonia (PCP) among patients infected with HIV (human immunodeficiency virus), PCP remains a threat to other categories of immunocompromised patients. The article provides an outline of recent, mainly molecular genetic, findings in P. carinii research, including its new classification as a primitive fungus, host specificity and verified de novo infection in HIV-infected subjects. As the pathogen still defies propagation in vitro, laboratory diagnosis is dependent on microscopic demonstration of the organism. Diagnostic specificity can be enhanced by generating specific PCR (polymerase chain reaction) products which can be sequenced for genotyping. Findings in animal studies and epidemiological observations (e.g., in outbreaks of PCP among immunocompromised hospital patients), suggest transmission of PCP infection to be airborne. Genetic methods have been used to study the mode of P. carinii transmission. Nucleic acids of the human form of P. carinii (P. carinii f. sp. hominis) have been detected in the air of hospital wards, indicating susceptible patients to be at risk. By contrast, findings obtained with the same methods in studies of person-to-person transmission of P. carinii among clustered cases of PCP in hospitals suggest infection to be environmentally acquired. Thus, many questions remain to be answered regarding the occurrence and transmission of P. carinii infection.
BACKGROUND: Toxic deaths due to intensified treatment are of increasing concern in view of the generally improved prognosis for children with malignancies. Pneumocystis carinii pneumonia (PCP) during immunosuppressive treatment in children with malignancies is a severe complication with a poor prognosis if mechanical ventilation is required. Extracorporeal membrane oxygenation (ECMO) is a recognized technique that provides temporary respiratory support for patients with intractable respiratory failure. PROCEDURE: We here report successful ECMO support in four children with PCP, secondary to chemotherapy-induced immunosuppression, in whom the respiratory situation deteriorated despite pharmacological treatment and mechanical ventilation. The duration of ECMO was 7-43 days. RESULTS: Three children with acute lymphoblastic leukemia recovered from their PCP to continue chemotherapy and are now in complete continuous remission. Their pulmonary function normalized completely during 6-12 months after ECMO therapy. One child with a primitive neuroectodermal tumor survived the PCP and was off ECMO for 11 days before succumbing to unrelated complications. CONCLUSIONS: We conclude that ECMO offers an important means of respiratory support in children with severe PCP that can also be adopted during treatment for malignant disease.
In a relapse clinical trial patients who have recovered from some recurrent disease (e.g., ulcer or cancer) are examined at a number of predetermined times. A relapse can be detected either at one of these planned inspections or at a spontaneous visit initiated by the patient because of symptoms. In the first case the observations of the time to relapse, X, is interval-censored by two predetermined time-points. In the second case the upper endpoint of the interval is an observation of the time to symptoms, Y. To model the progression of the disease we use a partially observable Markov process. This approach results in a bivariate phase-type distribution for the joint distribution of (X, Y). It is a flexible model which contains several natural distributions for X, and allows the conditional distributions of the marginals to smoothly depend on each other. To estimate the distributions involved we develop an EM-algorithm. The estimation procedure is evaluated and compared with a non-parametric method in a couple of example based on simulated data.
BACKGROUND: Inflammation is known to be associated with enhanced nitric oxide production. A role for nitric oxide in coeliac disease has been suggested because of increased expression of the inducible isoform of nitric oxide synthase in the small intestine of patients with untreated coeliac disease. DESIGN: During small bowel endoscopy in 11 control subjects, 10 patients with untreated coeliac disease and seven patients with treated coeliac disease, gas was aspirated from different parts of the upper gastrointestinal tract and immediately analysed using a chemiluminescence technique. Luminal nitric oxide concentrations were also quantified in 13 control subjects who had undergone colonoscopy. RESULTS: Jejunal luminal nitric oxide concentrations were more than 20 times higher in patients with coeliac disease than in normal control subjects (mean 755 +/- 173 ppb, range 215-1690 ppb, vs. mean 31 +/- 9 ppb, range 1-83 ppb, P < 0.001). Jejunal luminal nitric oxide levels in patients with treated coeliac disease (mean 54 +/- 18 ppb, range 3-126 ppb) did not differ from those of control subjects. CONCLUSIONS: This study shows that intraluminal jejunal nitric oxide concentrations are significantly increased in patients with untreated active coeliac disease.
BACKGROUND: In embryonic kidneys, mesenchymal cells convert into epithelium in response to an induction by the tip of the ureter bud. Metanephric mesenchyme can also be induced to convert into epithelium in vitro. It is a model system to identify genes that could be important for epithelial development. METHODS: By differential screening of a cDNA library made from mesenchymes induced in transfilter cultures by embryonic spinal cord for 24 hours, we selected cDNA clones representing genes that were preferentially expressed in 24-hour-induced mesenchyme and not in uninduced mesenchyme. The sequence of one clone was determined and used to obtain the sequence of a complete open reading frame. By Northern blotting and in situ hybridization, the expression of the mRNA in embryonic kidneys was determined. RESULTS: We report the sequence and expression pattern of a marker for the 24-hour-induced state, mouse nuclear pore membrane glycoprotein 210 (mPOM210). The deduced 1886 amino acid sequence shows a 95% identity to the sequence of rat gp210. Northern blotting revealed a single 7.5 kb mRNA in 24-hour-induced mesenchyme, whereas message levels were fourfold to fivefold lower in uninduced mesenchyme. In situ hybridization of in vivo development confirmed the preferential expression of mPOM210 in epithelial cells. In the kidney, expression was seen in both the epithelium derived from the ureteric tree and the mesenchyme-derived epithelium. In other tissues of 13-day-old embryos, expression was also confined to the epithelium. In nervous tissues, the olfactory epithelium and walls of the lateral ventricle were the most prominently stained. Weak expression was seen in the heart. CONCLUSIONS: mPOM210 mRNA is an early marker for developing epithelial cells. Furthermore, our results suggest that nuclear pore membrane proteins could be more cell-type specific than previously anticipated.
The aim of the present study was to analyze if LDL particles trapped in stenotic aortic valve tissue undergo oxidative modification. Degenerative aortic stenosis affects >3% of the population >75 years of age in the Western world. Recent studies have revealed the presence of a chronic inflammatory process similar to what has been described in other degenerative diseases such as atherosclerosis. However, the underlying disease mechanisms of degenerative aortic stenosis still remain largely unknown. Six tricuspid stenotic valves, obtained at valve replacement, were compared with 3 control valves collected from hearts taken out during transplantation. The stenotic valves and the control valves were examined by immunohistochemistry, using antibodies against apoB, 4-hydroxynonenal-modified LDL, leukocytes, and HLA-DR. All valves were also stained with oil red O for neutral lipids. Extracellular neutral lipids were found in all stenotic valves, extending from the bases along the fibrosa layer. This lipid colocalized with apoB- and 4-hydroxynonenal-modified LDL immunoreactivity. 4-Hydroxynonenal-modified LDLs were present around calcium deposits, subendothelially, and in the deeper layer of the fibrosa. There was also a colocalization with macrophages, T lymphocytes, and HLA-DR expression. Control valves had a thin area of neutral lipid accumulation, a small amount of apoB, but no signs of inflammation. A distinct colocalization between oxidized LDLs, T-lymphocyte accumulation, and calcium deposits suggests that oxidized lipids may play a role in the disease process.
A small subgroup of patients accounts for a substantial proportion of emergency room (ER) consultations. Of the 479,956 consultations at ER facilities at Stockholm hospitals in 1996, a quarter were accounted for by six per cent of the patients, a subgroup characterised by at least four ER consultations during the year. Some 1,500 patients consulted 12-233 times. Analysis of the care-seeking habits of five extremely heavy ER-facility consumers showed them also to be heavy consumers of other health care services such as primary and tertiary facilities. Since previous studies have shown heavy ER-facility consumers to be a vulnerable subgroup both medically and socially, co-ordination and planning of their care might well be beneficial.
In order to investigate the accuracy and practicability of the polymerase chain reaction (PCR) in the antenatal diagnosis of congenital toxoplasmosis, a collaborative study involving 15 European laboratories was performed under the auspices of the Biomed 2 Programme of the European Community. Each team received 12 aliquots (four negative, eight positive) of 'artificial samples' made of amniotic fluid spiked with tachyzoites of the RH strain of Toxoplasma gondii. Each team performed its own PCR protocol (all were different). Nine of the 15 laboratories were able to detect a single parasite, but two of the 15 found all samples negative. Four of the 15 laboratories found one or more control samples to be falsely positive. This study highlights the lack of homogeneity between PCR protocols and performance and underlines the need for an external quality assurance scheme which could provide 'reference' samples that could be used by any laboratory wanting to establish and maintain an accurate diagnostic test based on PCR.
In vitro, epidermal growth factor (EGF)-responsive neural progenitor cells exhibit multipotent properties and can differentiate into both neurons and glia. Using an in utero xenotransplantation approach we examined the developmental potential of EGF-responsive cells derived from E14 mouse ganglionic eminences, cortical primordium, and ventral mesencephalon, after injection into the E15 rat forebrain ventricle. Cell cultures were established from control mice or from mice carrying the lacZ transgene under control of the promoters for nestin, glial fibrillary acidic protein (GFAP), or myelin basic protein (MBP). The grafted cells, visualized with mouse-specific markers or staining for the reporter gene product, displayed widespread incorporation into distinct forebrain and midbrain structures and differentiated predominantly into glial cells. The patterns of incorporation of cells from all three regions were very similar without preference for the homotopic brain areas. These results suggest that EGF-responsive progenitor cells can respond to host derived environmental cues, differentiate into cells with glial-like features, and become integrated in the developing recipient brain.
The time trend monitoring of organochlorine pollution was carried out in Sweden since the late 1960s. This report presents data on concentrations of DDT, PCB, HCHs and HCB in biota samples collected and analysed annually. All the matrices and compounds studied show a significant decrease over time. The data cover severely polluted Swedish marine and fresh water in southern Sweden as well as locally unpolluted waters in remote northern Arctic regions of Sweden. A total of 13 time series representing different locations and species are presented for the different pollutants. The period studied covers the time when pollution was serious as well as the time of recovery. All monitoring activities were carried out at the same laboratories over the entire study period, which means that comparability over time is good in the sets of data presented. The various time trends show a convincing agreement with trends and annual change over time, although the concentrations differ between the species and locations investigated, the highest concentrations being in the south. Since the annual changes are normally similar regardless of locations and species, spatial variations in concentrations remain over time, although concentrations are lower today. The onset of changes in concentrations over time can be related to international measures or other circumstances that lowered releases into the environment. Similarities in the annual changes, as well as the time when changes began, are discussed with respect to suggested hypotheses on the fate of the investigated organochlorines. It was not possible to verify that the oxygenation of anoxic sediments mobilised old pollution in Baltic sediments. Neither was it possible to conclude that eutrophication has caused a measurable effect on the rate and timing of the decreases. Finally, long-range transport to Arctic regions seems to be due more to a one step transport than to the 'Grass-hopper' effect. The comprehensive database used, clearly shows how important it is to have datasets big enough to describe between-year variation before attempting to evaluate the time trend. In addition, if between-year variation is not known, it is then also difficult to evaluate spatial variation on the basis of single year observations.
Cell fate determination and region-specific migration among neurons from the developing brain have been widely studied. Because similar attributes have been mostly unexplored in reference to glia, the present study has characterized the migratory responses of glia from diverse regions of the embryonic mouse brain after their transplantation to the brains of early postnatal (still developing) rats. Through the use of the mouse-specific, glial-specific marker M2, immunocytochemical processing of host tissues three to four weeks after transplantation revealed notable difference in the migratory patterns of phylogenetically diverse populations of glia. While glia from the ventral mesencephalon, cerebral cortex, and cerebellar neuroepithelium all showed a similar affinity for the nigropallidal tract after grafting to the internal capsule, only ventral mesencephalon-derived glia showed restricted migration toward and into the substantia nigra after transplantation to the thalamus or pontine tegmentum. These results suggest the presence of a highly favourable substrate for glial migration along developing fibre tracts, but, more importantly, indicates the potential for certain glia to respond to particular (region-specific) distal cues within the developing brain.
The striatum is thought to be generated from two transient swellings in the ventral telencephalon, the lateral and medial ganglionic eminences, present at mid-stages of embryonic rat development. We have studied the relative contribution of these structures to the specific generation of striatal neuronal subtypes such as projection neurons and cholinergic and somatostatin-containing interneurons at an early stage and a mid stage in striatal neurogenesis. Dissociated progenitors isolated from the embryonic day 12.5 and embryonic day 15.5 rat lateral ganglionic eminence grafted into the previously ibotenic acid lesioned adult striatum, produce grafts containing extensive numbers of neurons expressing messenger RNA for the striatal projection neuron marker, DARPP-32, whereas grafts of the embryonic day 12.5 and embryonic day 15.5 medial ganglionic eminences do not. While preprosomatostatin messenger RNA-expressing neurons were observed in grafts from each of the lateral ganglionic eminence and medial ganglionic eminence at both embryonic day 12.5 and embryonic day 15.5, choline acetyltransferase messenger RNA-expressing cholinergic neurons were largely found in grafts derived from the embryonic day 12.5 medial ganglionic eminence. These results suggest that the neuronal diversity of the adult striatum may derive both from the lateral ganglionic eminence, providing DARPP-32-expressing projection neurons as well as somatostatin-containing interneurons, and the early stage medial ganglionic eminence specifically contributing the cholinergic interneurons.
During development, telencephalic neural progenitors acquire positional specification and give rise to distinct structures such as the striatum and cortex. Here, we examine, in vivo, the influence of developmental stage, cell-surface molecules and regional differences along the dorso-ventral and antero-posterior axes on the selective incorporation of neural progenitors derived from different regions of the developing brain, utilizing a cross-species in utero transplantation paradigm. Striatal progenitors derived from the embryonic day (E) 12-14 mouse lateral ganglionic eminence (LGE) were observed consistently to incorporate into the developing striatum as early as 24-48 h following intraventricular injection into the E15-17 rat host. By removing cell-surface molecules from the LGE progenitors, the pattern of incorporation was remarkably different with no preferential striatal incorporation. Cortical progenitors with intact cell-surface molecules, by contrast, displayed little telencephalic (including striatal) incorporation as compared with precursors from the LGE. However, both progenitors from cortex and LGE incorporated widely into diencephalic and mesencephalic structures. The capacity for integration of precursors derived from the LGE and cortex gradually decreased during development of the host and was minimal in the postnatal day (P) 1 host. Unlike the telencephalic precursors, the vast majority of progenitors derived from the midbrain and cerebellar primordium (with cell-surface molecules intact) incorporated into diencephalic and midbrain nuclei with only a few cells observed in the telencephalon. These results demonstrate that incorporation of neural progenitors across the ventricular wall in the embryonic host is strictly developmentally regulated, dependent on their position along the antero-posterior axes and in the case of progenitors from the LGE is mediated by cell-surface molecules expressed on the transplanted cells.
Nerve growth factor (NGF) is a maintenance factor for cholinergic neurones in the brain, but its properties as a developmental survival factor are largely unknown. The low accessibility of the developing mammalian brain to experimental manipulation makes it difficult to increase NGF levels during the early phases of brain development. In the present study we have used an in utero, ex-vivo gene transfer approach to explore NGF actions during development of the cholinergic system in the rat brain. Significantly increased numbers of cholinergic neurones were found only in the mesopontine complex in animals receiving NGF-secreting transplants, whereas the cholinergic neurones in the basal forebrain and striatum were not clearly affected. The present results suggest that overexpression of NGF during development may promote the survival of distinct populations of central cholinergic neurones into adulthood.