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Biomedical subjects

A Mattsson

Publications and source records attributed to A Mattsson.

At least 19 recordsLinked to original sources

Rain events and their effect on effluent quality studied at a full scale activated sludge treatment plant.

The effect of rain events on effluent quality dynamics was studied at a full scale activated sludge wastewater treatment plant which has a process solution incorporating pre-denitrification in activated sludge with post-nitrification in trickling filters. The incoming wastewater flow varies significantly due to a combined sewer system. Changed flow conditions have an impact on the whole treatment process since the recirculation to the trickling filters is set by the hydraulic limitations of the secondary settlers. Apart from causing different hydraulic conditions in the plant, increased flow due to rain or snow-melting, changes the properties of the incoming wastewater which affects process performance and effluent quality, especially the particle removal efficiency. A comprehensive set of on-line and laboratory data were collected and analysed to assess the impact of rain events on the plant performance.

Nitrogen↗

Short circuiting in a denitrifying activated sludge tank.

The presence of a short circuit flow in a denitrifying activated sludge tank was identified and modelled. Tracer tests with pulse addition of lithium salt were used to investigate the hydraulics of the tank. The lithium concentration in the effluent was detected and residence time distribution (RTD) curves were generated. Hydraulic models based on completely stirred tank reactors (CSTRs) in series were generated from the RTD curves and the models were compared. The short circuit problem was successfully described using the Martin model, where the inflow is divided into two strands. Each strand was modelled as a number of CSTRs in series. At a normal flow the results of the model show that the tank has 12.8% dead volume, 85.8% main volume and 1.3% short circuiting volume. The inflow was divided into 91.9% entering the main volume and 8.1% entering the short circuiting volume. The mean velocity of the short circuiting stream was estimated to 0.4 m/s. At maximum flow the short circuiting stream was even larger and handled 24.3% of the flow. The short circuiting stream was identified in the upper part of the tank due to the position of the inlet and the outlet. The configuration of a tank including the use of baffles, the geometry of the inlet and mixer configuration should be considered carefully if short circuiting is to be avoided.

Bioreactors↗

Loss of cortical acetylcholine enhances amphetamine-induced locomotor activity.

Cholinergic disturbances have been implicated in schizophrenia. In a recent study we found that intracerebroventricular (i.c.v.) delivery of the immunotoxin 192 IgG-saporin, that effectively destroys cholinergic projections from the basal forebrain to hippocampus and cortex cerebri, leads to a marked facilitation of amphetamine-induced locomotor activity in adult rats. The aim of the present experiments was to evaluate the contribution of the septohippocampal versus the basalocortical cholinergic projections for the amphetamine hyper-response seen previously in i.c.v. 192 IgG-saporin injected rats. Since i.c.v. delivery of 192 IgG-saporin also destroys a population of Purkinje neurons in cerebellum, this cell loss needs to be taken into consideration as well. Cortex cerebri and hippocampus were selectively cholinergically denervated by intraparenchymal injections of 192 IgG-saporin into nucleus basalis magnocellularis and the medial septum/diagonal band of Broca, respectively. Selective loss of Purkinje cells in cerebellum was achieved by i.c.v. delivery of OX7 saporin. Possible effects of these three lesions on spontaneous and amphetamine-induced locomotor activity were assessed in locomotor activity cages. We find that selective cholinergic denervation of cortex cerebri, but not denervation of hippocampus or damage to cerebellum can elicit dopaminergic hyper-reactivity similar to that seen in previous i.c.v. 192 IgG-saporin experiments. Our data are compatible with the hypothesis that disturbances of cholinergic neurotransmission in cortex cerebri may be causally involved in forms of schizophrenia.

Acetylcholine↗

Cell cycle arrest of human gingival fibroblasts and periodontal ligament cells by Actinobacillus actinomycetemcomitans: involvement of the cytolethal distending toxin.

The cytolethal distending toxin (Cdt) is produced by several Gram-negative bacterial species and causes growth arrest and morphological alterations in mammalian cells. Actinobacillus actinomycetemcomitans, which is involved in the pathogenesis of localized aggressive periodontitis, also produces a Cdt that affects periodontal connective tissue cells. The aim of this study was to investigate in which phase of the cell cycle these cells are arrested and enlarged when challenged with A. actinomycetemcomitans, and to evaluate the involvement of its Cdt. Human gingival fibroblasts and periodontal ligament cells were challenged with A. actinomycetemcomitans extract, or with purified Cdt, and cell cycle analysis was performed by propidium iodide staining and flow cytometry. Cells exposed to an A. actinomycetemcomitans wild-type strain, or to purified Cdt, were arrested in both G1 and G2/M phases, and appeared enlarged compared to the corresponding controls. The cellular enlargement occurred in both G1 and G2/M arrested cells. In contrast, cells exposed to an A. actinomycetemcomitans cdt-knockout mutant strain showed cell cycle phase distribution and size similar to the controls. In conclusion, A. actinomycetemcomitans causes a combined G1 and G2/M growth arrest and enlargement in periodontal connective tissue cells, which is attributed to its Cdt.

Aggregatibacter actinomycetemcomitans↗

Reducing the total discharge from a large WWTP by separate treatment of primary effluent overflow.

At many large wastewater treatment plants (WWTPs) the increased hydraulic load, caused by combined sewer systems during storm events, results in primary effluent overflow when the capacity of further treatment is exceeded. Due to stringent effluent standards, regulating the total discharge from the WWTPs, the Rya WWTP in Göteborg and the Sjölunda WWTP in Malmö will have to reduce the impact of primary effluent overflow. Separate, high rate, precipitation processes operated only during high flow conditions have been investigated in pilot units at the two WWTPs. Precipitation in existing primary settlers operated at a surface loading of 3.75 m/h removed phosphorus to 0.35 mg/l. The Actiflo process was also shown to remove suspended solids and phosphorus well. BOD was reduced by 50-60%. With such processes the overall effluent concentrations from the plants can be reduced significantly. Key upgrading features are small footprints, short start up time and high efficiency.

Bioreactors↗

Excess breast cancer risk and the role of parity, age at first childbirth and exposure to radiation in infancy.

Exposure to ionizing radiation is a known risk factor for breast cancer and the fertility pattern is a recognized modifier of breast cancer risk. The aim of this study was to elucidate the interaction between these 2 factors. This study is based on a Swedish cohort of 17 202 women who had been irradiated for skin haemangiomas in infancy between 1920 and 1965. The mean age at treatment was 6 months and the median breast dose was 0.05 Gy (range 0-35.8 Gy). Follow-up information on vital status, parity, age at first childbirth and breast cancer incidence was retrieved through record linkage with national population registers for the period 1958-1995. Analyses of excess relative risk (ERR) models were performed using Poisson regression methods. In this cohort, the fertility pattern differed from that in the Swedish population, with significantly fewer childbirths overall and before 25 years of age but more childbirth after that age. There were 307 breast cancers in the cohort and the standardized incidence ratio (SIR) was 1.22 (95% CI 1.09-1.36). A linear dose-response model with stratification for fertility pattern and menopausal status resulted in the best fit of the data. ERR/Gy was 0.33 (95% CI 0.17-0.53). In absolute terms this means an excess of 2.1 and 5.4 cases per Gy per 10(4) breast-years in the age groups 40-49 and 50-59 years respectively. The fertility pattern influenced the breast cancer risk in this irradiated population in a similar way to that observed in other studies. SIR at dose = 0 was highest, 2.31, among postmenopausal nulliparous women (95% CI 1.48-3.40, n = 62). SIR at dose = 0 was lowest in pre- or postmenopausal women with a first childbirth before 25 years of age; 0.89 (0.71-1.09) and 0.88 (0.58-1.25) respectively. Thus, in addition to the dose-effect response in the cohort, part of the breast cancer excess could be explained by a different fertility pattern. The estimates of ERR/Gy for the various categories of age at first childbirth, number of children, menopausal status and ovarian dose were very similar, contradicting any interaction effects on the scale of relative risk.

Adult↗

Selective antibody-induced cholinergic cell and synapse loss produce sustained hippocampal and cortical hypometabolism with correlated cognitive deficits.

The physiological interrelationships between cognitive impairments, neurotransmitter loss, amyloid processing and energy metabolism changes in AD, cholinergic dementia and Down's syndrome are largely unknown to date. This report contains novel studies into the association between cognitive function and cerebral metabolism after long-term selective CNS cholinergic neuronal and synaptic loss in a rodent model. We measured local cerebral rates of glucose utilization ((14)C-2-deoxyglucose) throughout the brains of awake rats 4.5 months after bilateral intraventricular injections of a cholinotoxic antibody directed against the low-affinity NGF receptor (p75 NGF) associated with cholinergic neurons (192 IgG-saporin). Permanent cholinergic synapse loss was demonstrated by [(3)H]-vesamicol in vitro autoradiography defining presynaptic vesicular acetylcholine (ACh) transport sites. While other metabolic studies have defined acute and transient glucose use changes after relatively nonspecific lesions of anatomical regions containing cholinergic neurons, our results show sustained reductions in glucose utilization in brain regions impacted by cholinergic synapse loss, including frontal cortical and hippocampal regions, relative to glucose use levels in control rats. In the same animals, impaired cognitive spatial performance in a Morris water maze was correlated with reduced glucose use rates in the cortex and hippocampus at this time point, which is consistent with increased postmortem cortical and hippocampal amyloid precursor protein (APP) levels (45, 46). These results are consistent with the view of cholinergic influence over metabolism, APP processing, and cognition in the cortex and hippocampus.

Alzheimer Disease↗

Radiation risk and mammographic screening of women from 40 to 49 years of age: effect on breast cancer rates and years of life.

The aim of this study was to evaluate the carcinogenic risks associated with radiation in mass mammographic screening. Assessment was in terms of breast cancer mortality and years of life for a hypothetical cohort of 100 000 women. Data were obtained on incidence, mortality and life expectancy for the female population of Stockholm. With a screening interval of 18 months at ages 40-49 years, a total absorbed dose to the breast of 13 mGy per invited woman; and an annual breast cancer reduction of 25% per year 7 years from screening start, the net number of years gained was at least 2800. However, using the highest absorbed dose reported in routine mammographic screening in Sweden (approximately 3 mGy per view), and the highest reported radiation risk in the literature, a programme entailing annual screening with 2 views would require at least a 20% annual reduction in breast cancer mortality to give a net benefit in both the number of years of life gained and number of breast cancer deaths avoided. This observation supports the conclusion that exposures with low absorbed dose are essential when performing mass screening with mammography among young women.

Adult↗

Cognitive changes and modified processing of amyloid precursor protein in the cortical and hippocampal system after cholinergic synapse loss and muscarinic receptor activation.

A number of in vitro studies have shown that activation of muscarinic receptors by cholinergic agonists stimulates the nonamyloidogenic, alpha-secretase-processing pathway of amyloid precursor protein (APP). To determine whether increased cholinergic neurotransmission can modify the APP processing in vivo, we administered a muscarinic receptor agonist (RS86) to normal or aged rats and rats with severe basal forebrain cholinergic deficits (induced by 192 IgG-saporin). The levels of the cell-associated APP in neocortex, hippocampus, and striatum, as well as the secreted form of APP (APPs) in cerebrospinal fluid, were examined by Western blots. Additionally, we investigated the association between the altered APP levels and behavioral deficits caused by cholinergic lesions. We found that treatment with muscarinic receptor agonist resulted in decreased APP levels in neocortex and hippocampus and increased levels of APPs in cerebrospinal fluid. Regulation of APP processing by the muscarinic agonist treatment occurred not only in normal rats, but also in aged and cholinergic denervated rats that model this aspect of Alzheimer's disease. Interestingly, we found that elevation of APP in neocortex correlated with the cognitive deficits in water-maze testing of rats with cholinergic dysfunction. These data indicate that increased cholinergic neurotransmission can enhance nonamyloidogenic APP processing in intact and lesioned rats and that APP may be involved in cognitive performance.

Aging↗

Mortality after long-term exposure to radioactive Thorotrast: a forty-year follow-up survey in Sweden.

To evaluate temporal patterns of cause-specific mortality after long-term exposure to the alpha-particle-emitting contrast medium Thorotrast, we investigated a cohort consisting of 693 Swedish patients with neurological disorders who received Thorotrast during cerebral angiography, with follow-up ending in 1993. Standardized mortality ratios (SMRs) were calculated as the ratio of observed cases in the cohort to expected cases in the general population. Persons exposed to Thorotrast had significant excesses of all causes of death (SMR = 2.8; 95% CI 2.5-3.0), with similar increases noted for men and women. The largest risks were observed for deaths from hematological causes (SMR = 16.4; n = 8), cerebrovascular diseases (SMR = 10.1; n = 18), gastrointestinal disorders including liver cirrhosis (SMR = 5.2; n = 36), and tumors (SMR = 4.7; n = 187). There was a significant decrease in SMR with time since injection for cerebrovascular and circulatory diseases, indicative of the impact of underlying neurological disorders. In contrast, the SMR increased significantly with time for tumors and gastrointestinal diseases, suggestive of a detrimental effect of cumulative radiation dose. A significant dose-response relationship was found for all causes of death and malignant tumors among all age groups, and since SMR increased with time for the latter category, this is consistent with an effect of cumulative radiation exposure on cancer development. However, the findings should be treated with caution, since selection bias may have influenced some of the results.

Aged↗

Breast cancer risk after radiotherapy in infancy: a pooled analysis of two Swedish cohorts of 17,202 infants.

The incidence of breast cancer was studied in a cohort of 17,202 women irradiated for skin hemangioma in infancy at the Radiumhemmet, Stockholm, or the Sahlgrenska University Hospital, Gothenburg. A major part of the cohort had been treated with radium-226 applicators, and the mean absorbed dose to the breasts was 0.29 Gy (range <0.01-35.8 Gy). Two hundred forty-five breast cancers were diagnosed in the cohort during the period 1958-1993, and the standardized incidence ratio (SIR) was 1.20 (95% CI 1.06-1.36). Different dose-response models were tested, and a linear model gave the best fit. Neither age at exposure, breast dose rate, ovarian dose nor time since exposure had any statistically significant modifying effect, and breast dose was the only determinant of risk. The excess relative risk per gray (ERR/Gy) was 0.35 (95% CI 0.18-0.59), which is lower than in most other studies.

Adolescent↗

Induction of B cell responses in the stomach of Helicobacter pylori- infected subjects after oral cholera vaccination.

We have evaluated the possibility of inducing antibody responses locally in the human stomach as a prerequisite for the development of a vaccine against Helicobacter pylori. Both H. pylori-infected and noninfected subjects were immunized with an oral B subunit whole cell (BS-WC) cholera vaccine, and total and vaccine-specific antibody-secreting cells (ASC) were determined by the enzyme-linked immunospot (ELISPOT) technique in cells isolated from the antrum and duodenum, respectively, before and after vaccination. Most of the subjects responded to the vaccination with high frequencies of vaccine-specific ASCs in the duodenum as well as high-serum antibody titers, and no significant differences were seen in the responses between H. pylori- infected and noninfected subjects. When studying the gastric mucosa, on the other hand, there were dramatic differences between the H. pylori-infected and the noninfected subjects. Thus, whereas none of the noninfected subjects responded to the immunization in antrum, most of the H. pylori-infected subjects had high frequencies of vaccine-specific ASCs in this location after vaccination. Furthermore, the H. pylori-infected subjects had strikingly higher (as a mean 80-fold) frequencies of total IgA-secreting cells in antrum than the noninfected subjects, whereas the frequencies of total IgA-secreting cells in the duodenum were comparable between the groups. In conclusion, these results demonstrate the possibility of inducing antibody responses locally in the gastric mucosa of H. pylori-infected individuals, a finding with obvious implications for the future development of a therapeutic vaccine against H. pylori.

Administration, Oral↗

Outcome of treatment for ipsilateral breast tumor recurrence in early-stage breast cancer.

INTRODUCTION: The aims of the study were to assess the outcome among patients with early breast cancer operated on with wide local excision who developed a subsequent ipsilateral breast tumor recurrence, and to identify risk factors for uncontrolled local disease. Uncontrolled local disease (ULD) was defined as the appearance of clinically manifest invasive adenocarcinoma in the remaining breast or on the ipsilateral chest wall which could not be eradicated with salvage treatment during the period of follow-up (2-18 years). PATIENTS AND METHODS: Eighty-five patients in a cohort of 759 patients, treated for invasive Stage I-II breast cancer with breast-conserving surgery 1976-1985 in Stockholm, with a subsequent ipsilateral breast tumor recurrence (IBTR) were reviewed retrospectively. The majority of the patients were premenopausal (58%), node negative (72%), and had received postoperative radiotherapy (79%). Median follow-up time following breast-conserving surgery was 13 (9-19) years. Multivariate Cox's hazard regression was used in the statistical analysis to identify prognostic factors for ULD. RESULTS: The majority (n = 61) of the IBTR's were located in the original tumor quadrant and showed the same histopathological features as the primary tumor. Salvage mastectomy (n = 65) or reexcision (n = 14) were performed in 79 (93%) of the patients. Twenty-one patients developed ULD. Five years following the diagnosis of IBTR the disease-free survival was 59%, the cumulative incidence for ULD was 24%, and for death in breast cancer 34%. In the cohort of 759 patients, patients who received radiotherapy following the primary breast-conserving surgery had 1% cumulative incidence of ULD following the diagnosis of IBTR compared to 4% among patients that received no postoperative radiotherapy. The cumulative incidence at 5 years of ULD following salvage mastectomy was 12% compared to 33% after salvage reexcision. Patients operated on with breast-conserving surgery with an original tumor size < 15 mm, who were treated with salvage mastectomy for IBTR, had in multivariate analysis the lowest relative risk for ULD. Adjuvant chemotherapy following IBTR treatment did not seem to improve local tumor control. Following the diagnosis of IBTR, 78% (n = 21) of the patients with ULD and/or regional recurrence (n = 27), died of a disseminated breast cancer in contrast to 10% (n = 6) among the remaining 58 patients. CONCLUSION: Uncontrolled local disease is an important outcome measure following breast-conserving surgery. In this cohort, salvage mastectomy provided a superior local control rate compared to salvage reexcision. A higher although not statistically significant rate of ULD was also seen in patients who had not received postoperative radiotherapy as part of their primary treatment.

Antineoplastic Agents, Hormonal↗

Stereological estimates of nuclear volume in thin malignant melanomas.

Stereological estimation of nuclear volume was performed in a case control study of 72 malignant melanomas, thickness < or = 0.8 mm and Clark's level II-III. However, stereological measurements could be performed in only 57 thin melanomas due to too sparse cellularity. Thus, 21 thin metastasizing melanomas were individually compared with 33 thin non-metastasizing melanomas after individual matching of cases with one or two randomly chosen controls for site of primary tumour, tumour thickness, level of invasion, tumour regression and follow-up. Conditional logistic regression analysis showed no significant differences in nuclear volume between metastasizing and non-metastasizing thin malignant melanomas.

Cell Nucleus↗

Specific antibodies in sera and gastric aspirates of symptomatic and asymptomatic Helicobacter pylori-infected subjects.

In this study we have determined systemic and local antibody responses against different Helicobacter pylori antigens in H. pylori-infected and noninfected subjects. In addition, we studied whether differences in antibody responses between patients with duodenal ulcers and asymptomatic H. pylori carriers might explain the different outcomes of infection. Sera and in most instances gastric aspirates were collected from 19 duodenal ulcer patients, 15 asymptomatic H. pylori carriers, and 20 noninfected subjects and assayed for specific antibodies against different H. pylori antigens, i.e., whole membrane proteins (MP), lipopolysaccharides, flagellin, urease, the neuraminyllactose binding hemagglutinin HpaA, and a 26-kDa protein, by enzyme-linked immunosorbent assay. The H. pylori-infected subjects had significantly higher antibody titers against MP, flagellin, and urease in both sera and gastric aspirates compared with the noninfected subjects. Furthermore, the antibody titers against HpaA were significantly elevated in sera but not in gastric aspirates from the infected subjects. However, no differences in antibody titers against any of the tested antigens could be detected between the duodenal ulcer patients and the asymptomatic H. pylori carriers, either in sera or in gastric aspirates.

Adult↗

Antibody-secreting cells in the stomachs of symptomatic and asymptomatic Helicobacter pylori-infected subjects.

In this study we analyzed whether infection with Helicobacter pylori gives rise to specific B-cell responses against a number of putative virulence factors of H. pylori, e.g., urease, flagellin, and different bacterial surface antigens, locally in the gastric mucosa. This was studied in antrum and corpus biopsies collected from 11 H. pylori-infected patients with duodenal ulcers, 11 asymptomatic H. pylori carriers, and 13 noninfected, healthy controls. Mononuclear cells were isolated from the biopsies and assayed for frequencies of total and H. pylori-specific antibody-secreting cells (ASCs) by means of the enzyme-linked immunospot technique. The H. pylori-infected subjects had remarkably higher frequencies of total immunoglobulin A (IgA)- and IgM-secreting cells than the noninfected subjects, while the frequencies of IgG-secreting cells were virtually the same in the different groups. In addition, most of the infected subjects had IgA ASCs reacting with H. pylori membrane proteins, flagellin, and urease, while none of the noninfected subjects had any detectable H. pylori-reactive ASCs. Furthermore, half of the infected subjects also had ASCs reacting with a Helicobacter-specific 26-kDa protein, while only a few of them had ASCs reacting with neutrophil-activating protein, the neuraminyllactose-binding hemagglutinin HpaA, or lipopolysaccharides purified from different H. pylori strains. The frequencies of H. pylori-specific ASCs in the antrum and corpus were almost identical, and no differences in either antigen specificity or magnitude of the B-cell response in the stomach could be detected between the ulcer patients and the asymptomatic H. pylori carriers. This study demonstrates that H. pylori infection induces strong antibody responses in the human gastric mucosa, both in asymptomatic carriers and in duodenal ulcer patients. However, the outcome of infection could not be explained by differences in the local B-cell response to any of the antigens used in this study.

Adult↗

Human duodenogastric reflux, retroperistalsis, and MMC.

The aim of this study was to determine to what extent human migrating motor complex (MMC)-related secretory phenomena are influenced by a recently discovered period of duodenal retroperistalsis during late phase III. A constant-flow perfusion technique was used to measure gastric appearance of acid, bicarbonate, pepsin, bilirubin, IgA, and duodenally infused [14C]polyethylene glycol (PEG) 4000 in 12 healthy volunteers. Interdigestive gastroduodenal motility was recorded by digital manometry. During late antral phase II and III, the gastric lumen was acidified (P < 0.005 phase III vs. phase I) together with a marked increase in luminal pepsin output (3.1 +/- 1.2 during phase III vs. 0.25 +/- 0.08 kU/5 min in phase I, P < 0.01), followed by a realkalinization due to a simultaneous reduction of acid secretion and a duodenogastric reflux, aided by retrograde peristalsis, of bicarbonate and IgA but not of bilirubin, at the end of antral phase III (P < 0.05 phase III vs. phase I values). This physiological duodenoantral reflux phenomenon may play an important role in the chemical and immunological restitution of the antral mucosal barrier function after the exposure to high acid and pepsin concentrations during antral phase III activity.

Adult↗

Intracranial tumors after exposure to ionizing radiation during infancy: a pooled analysis of two Swedish cohorts of 28,008 infants with skin hemangioma.

The risk of intracranial tumors after exposure to ionizing radiation during infancy has been studied in a pooled analysis of two Swedish hemangioma cohorts (n = 28,008). The mean absorbed intracranial dose was low (7 cGy, range 0-11.5 Gy). The cohorts were followed up in the Swedish Cancer Register for incident intracranial tumors during the period 1958-1993. Eighty-eight tumors were found in 86 individuals compared to 60.72 expected [standardized incidence ratio (SIR) 1.42, 95% confidence interval (CI) 1.13-1.75]. The SIR increased significantly in ascending dose categories (P = 0.02). Dose-response analyses were performed with Poisson regression methods. There was a significant effect of dose, and the dose-effect relationship was negatively modified by age at first treatment. This indicates a higher risk for those exposed earlier in life. A linear dose-response model modified by age at first treatment resulted in the best fit. The excess relative risk (ERR) was 2.7/Gy (95% CI 1.0-5.6). The ERR/Gy was 4.5 if the treatment was given before 5 months of age, 1.5 if it was given at 5-7 months and 0.4 if it was given later. The study thus strongly indicates that there exists a dose-response relationship between absorbed dose in the brain and the subsequent risk of developing an intracranial tumor and that the risk is higher among infants exposed at younger ages.

Adult↗