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E Sievers

Publications and source records attributed to E Sievers.

At least 19 recordsLinked to original sources
PubMed2006

Activated gammadelta T cells express the natural cytotoxicity receptor natural killer p 44 and show cytotoxic activity against myeloma cells.

gammadelta T cells account for up to 10% of T lymphocytes in the peripheral blood of healthy donors. They can be activated by cytokines such as interleukin (IL)-2, IL-12 and IL-15, express natural killer (NK) cell markers such as NKG2D and show cytotoxic activity against several tumour cells, including multiple myeloma. Here, we present activated polyclonal gammadelta T cells from healthy donors with an NK T cell-like phenotype expressing the natural cytotoxicity receptor NKp44. Natural cytotoxicity receptors NKp30, NKp44 and NKp46 have been regarded as specific NK receptors; only two gammadelta T cell clones described so far expressed NKp 44. Isolated polyclonal gammadelta T cells cultured for 7 days according to the cytokine-induced killer cell (CIK) protocol with additional IL-15 revealed a surface expression of NKp44 of 8+/-7% (n=22). This could be confirmed by detection of NKp 44 mRNA by reverse transcription-polymerase chain reaction (RT-PCR). gammadelta T cells exhibited a marked cytotoxic activity against myeloma cells, which could be reduced by inhibition of NKp44. To our knowledge, this is the first description of the expression of NKp44 on polyclonal gammadelta T cells.

Cells, Cultured↗
PubMed2005

A recombinant anti-carcinoembryonic antigen immunoreceptor with combined CD3zeta-CD28 signalling targets T cells from colorectal cancer patients against their tumour cells.

BACKGROUND AND AIMS: The prognosis of metastatic colorectal cancer is still poor, raising the need for alternative therapeutic approaches, particularly by manipulating the antitumour immune response. Advanced tumour stages, however, are frequently accompanied by functional T cell defects which may be critical for a T cell based anticancer immunotherapy. The aim of this study was to address whether T cells from colorectal cancer patients with advanced tumour stages can be specifically antigen activated against their autologous tumour cells. METHODS: T cells were isolated from colorectal cancer patients and retrovirally transduced to express a recombinant immunoreceptor that has an extracellular binding domain for carcinoembryonic antigen (CEA) and an intracellular CD3zeta signalling domain with and without CD28 costimulation for T cell activation. RESULTS: Peripheral blood T cells from colorectal cancer patients were successfully engineered to express the anti-CEA immunoreceptor on the cell surface. On coincubation with autologous CEA(+) tumour cells, T cells with anti-CEA immunoreceptor are specifically activated to secrete interferon gamma (IFN-gamma) and to lyse autologous tumour cells whereas T cells without immunoreceptor are not. T cells equipped with combined CD3zeta-CD28 signalling receptor are more efficiently activated to secrete IFN-gamma compared with T cells with CD3zeta signalling receptor. Induction of interleukin 2 secretion on targeting towards autologous tumour cells requires triggering of T cells by the CD3zeta-CD28 costimulatory receptor. CONCLUSIONS: T cells from advanced colorectal cancer patients can be tumour specifically activated with high efficiency by engraftment with a combined CD3zeta-CD28 immunoreceptor to break tolerance against autologous tumour cells.

Aged↗
PubMed2005

Coculture with dendritic cells promotes proliferation but not cytotoxic activity of gamma/delta T cells.

T cells bearing the gamma9/delta2 T cell receptor (TCR) have recently raised interest as non-MHC restricted effector cells against multiple myeloma. They are described to be stimulated by phosphoantigens without the need of antigen presenting cells. However, in the past a positive effect of cells of the monocyte lineage on activation of gamma/delta T cells has been shown. Monocyte derived dendritic cells (DC) are professional antigen presenting cells widely investigated as stimulators of alpha/beta T cells. But only little is known about the interaction of gamma/delta T cells and monocyte derived DC. Here, we investigated the effect of coculture of mature DC unpulsed or pulsed with ibandronate on the proliferation and cytotoxic activity of isolated gamma/delta T cells. After coculturing monocyte derived DC with isolated gamma/delta T cells, proliferation of gamma/delta T cells was enhanced as determined by the (3)H thymidine uptake assay. Also, IFN-gamma secretion was increased after coculture with DC. As DC are well known to induce activation of alpha/beta T cells we investigated whether the cytotoxic activity of gamma/delta T cells could be increased by coculture with DC. We found no difference in cytotoxic activity of gamma/delta T cells alone or cocultured with unpulsed or pulsed mature DC. Also, sensitizing of myeloma cells by addition of ibandronate could not increase lysis by gamma/delta T cells. In conclusion, monocyte derived DC are capable of stimulating proliferation and secretion of IFN-gamma of gamma/delta T cells but do not exert an effect on cytotoxic activity of gamma/delta T cells against myeloma cells.

Cell Differentiation↗
PubMed2003

The impact of peripartum factors on the onset and duration of lactation.

Knowledge of peripartum indicators of those mother-infant pairs that are at increased risk of early failure of lactation may improve specific support of breastfeeding. Mode of delivery, labor complications, hyperbilirubinemia, milk intake and weight development were evaluated in healthy term infants in a hospital (n = 338). Delayed onset of lactation was observed in primiparae and in study participants with peripartum complications. The quantitative intake of human milk, assessed by test weighing 0-24 h and 24-48 h after the onset of lactation, was not significantly different between these groups. In addition, volume intake, weight gain and lactation success were tracked in 77 infants. Partial feeding of infant formula or an intake of <150 g of human milk per day 24-48 h after the onset of lactation was linked to weaning within 4 weeks. Ninety-one percent of the infants were exclusively breastfed at discharge; this value had declined to 49, 35 and 20% at 4, 12 and 20 weeks, respectively. Peripartum factors may contribute to early lactation failure; the long-term success of breastfeeding was predominantly determined outside the hospital.

Breast Feeding↗
PubMed2001

Molybdenum balance studies in premature male infants.

UNLABELLED: Despite the fact that the trace element molybdenum (Mo) is essential, there is insufficient knowledge about the demands in infancy. Mo balances were therefore assessed under consideration of formula Mo concentrations ranging from 0.125 to 2.704 micromol/l. Sixteen premature male infants participated in the investigation. Their birth weights were between 1,500 and 1,990 g, the median (range) gestational age was 34 (32-36) weeks and the post-conceptual age at the time of study 37.4 (34.1-40.6) weeks. Twenty-four balance studies were performed and the materials analysed by atomic absorption spectroscopy. Infants with a "low" Mo intake received 0.024 (0.020-0.035) micromol/ kg per day, had a urinary excretion of 0.02 (0.008-0.045) and a retention of 0.0006 (-0.03 to 0.008) micromol/kg per day. Infants with a "high" intake received 0.284 (0.227-0.487) micromol/kg per day, had a urinary excretion of 0.243 (0.118-0.378) and a retention of 0.022 (-71.1 to 141.44) micromol/kg per day. Since the median urinary excretion exceeded 60% of the Mo intake at low and high intakes, sufficient resorption but minimal retention was assessed at low intakes of Mo. CONCLUSION: In view of the limited knowledge of long-term exposure to an elevated molybdenum intake and the substantial retention observed at higher intakes, upper limits should be set for molybdenum concentrations in preterm infant formulas.

Humans↗
PubMed2001

Plasma selenium in preterm and term infants during the first 12 months of life.

The goal of the present study was to prospectively assess the plasma selenium (Se) concentrations of term and preterm infants during the first year of life in relation to gestational age and nutrition. Blood specimens were collected from orally formula-fed preterm infants (gestational age < 32 weeks, birth weight < 1500 g): 1.) in hospital and 2.) corrected for gestational age parallel to healthy term breast and formula-fed infants at the ages of 1, 4 and 12 months. All infants were fed according to a standardized nutritional concept, solids and follow-up formula were introduced at the age of 4 months. Plasma selenium in preterm infants in hospital was 11.7 (6.5-20.8) microg/l and 11.6 (8.8-16.7) microg/l at 4 weeks corrected for gestational age. At the age of 4 months plasma selenium was still significantly lower than in the other groups: Preterm infants: 17.1 (10.4-30.5) microg/l; formula-fed term infants: 31.3 (24.3-47.5) microg/l; breast-fed term infants: 45.6 (27.1-65.1) microg/l). The levels of breast-fed infants were significantly higher than those of both formula-fed groups up until the introduction of solids. Preterm infants had significantly low plasma selenium levels up until a postnatal age of at least 6 months. The levels were lower than those of term infants fed an identical unsupplemented infant formula during the first 4 months of life. These data support routine monitoring in hospital and selenium supplementation of preterm infants, preferably in hospital before discharge.

Gestational Age↗
PubMed2001

Molybdenum in infancy: methodical investigation of urinary excretion.

PROJECT: The clinical evaluation of trace element metabolism in infancy is based on optimal pre-analytical procedures. Urinary molybdenum excretion, the major determinant of its retention, was investigated to deduce criteria for representative specimen collection. PROCEDURES: 1.) Molybdenum concentration was analyzed in 24-hour urinary specimens (n = 193) to evaluate the range in pediatric patients. 2.) In 20 children aged 0.4 to 9.3 (mean 2.3) years admitted for a micturition cystourethrogram, three urinary collection methods (catheter, spontaneous midstream samples, urinary collection bags) were compared. 3.) Diurnal variations of molybdenum concentration were assessed by fractional urinary colLection in preterm infants fed infant formula or human milk (n = 10). Analysis was performed using atomic absorption spectroscopy. RESULTS: 1.) The molybdenum concentration in 24hour specimens was 4.0 (0-123) microg Mo/l. 2.) Urine gained by catheter collection (n = 20) rendered 7.0 (0.5-60.1) microg Mo/l, midstream samples and the use of urinary collection bags showed a concentration of 21.25 (0-91) microg Mo/l (p > 0.05). 3.) Fractional collection over 72 hours rendered a significant increase in only one participant. Diurnal differences of the urinary molybdenum concentration were significant between 3-6 p.m. and 6-9 p.m.. The molybdenum/creatinine quotient differed between the time intervals 3-6 p.m. and 9-12 p.m., as well as 9-12 a.m. and 6-9 a.m. (p < 0.05). CONCLUSION: Pediatric routine procedures are suitable for the assessment of urinary molybdenum excretion. The diurnal variations assessed are of minor clinical relevance, but should be considered by respective definition of collecting times and reference values.

Child↗
PubMed2001

Molybdenum metabolism: stable isotope studies in infancy.

The essential trace element molybdenum (Mo) is bound to and required for the function of molybdoenzymes, e.g. sulfite and xanthine oxidase. Dietary recommendations for early infancy are based on limited knowledge about its metabolism. 100Mo was used as an extrinsic tag to study the absorption and kinetics of excretion in infancy. 10 infants with a gestational age of 35 (30-39) weeks, a birth weight of 2.0 (0.9-2.3) kg and a post-natal age of 20 (10-54) days were studied. They received 25 microg 100Mo/kg with a feed of human milk or formula. Fractional urinary and fecal collections were conducted preceding the 100Mo intake and for 48-72 hours afterwards. The materials were analyzed by atomic absorption spectroscopy and inductively coupled plasma mass spectrometry. The median absorption of 100Mo intake was 97.5 (96.3 to 99.1) %. The retention of nutritive Mo intake and 100Mo in the study period was 11.2 (3.8-15.7) microg Mo/kg, equivalent to 35.7 (12.7-55.6) %. The Mo concentration increased to a peak value in urine within 8 (6-13) hours and in feces within 24 (7-48.5) hours. In addition, increases of copper in feces and urine were observed in 8 of 9 infants studied. Mo given orally is well resorbed in premature infants, and predominantly excreted in the urine. Dietary recommendations should prevent excessive intakes in infancy.

Copper↗
PubMed2001

Molybdenum in infancy: balance studies in patients with intestinal stomata.

UNLABELLED: This study investigated the supply of the essential trace element molybdenum (Mo) in infants with preternatural anus. It was divided into two separate investigations: (A) the complete fecal excretion of nine patients was collected in fractions over 24 h; and (B) 72 h balance studies and parallel plasma analysis were conducted in five infants and complemented by the longitudinal comparison of one of these patients with his (otherwise healthy) premature sister. Atomic absorption spectroscopy (balance studies) and high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS, plasma) were used for analysis. The following results were obtained. (A) The fecal Mo concentration ranged from 1.98 to 42.02 nmol Mo g(-1) dry fecal weight. (B) The daily intake in the balance studies was 43.2 (11.33-100.5) nmol Mo kg(-1) and the median retention was -2.91 (-32.45 to 48.6) nmol Mo kg(-1). In the premature twins the boy with an intestinal stoma had a negative balance and lost -3.32 micromol within 32 d, while his sister retained +0.45 micromol Mo in the same period. Plasma Mo ranged between 9.4 and 46.7 nmol l(-1). CONCLUSION: The negative Mo balance results may indicate an increased risk of Mo deficiency in infants requiring a long-term preternatural anus.

Anal Canal↗
PubMed2001

Molybdenum supply of very low-birth-weight premature infants during the first months of life.

This explorative study was performed to assess basic data on the Mo metabolism of premature infants. Premature (n = 18, gestational age < or = 32 wk, birth weight < or = 1,500 g) and healthy formula-fed term infants (n = 14) were nourished and corrected for gestational age, identically. Plasma was collected at 3, 16, and 52 wk and 72 h balances were performed at 3 wk of age. In the premature infants, these investigations were preceded by two balance studies and an initial plasma collection. Increased Mo intake and low relative urinary excretion resulted in a retention of 4.4 (0.99-7.77) microg Mo/kg initially in premature infants (median, range). Parallel plasma concentrations were 5.5 (2.5-7.3) microg Mo/L, declining to 2.36 (0.73-3.87) microg Mo/L at 4 wk. Term infants rendered 1.49 (0.29-1.7) microg Mo/L (p < 0.05), with no significant differences later. It was concluded that the supplementation of formulas for premature infants with Mo should be recinded until there is evidence for its necessity. Index Entries: Mo; premature infants; trace elements; formula; nutrition.

Food, Fortified↗
PubMed2000

Magnesium balance studies in premature and term infants.

BACKGROUND: The knowledge of magnesium requirements of premature infants is still very limited, although it is essential for the optimal composition of suitable formulas. AIM OF THE STUDY: The study concept was 1) to assess physiological magnesium balance data of healthy term infants and longitudinal results from formula-fed premature infants and 2) to deduce conclusions on the magnesium content of the formulas. METHODS: Premature infants (n = 14, birth weight < or = 1500 g, gestational age < or = 32 weeks) were studied in conventional balance trials with 1) a semi-elemental diet (A), 2) preterm infant formula (B), and 3) infant formula (C). In addition, healthy term formula-fed (n = 11, D) and breast-fed (n = 14, E) infants were investigated. Analysis was performed by flame atomic absorption spectroscopy. RESULTS: The median magnesium intake ranged between 4.84 mg/kg x d-1 (breast-fed infants) and 16.33 mg/kg x d-1 (premature infants). The term breast-fed infants retained nearly as much magnesium as term formula-fed infants (3.37 vs. 3.97 mg/kg x d-1), due to a low percental fecal and urinary excretion. A higher magnesium retention was observed in the premature group: A: 7.97 mg/kg x d-1, B: 5.3 mg/kg x d-1, 3.) C: 5.54 mg/kg x d-1. CONCLUSION: In view of the high percental magnesium retention in formula-fed premature infants, excessive supply should be avoided. The long-term effects of lower intakes have to be monitored.

Bottle Feeding↗
PubMed2000

Molybdenum supplementation in phenylketonuria diets: adequate in early infancy?

BACKGROUND: Molybdenum concentrations in formulas exceed those in human milk by far. Infants with phenylketonuria require semisynthetic phenylalanine-restricted diets. Because these diets are presently supplemented with molybdenum, a study was conducted to determine whether retention and plasma concentration in the recipients are equivalent to those of healthy breast-fed infants. METHODS: Balance and plasma studies were conducted in healthy breast-fed infants (n = 17) and in patients with phenylketonuria (n = 4) at the age of 4 weeks, and the plasma investigations were repeated at the ages of 4 and 12 months. The samples were analyzed by atomic absorption spectroscopy (balance studies) and high-resolution inductively coupled plasma mass spectrometry (plasma). RESULTS: Molybdenum intake and retention in all infants with phenylketonuria were more than 18 times those of breast-fed infants. The plasma concentrations reflected these differences. A median of 0.04 microg/l was assessed in breast-fed infants at 4 weeks and less than 0.02 microg/l at 4 months of age. Comparative results of infants with phenylketonuria were 2.9 microg/l and 2.5 microg/l, respectively. There were no significant differences between the groups at 12 months of age. CONCLUSIONS: The phenylketonuria diets investigated showed excessive retention and plasma concentrations of the essential trace element molybdenum in early infancy. In view of these findings, the present practice of molybdenum fortification should be revised.

Bottle Feeding↗
PubMed2000

New developments in the treatment of acute myeloid leukemia.

Curative therapy for acute myeloid leukemia (AML) remains unsatisfactory. However, three recent advances may play an important role in determining how AML is treated in the near future. First, the development of targeted antibody therapy using the anti-CD33-calicheamicin conjugate (gemtuzumab ozogamicin, Mylotarg) represents a novel targeted approach to the killing of leukemia cells. Second, modern molecular methods have improved our ability to identify minimal residual disease (MRD) in patients who appear to be in remission. These methods will allow physicians to tailor therapy, offering, for example, more intensive therapy to patients who harbor MRD. Lastly, the development of microarray gene expression technology allows for the simultaneous study of thousands of genes. With this technology, we may determine the genes responsible for the biological properties of treatment response and relapse in leukemia patients.

Aminoglycosides↗
PubMed1999

Influence of hyperfiltration on the measurement of urinary N-acetyl-beta-D-glucosaminidase.

The measurement of urinary enzymes in patients with diabetes mellitus has become a useful additional test for the early detection of nephropathy. Controversy persists concerning methods of measurement since during early stages of insulin-dependent diabetes mellitus children develop the so-called hyperfiltration syndrome. This study was performed to determine whether elevated levels of excreted creatinine influence the determination of the enzyme N-acetyl-beta-D-glucosaminidase (NAG). Reference values for NAG in single-spot urines (units NAG/mmol creatinine) and in 24-h collections (units NAG/l urine) were established in two different groups of 105 and 111 healthy children. NAG was then measured in single-spot urines (as NAG/mmol creatinine) and in collection urines of 30 diabetic children within the same 24-h period and compared with the reference population. These results were compared with hemoglobin (Hb)A1(a-c) and fructosamine values as well as creatinine clearance of the diabetic patients. There was a direct correlation between the NAG levels in single-spot and 24-h urine collections of diabetic patients. However, the NAG/creatinine ratio in the single-spot urines did not correlate with the HbA1(a-c) or fructosamine level. When 24 h collections (expressed as NAG/l) were used, the results correlated well with HbA1(a-c) and fructosamine. There was an inverse correlation between the creatinine clearance and the NAG/creatinine ratio, i.e., a high creatinine clearance correlated with a low NAG/creatinine ratio. This was not the case for 24 h collections (expressed as units/l). Hence, in children with insulin-dependent diabetes mellitus 24-h urine collections should be used for urinanalysis. Parameters should not be related to creatinine, since the ratio of urinary protein and creatinine is unreliable because of the high urinary creatinine during the hyperfiltration state.

Acetylglucosaminidase↗