Naive tumour-specific CD4+ T cells were efficiently primed in acute lymphoblastic leukaemia.

The recognition and neutralization of tumour cells is one of the big challenges in immunity. The immune system has to recognize syngeneic tumour cells and has to be primed and respond in an adequate manner. Priming of a leukaemia-specific immune response is a crucial step in tumour immunology that can mislead to tumour tolerance either by T cell ignorance, deletion or Treg induction. To resemble the situation of acute lymphoblastic leukaemia (ALL) in patients, we used the murine BALB/c model with syngeneic BM185 tumour cells. We established a tumour cell line that expresses the neo-antigen ovalbumin (BM185-OVA/GFP) to allow the application of T cell receptor transgenic, antigen-specific CD4(+) T cells. Here, we demonstrate that effective anti-ALL immunity can be established by in vivo priming of CD4(+) T cells that is sufficient to differentiate into effector cells. Yet they failed to control tumour alone, but initiated a Th1 response. An efficient tumour clearance was dependent on both antigen-specific CD4(+) T cells and CD8(+) effector T cells from the endogenous repertoire. The tolerogeneic milieu was characterized by increased Tregs numbers and elevated IL-10 level. Tregs hamper effective antitumour immune response, but their depletion did not result in reduced tumour growth. In contrast, neutralization of IL-10 improved median mouse survival. Future therapies should focus on establishing a strong CD4+ T cells response, either by adjuvant or by adoptive transfer.

Gene expression and immunohistochemistry in adipose tissue of HIV type 1-infected patients with nucleoside analogue reverse-transcriptase inhibitor-associated lipoatrophy.

BACKGROUND: Long-term use of both zidovudine (AZT) and stavudine (d4T) is associated with lipoatrophy, but it occurs possibly through different mechanisms. METHODS: Surgical biopsy specimens of subcutaneous adipose tissue were obtained from 18 human immunodeficiency virus type 1 (HIV-1)-infected lipoatrophic patients (the LA+ group) who were treated with either zidovudine (the AZT+LA+ group; n = 10) or stavudine (the d4T+LA+ group; n = 8) and from 10 nonlipoatrophic HIV-1-infected patients (the LA- group) who received antiretroviral therapy. Mitochondrial DNA (mtDNA) copy numbers, gene expression, and immunohistochemistry data were analyzed. RESULTS: mtDNA copy numbers were significantly reduced in the LA+ group, compared with the LA- group, and in the d4T+LA+ group, compared with the AZT+LA+ group. The ratio of mtDNA-encoded cytochrome COX3 to nuclear DNA-encoded COX4 expression was significantly lower in the LA+ group than in the LA- group. Compared with the LA- group, the LA+ group had significantly lower expression of genes involved in adipogenesis (SREBP1c and CEBPB), lipid (fatty acid synthase), and glucose (GLUT4) metabolism. Expression of genes involved in mitochondrial biogenesis (PGC1B), apoptosis (FAS), inflammation (IL1B), oxidative stress (PCNA and SOD1), and lamin B was significantly higher in the LA+ group than in the LA- group. The d4T+LA+ group had significantly lower expression of genes involved in mitochondrial biogenesis (POLG1), energy metabolism (the COX3/COX4 ratio), adipogenesis (SREBP1c and CEBPA), perilipin, and hexokinase than did the AZT+LA+ group. There were 7-fold more macrophages in adipose tissue specimens obtained from patients in the LA+ group, compared with the LA- group. CONCLUSIONS: Lipoatrophy is characterized by mtDNA depletion, inflammation, and signs of apoptosis. Changes were more profound in the d4T+LA+ group than in the AZT+LA+ group.

Aggregate characterisation by using the FlocFormer system to improve sludge dewatering.

In this paper, the influence of the polymer-induced flocculation on undigested sludge dewatering is investigated by image analysis. The mixing of flocculants in a so-called rapid-mixer and the subsequent forming of aggregates is carried out by the FlocFormer system, a new sludge conditioning system. For the mechanical dewatering a decanter device is used. To evaluate the efficiency of the dewatering process, the total solid content (TS) of the dewatered sludge is analysed. The results of this study show that this type of flocculation represents an alternative to improve sludge dewatering of undigested sludge. Compared with the standard conditioning (T-mixer), the FlocFormer leads to a better improvement (1.37 to 3.46%-points) in terms of TS while the rapid-mixer improves the dewatering efficiency only by 0.50 to 1.73%-points. Additionally, by using the FlocFormer conditioning, an optimal polymer dose of 5 g/kg TS has been detected. By increasing the polymer consumption (4-20% above the optimal dose) the dewatering efficiency remains practically constant (TS approximately 26.5%).

Detection of unstable carotid artery stenosis using MRI.

BACKGROUND AND PURPOSE: Carotid artery stenosis can be classified by magnetic resonance imaging (MRI) as lesion types I-VIII according to a modified histological scheme based on American Heart Association (AHA) guidelines. Lesion types IV-V and VI are regarded as high-risk plaques.We aimed to evaluate the clinical relevance of this classification for identifying unstable plaques. METHODS: Eighty-five patients (29 female) with severe carotid artery stenosis (diagnosed by Doppler and duplex ultrasonography) were imaged using a 1.5 T scanner with bilateral phased-array carotid coils. T1-, T2-, time-offlight (TOF) and proton-density (PD)-weighted studies were obtained. The carotid plaques were classified as lesion types III-VIII according to the MRI-modified AHA criteria. RESULTS: Thirty-five patients presented with a recently symptomatic stenosis; 50 patients were asymptomatic. Lesion types IV-V (51.4 % vs. 22 %) and VI (20 % vs. 4%; P < 0.0001) were found significantly more often in symptomatic patients compared to those without a history of cerebral ischemia. CONCLUSIONS: The distribution of lesion types differs significantly between symptomatic and asymptomatic carotid artery stenosis. High-risk lesion types IV-V and VI were overrepresented in recently symptomatic patients. MRI according to the modified AHA-criteria may be a suitable tool for detection of unstable carotid lesions.

The impact of sequential ozonation--aerobic treatment on the enhancement of sludge dewaterability.

Sludge ozonation processes have mostly been considered as regards the minimisation of the bio-solids while the improvement of sludge dewatering was more a welcoming side-effect. However, some papers announce a decrease of the dewatering efficiency by sludge ozonation. This indicates the presence of an optimisation potential, which is the subject of this study. Improvement of sludge dewaterability was found for an ozone dose which is much lower than that used for sludge minimisation. The repeated ozone and aerobic treatment allows further strong improvement of dewatering efficiencies. The key for this process optimisation is a well-balanced ozone dose related to the subsequent aerobic treatment time.

An overview of the integration of ozone systems in biological treatment steps.

Despite the well-known potential and performance of combined biological and ozonation processes for wastewater treatment, only few full-scale applications are published. Beside the synergistic effects of such process combination, which lead to oxidation of recalcitrant and inhibitory compounds or intermediates by enhancement of their biodegradability, the key for raising applicability is the improvement of the ozonation efficiency. An overview about the history and progress of full-scale applications, which deals with combined ozonation and biological treatment is given. Recently more than 40 applications exist, but many of them are not published. Therefore, a couple of selected not yet published applications have been mentioned in this paper. Landfill leachate and industrial wastewater treatment were mostly applicated, while treatment of municial wastewater treatment plant (WWTP) effluents are of increasing interest due to several advantages such as disinfection, decolourisation and removal of persistent dissolved organic carbon (DOC) for water re-use and groundwater recharge.

Do human osteoblasts grow into open-porous titanium?

A titanium foam for spine fusion and other applications was tested by cell culture. Its high porosity and surface roughness should enable bone cells to grow through it, resulting in a better fixation of the vertebral body. The foam was tested by in vitro experiments with human osteoblasts under static culture conditions and in a perfused system. By means of cell number, viability, scanning electron microscopy and histological staining, cell proliferation could be observed. The expression of osteogenic genes like collagen-I, alkaline phosphatase and osteocalcin was proven by reverse transcription polymerase chain reaction (RT-PCR) as well as in the case of alkaline phosphatase with biochemical methods. The conducted experiments showed that human osteoblasts could grow through the interconnected porosity of the metal foam and that they expressed an osteoblast like phenotype. The results suggest that in vivo osteoblasts are likely to form a trabecular bone bridge through this titanium foam. Consequently, with this osteoconductive material, there may be a reduced need for autologous bone in spinal fusion procedures.

[A telephone hotline as an easily accessible service for questions on schizophrenia]. / Telefon-Hotline als niederschwelliges Angebot für Fragen zur Schizophrenie.

Public relations activities of the German Research Network on Schizophrenia (GRNS) have shown that there is a demand for more information about schizophrenia disorder. This confirms international research findings that relatives of schizophrenia patients are particularly in need of information and support. In response, the GRNS has maintained a telephone hotline since 2001. The hotline is manned by clinical experts, psychiatrists, or psychologists once a week. The telephone calls are documented in a systematic manner. From 2001 to 2003, 3,909 calls were registered. This volume exceeds the limit of the hotline's resources. The telephone hotline is mainly used by relatives of psychotic patients. Most questions relate to the symptoms of schizophrenia and pharmaceutical treatment. The need for emotional support is also a high motivational factor for dialing the hotline number. The telephone hotline seems to be a worthwhile addition to the already existing crisis telephones and should be maintained even after public funding of the network expires.

[Diagnostics and therapy of depressive symptoms in schizophrenic patients]. / Bei Schizophreniepatienten immer abklären. Steckt hinter den Negativ-symptomen eine Depression?

The occurrence of depressive symptoms in schizophrenia is fairly common. In contrast to earlier assumptions, they usually have unfavorable consequences on the course of the disease. The response of depressive symptoms to therapy is well documented by empirical evidence and studies. In reality, however, the treatment of depressive symptoms in cases of schizophrenia occurs too rarely. This lack of medical treatment is partially explained by the clinicians' apprehension that antidepressive therapy could provoke a flare up of the psychosis. Nonetheless, this situation is often founded on the incorrect assessment of the depressive symptoms as negative symptoms that, in turn, are regarded by many clinicians as having limited treatability. In regards to this circumstance, a rethinking is desirable and, as a matter of principle, necessary.

Obsessive-compulsive disorder (OCD) with psychotic symptoms and response to treatment with SSRI.

The co-occurrence of obsessive-compulsive and psychotic symptoms in one patient often represents a diagnostic problem. Distinguishing among a schizophrenic disorder with comorbid obsessional symptoms, an OCD with comorbid psychotic symptoms, or an OCD and schizophrenia or any other psychotic disorder is of clinical importance, since the different diagnoses have different therapeutic as well as prognostic implications. In the following case report we describe a patient who suffered from a typical OCD for more than 18 years and then developed clear psychotic symptoms that completely remitted after treatment with citalopram.

Sludge treatment by ozonation--evaluation of full-scale results.

Ozonation of industrial and sewage sludge is a suitable process for minimizing the sludge production of activated sludge processes. The ozonation has the advantage for complete oxidation of volatile suspended solids (VSS) of combining partial sludge oxidation with subsequent biological oxidation. This paper describes the evaluation of two full-scale sewage sludge ozonation investigations for subsequent aerobic stabilisation as well as for subsequent anaerobic stabilisation compared to different sludge treatment processes. For both the anaerobic and aerobic application, sludge liquefying by release of 110 and 160 mg COD per g total suspended solids (TSS) has been reached at specific ozone consumption of 0.03 and 0.06 kg O3 per kg TSS, respectively. The subsequent biological treatment has reached a mass reduction of 20-35% for the aerobic and 19% for the anaerobic stabilisation. For both applications the specific ozone consumption was about 0.05 kgO3 per kg TSS to be treated. A comparison with mechanical and thermo-chemical sludge mass reduction methods shows that the mass reduction potential of ozonation is presently higher. Even though costs for sludge ozonation are higher compared to other methods, the optimisation potential for cost reduction of sludge ozonation is obvious from the results presented in this paper.

Advanced nitrogen elimination by encapsulated nitrifiers.

By introducing a mixed population of nitrifiers encapsulated in gel lens beads a more selective nitrification process was found in treatment of settled sewage in lab scale at a hydraulic retention time (HRT) of about 30 to 60 minutes. The reaction rates for oxidation of soluble chemical oxygen demand (SCOD) were found to vary between 25 to 150 mg/L x h while nitrification takes place around 50 mg nitrogen per hour and litre reaction volume. However, based on this SCOD removal in the nitrification step, a consequent post-denitrification process without nitrate recycle and dosage of external carbon sources has been proven to reach substantial nitrate elimination of up to 20 mg nitrogen per litre at COD/N-ratios of approx. 6 in settled sewage. At such COD/N-ratios, suitable nitrogen elimination seems to be possible, because the bioflocs of settled sewage, produced so far by SCOD oxidation and entrapment of particulate COD, are passing through the nitrification process having a substantial contribution to the denitrification rate additionally to the remaining SCOD.

Pre-nitrification by encapsulated nitrifiers--a possibility for self-sufficient energy operation of domestic WWTPs.

The overall energy consumption of domestic wastewater treatment plants (WWTPs) increases with treatment efficiency. Approximately 30 to 45 kWh per people equivalent and year is mostly necessary for advanced nitrogen and phosphorus removal, while the aeration contains the main part of approximately 60%. A new process using encapsulated nitrifiers on gel lens beads is introduced to overcome the high energy consumption of aeration. A more selective nitrification process was found at a nitrification rate of between 50 and 60 mg nitrogen per hour and litre reaction volume corresponding to a hydraulic retention time (HRT) of about 30 to 60 minutes while the soluble Chemical Oxygen Demand (COD) removal could be less than 30% depending on operational conditions of the bio-reactor. The latter enables internal use of wastewater's COD for a post denitrification. For the new process the energy consumption as well as total volume of bio-reactor are much less (approximately 30 to 50% for both) than conventional processes due to the low sludge age for COD and nitrate removal and the avoidance of internal wastewater recycle. Therefore, self-sufficient energy operation of domestic WWTPs operating with advanced treatment efficiency could become possible, if energy recovery by anaerobic sludge digestion is included.

Automation in sludge dewatering by novel on-line characterisation of flocculation.

A novel on-line method and system for characterisation of sludge flocs in view of improving sludge dewatering has been developed. The characterisation of sludge flocs was carried out after the conditioning or the flocculation process. The system uses a conventional CCD-line scan camera providing an on-line monitoring of the relative floc size distribution by image processing procedures. The image processing procedure has been re-evaluated and adapted to the practical dewatering results, obtained from a chamber filter press of 250 x 250 mm size. A good correlation between the calculated sensor signal and the sludge dewaterability of digested sludge in terms of the up-concentration factor was found. Although different sludge compositions and flocculation systems have been tested within the whole experimental period of six months, a good reproducibility of this correlation was also found. A well balanced floc size distribution is necessary showing that not too many but still some fine flocs and also not too large but compact flocs lead to improved dewaterability. This has been illustrated by an extended range of floc size measurements ranging between 50 microm and 29 mm. The conditioning monitoring system would be suitable for the control of production of good size-balanced flocs to compensate fluctuations in sludge characteristics of the sludge to be conditioned.

Ultrasound stimulation of micro-organisms for enhanced biodegradation.

An ultrasound (US)-assisted bioprocess for wastewater treatment for the food industry was developed in a three years EC-funded project (FAIR CT-3259). An improvement of biological activity by US was successfully demonstrated with lab scale reactors [Schläfer et al. Ultrasonics 38 (2000)]. Now a pilot scale optimisation with a 200 l bioreactor was carried out in co-operation with the Department of Industrial Acoustics, Technical University of Denmark and RESON A/S (Denmark). Batch experiments have been performed by measuring the degradation rate of organic compounds of wastewater. The process parameters were kept constant while varying the US-intensity. A significant increase of biological activity could be obtained only in a very narrow range of US-intensity. Very low US-power leads to a decrease of degradation rate down to the standard value if there is no US-intake. Implementation of too high level of US lead to drastically decreasing of the biological activity to a level far below the Standard value if there is no US-intake. The optimisation of this narrow US-power window needs to be carried out carefully for every investigated bioprocess. The most important aspect of the experimental results was that a more than 100% increase of the maximum biological degradation rate has been achieved by US-transduction with an optimum US-intensity of 1.5 W/l wastewater at 25 kHz. The developed bioprocess reduces the overall energy by use of low-energy US-irradiation below the cavitation level. The US-assisted biological degradation process would be presented together with its optimisation and the economical calculation.

Ultrasonic cell disruption of stabilised sludge with subsequent anaerobic digestion.

The world-wide increasing environmental awareness and its subsequent regulations have led to the application of improved technologies in wastewater purification plants. This has resulted in higher wastewater and sludge productions. Sludge is the by-product of such plants and it is not only rich in organic carbon and pathogens but also in heavy metals and other environmental pollutants. In Europe, agricultural application of dried sludge (bio-solids) is confronted with negative reactions from the citizens, governmental organisations, farmers and the food industry. Ultrasonic disruption of sludge is a popular mechanical disruption process in sludge treatment. During ultrasonic treatment, high frequency acoustic signals are used to initiate the cavitation process. The applied ultrasonic field leads to a breakdown of cohesive forces of the liquid molecules resulting in the generation of cavitation bubbles. A shock wave is released by the collapse of the cavitation bubbles and propagates in the surrounding medium forming jet streams that cause the disruption of cells in sludge. Disruption of sludge cells enables the release of light organic substances into the sludge water thereby exposing them for further anaerobic digestion. This paper presents results on the disruption of conventionally stabilised sludge through the application of the ultrasonic field. In order to reduce the specific energy input (i.e. ratio of the consumed energy during ultrasonic disruption to the input sludge mass) and improve biogas production, the total solids content of the stabilised sludge was increased before disruption. The anaerobic digestion of sludge samples was carried out in a set of specially constructed laboratory anaerobic digesters. Results showed that subsequent anaerobic digestion of the ultrasonically disrupted sludge could improve biogas production with reduced sludge quantity that is vital to the economic consideration of the wastewater treatment plants. This process encourages the exploitation of valuable materials and energy from stabilised sewage sludge just before its final disposal. The negative effects of mixing disrupted sludge with its separated sludge water are also shown in this paper. This expresses the microbiological instability of the anaerobic process caused by the mixing process.

Joint swelling as a predictor of death from cardiovascular disease in a population study of Pima Indians.

OBJECTIVE: Markers of inflammation have recently been shown to be predictive of cardiovascular disease (CVD). Furthermore, the excess mortality in rheumatoid arthritis (RA), a disease characterized by chronic polyarthritis, is chiefly due to death from CVD. With this background, we studied the effect of inflammation, as reflected by the number of joints with soft tissue swelling, and rheumatoid factor (RF) seropositivity on CVD-related mortality. METHODS: Mortality rates and rate ratios for all-cause and CVD-related deaths were computed in a longitudinal, population-based cohort of Pima Indians in Arizona from 1965 through 1994. Repeated health examinations were performed, involving systematic assessment of the features of RA, cardiovascular risk factors, serum titers of RF, as well as mortality. The cohort comprised 4,120 subjects (1,861 men, 2,259 women) who were examined an average of 3.5 times during a mean followup of 14 years. RESULTS: During the followup period, 182 CVD-related deaths ocurred. The age- and sex-adjusted CVD-related mortality rates increased significantly with the presence of a higher number of joints with soft tissue swelling (Ptrend = 0.04), and were 2.07 (95% confidence interval [95% CI] 1.30-3.31) times as high in those subjects who had 2 or more swollen joints as in those who had none. There were no significant additional effects on CVD-related mortality when seropositivity for RF or a previous diagnosis of RA were considered. In age- and sex-adjusted proportional hazards analyses, which were controlled for possible confounders, the effect of swollen joints remained significant (mortality rate ratio 1.33, 95% CI 1.04-1.71 per category increase [no swollen joints, 1 swollen joint, at least 2 swollen joints]). CONCLUSION: Joint swelling is a significant risk factor for CVD-related death, independent of other known risk factors including a diagnosis of RA. This finding supports the hypothesis that inflammatory mechanisms are important for the development of CVD.

Fibromyalgia-symptom or diagnosis: a definition of the position.

According to the American College of Rheumatology the diagnosis of fibromyalgia is based on criteria for the classification of fibromyalgia consisting entirely of clinical signs and symptoms. For diagnostic reasons autonomic disturbances and mental features have to be considered. The distinction between fibromyalgia (tender points) and myofascial pain syndrome (trigger points) is essential. Internal and neurological disorders as a primary cause of fibromyalgia have to be excluded. The etiology and pathogenesis of fibromyalgia still remain uncertain. The myopathological patterns in fibromyalgia are non-specific: type II fiber atrophy, an increase of lipid droplets, a slight proliferation of mitochondria, and a slightly elevated incidence of ragged red fibers. Initial reports on some allelic abnormalities in the serotonin system seem to highlight the important role of serotonin already presumed earlier. Significantly high levels of substance P in the cerebrospinal fluid of FM patients additionally support the impact of these neurotransmitters on both nociceptive and antinociceptive mechanisms.

Improvement of biological activity by low energy ultrasound assisted bioreactors.

Bioreactors are broadly applied in biotechnology and wastewater treatments. The so-called advanced bioreactor systems should be optimised in a more compact, more efficient and more effective form. One method of optimisation is the improvement of the solid-liquid interface of the sludge flocs and the mass transfer rate of gas and nutrients in the liquid. This could be obtained by the intake of ultrasound in the bioreactor at a frequency of 25 kHz and a power input of 0.3 Wl-1. An increase in the biological activity of the process investigated with alternating ultrasound as well as a decrease without ultrasound were measured.

Individual estimates of European genetic admixture associated with lower body-mass index, plasma glucose, and prevalence of type 2 diabetes in Pima Indians.

Individual genetic admixture estimates (IA) from European Americans (EAs) were computed in 7,996 members of the Gila River Indian Community (Arizona). Parental populations for the analysis were European Americans and full-heritage Pima Indians. A logistic regression was performed on 7,796 persons, to assess association of IA with type 2 diabetes. The odds ratio, comparing diabetes risk in full-heritage EAs with full-heritage Pima Indians, was 0.329 (95% confidence interval [CI] 0.225-0.482). Proportional-hazards analysis was performed on 5,482 persons who were nondiabetic at their first examination and 1,215 subjects who developed diabetes during the study. The hazard risk ratio for IA was 0.455 (95% CI 0.301-0.688). Nondiabetic persons had significantly more European IA. In nondiabetic Pimans, multivariate linear regressions of quantitative predictors of type 2 diabetes mellitus, including fasting plasma glucose, 2-h post-load plasma glucose, and body-mass index, showed significant inverse relations with IA when controlled for sex and age. These results illustrate the ongoing evolution of populations by the mechanism of gene flow and its effect on disease risk in the groups with admixture. When the two parental populations differ in disease prevalence, higher or lower risk is associated with admixture, depending on the origin of the admixed alleles and the relative magnitude of the disease prevalence in the parental populations. These data also illustrate the strong genetic components in type 2 diabetes and are consistent with one susceptibility locus common to obesity and diabetes.