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Biomedical subjects

U Keller

Publications and source records attributed to U Keller.

At least 37 records · Page 2Linked to original sources

High-power femtosecond fiber-feedback optical parametric oscillator based on periodically poled stoichiometric LiTaO3.

We demonstrate a synchronously pumped high-gain optical parametric oscillator with feedback through a fiber, using a passively mode-locked Yb:YAG thin-disk laser as a pump source. We obtain as much as 19-W average signal power at a wavelength of 1.45 microm in 840-fs pulses and 7.8 W of idler power at 3.57 microm. The repetition rate of the pulses is 56 MHz, and the transverse beam quality of the generated signal is M2 < 1.6.

Journal Article↗

Generation of 14.8-fs pulses in a spatially dispersed amplifier.

We demonstrate amplification and compression of 110-nm broad spectra in a spatially dispersed amplifier for what is believed to be the first time and generate 14.8-fs pulses with 450 microJ of energy at a repetition rate of 1 kHz. The amplifier concept is scalable in energy and allows for spectral shaping, which was demonstrated and compared with numerical simulations and showed excellent agreement.

Journal Article↗

Hypoglycemia in response to glucose and glucagon in insulinoma patients with a negative prolonged fast: functional and morphological properties.

A negative 72-h fast is usually considered to preclude the diagnosis of insulinoma. The aim of this study was to describe the functional and morphological properties of two exceptional patients with an insulinoma who had exhibited pre-operatively a negative 72-h fast. Despite the ability of tumor cells to turn off insulin secretion in response to low plasma glucose during 72 h of fasting, hyperinsulinemic hypoglycemia occurred in both patients in response to stimulation by classical secretagogues. Pre-operatively, both patients underwent oral and iv glucose challenge tests and iv glucagon stimulation test. Insulin secretion was rapidly stimulated by these secretagogues to an exaggerated extent and thereby caused hypoglycemia due to an insulin mass effect. In contrast to the common functional features during suppression and stimulation tests, the tumors differed widely with regard to insulin and proinsulin response to calcium during ASVS tests and morphological properties. In patient 1, the immunohistochemical proinsulin distribution pattern resembled that of normal beta-cells, i.e. the staining was restricted to the perinuclear area; insulin and proinsulin were not stimulated by calcium during the ASVS test. In patient 2, the proinsulin staining pattern was abnormal, i.e. proinsulin was also found in the periphery of tumor cells; insulin and proinsulin were stimulated by calcium. We conclude that normal or exaggerated rather than defective glucose sensing may explain hypoglycemia in these exceptional insulinoma patients. Different functional characteristics of these tumors can be correlated with distinct morphological properties.

Aged↗

Changes in bone mineral content after surgical treatment of morbid obesity.

Weight loss reduces bone mass and increases the risk of osteoporosis. This study was undertaken to assess changes of bone metabolism following Roux-en-Y gastric bypass (RYGB) and adjustable silicone gastric banding (ASGB) as compared to nonoperated controls of morbidly obese subjects. Fourteen female and 5 male patients with a mean (+/-SEM) age of 44.3 +/- 1.8 years participated in the 24-month prospective study. Nine patients underwent ASGB, 4 patients RYGB operation, and 6 patients were included in the control group. Bone metabolism was assessed by determination of serum parathyroid hormone (PTH), osteocalcin, urinary deoxypyridinoline, and dual energy x-ray absorptiometry (DXA) before, and 6, 12, and 24 months after intervention. The body mass index (BMI) decreased from 41.0 +/- 1.1 to 34.0 +/- 1.4 kg/m2 in the ASGB group (P = .001), from 42.7 +/- 2.2 to 30.5 +/- 2.2 kg/m2 in the RYGB group (P = .006), and remained unchanged in the control group (from 41.2 +/- 1.2 to 41.4 +/- 1.4 kg/m2) after 24 months. Bone mineral content (BMC) showed no significant change in the ASGB group (from 3,079 +/- 140 to 3,064 +/- 129 g) and in the control group (from 2,945 +/- 130 to 2,940 +/- 111 g), whereas it decreased from 2,968 +/- 111 to 2,621 +/- 139 g in the RYGB group (P = .005). The loss in BMC was accompanied by significant increases in urinary deoxypyridinoline (P < .05) and in serum osteocalcin (P < .01) after RYGB, suggesting both, increased bone resorption and increased bone formation. The authors were aware of the fact that the study groups were small and conclusions need to be regarded as preliminary. However, the RYGB operation resulted in enhanced weight loss and significant net loss of bone mass in comparison to ASGB and obese control subjects. Patients losing large amounts of body weight should be monitored regularly regarding prevention of osteoporosis.

Absorptiometry, Photon↗

Technical report. Radiation sensitivity testing by fluorescence in-situ hybridization: how many metaphases have to be analysed?

PURPOSE: The technique of three-colour fluorescence in-situ hybridization (FISH) is generally regarded as 'gold standard' for detecting chromosomal aberrations. The question was: how many metaphases should be counted to get reliable results? MATERIAL AND METHODS: Peripheral blood lymphocytes were irradiated in vitro (2.0 Gy). Metaphase chromosomes (1, 2, 4) were labelled by means of three-colour FISH and chromosomal aberrations (breaks per metaphase [B/M], complex chromosomal rearrangements per metaphase [CCR/M]) were analysed. To evaluate the correlation between the number of metaphases counted and the reliable detection of the rate of break events, B/M and CCR/M were scored using 250-1,000 metaphases in steps of 50 unirradiated cells, and from 50 to 200 metaphases in steps of 10 after 2 Gy. RESULTS: Analysing spontaneously occurring aberrations, B/M values based on 500 and 750 counted metaphases agreed well with those B/M values from 1,000 scored metaphases. After counting 150 metaphases after 2 Gy, the confidence interval of B/M values was about 44% smaller and the confidence interval of CCR/M values was about 41% smaller compared with values obtained after counting 100 metaphases. CONCLUSIONS: Scoring the number of spontaneous aberrations, reliable results can be obtained after counting 500 metaphases. After 2 Gy, a minimum of 150 metaphases should be analysed.

Chromosome Aberrations↗

[Effectiveness of therapeutic interventions in obesity].

Obesity is a chronic disease resulting from various genetic factors and environmental conditions (nutrition, sedentary life-style, psychological factors). The importance of prevention and therapy of obesity is emerging because of the high prevalence of metabolic complications. The first goal of any therapy must be a stabilisation of weight, followed by a reduction of body weight. Any intervention must be long-acting. Short-acting therapies (diets) result in a regain of body weight in over 90%. The most effective therapy is an integrative concept basing on: change of nutrition by reduction of fat and carbohydrate intake (daily deficit of 500-1000 kcal). psychotherapeutic approach, targeting a long-term change of eating-behaviour and life-style, avoiding guilt feelings. encouraging physical activity. Drugs (Orlistat, Sibutramin) may be helpful in selected cases as a part of a limited treatment, they do not replace changes in lifestyle. Surgical interventions (gastric banding, gastric bypass) can be considered in morbid obesity with the presence of metabolic complications, as they are the most effective way of weight reduction.

Behavior Therapy↗

Nonlinear femtosecond pulse compression at high average power levels by use of a large-mode-area holey fiber.

We demonstrate that nonlinear fiber compression is possible at unprecedented average power levels by use of a large-mode-area holey (microstructured) fiber and a passively mode-locked thin disk Yb:YAG laser operating at 1030 nm. We broaden the optical spectrum of the 810-fs pump pulses by nonlinear propagation in the fiber and remove the resultant chirp with a dispersive prism pair to achieve 18 W of average power in 33-fs pulses with a peak power of 12 MW and a repetition rate of 34 MHz. The output beam is nearly diffraction limited and is linearly polarized.

Journal Article↗

Generation of 3.8-fs pulses from adaptive compression of a cascaded hollow fiber supercontinuum.

We demonstrate generation of 3.8-fs pulses with energies of up to 15 microJ from a supercontinuum produced in two cascaded hollow fibers. Ultrabroadband dispersion compensation was achieved through a closed-loop combination of a spatial light modulator for adaptive pulse compression and spectral-phase interferometry for direct electric-field reconstruction (SPIDER) measurements as feedback signal.

Journal Article↗

The use of phage display to distinguish insulin autoantibody (IAA) from insulin antibody (IA) idiotypes.

AIM/HYPOTHESIS: Radiobinding assays (RBA) are unable to differentiate insulin autoantibodies (IAA) from insulin antibodies (IA). We sought to establish whether random peptide phage display might generate reagents with which to distinguish IAA idiotopes from IA idiotopes. METHODS: Two insulin-binding sera were used to select phagotopes from a phage library. The first, designated IAS, came from an insulin-treated patient with the insulin autoimmune syndrome, and was known to contain both IA and a high titre of human insulin specific (B30 threonine dependent) IAA. The second, designated IDD, was taken from a newly-diagnosed IAA(+) Type 1 diabetic patient. Phage colonies selected by insulin-purified IgG extracts of IAS and IDD were selected at random for DNA sequencing, and tested for their reactivity with insulin antibodies and ability to distinguish disease-associated idiotopes. RESULTS: Seven phagotopes bound IAS and the phagotope designated IAS-9, corresponding to sequence KRSRLDV, gave the highest binding standard deviation (SD) score. Seven phagotopes bound IDD and the phagotope designated IDD-10, corresponding to sequence LGRGGSK, bound most strongly. IAS-9 was able to displace insulin binding in IAS and all of ten insulin-treated Type 2 diabetic patients, but not the IAA present in any of the eight patients with newly-diagnosed Type 1 diabetes. IDD-10, on the other hand, could displace insulin binding detected in the sera of eight patients with untreated Type 1 diabetes (IAA), but not in IAS or sera of the insulin-treated Type 2 diabetics. CONCLUSION: Phagotopes provide reagents which between them can distinguish positively as well as negatively diabetes-associated IAA from non-diabetes associated IAA and from IA.

Amino Acid Sequence↗

60-W average power in 810-fs pulses from a thin-disk Yb:YAG laser.

We demonstrate a passively mode-locked diode-pumped thin-disk Yb:YAG laser generating 810-fs pulses at 1030 nm with as much as 60 W of average output power (without using an amplifier). At a pulse repetition rate of 34.3 MHz, the pulse energy is 1.75 microJ and the peak power is as high as 1.9 MW. The beam quality is close to the diffraction limit, with M2 < 1.1.

Journal Article↗

Single-shot kilohertz characterization of ultrashort pulses by spectral phase interferometry for direct electric-field reconstruction.

We describe a method of characterizing ultrashort optical pulses that is based on the technique of spectral phase interferometry for direct electric-field reconstruction and is capable of simultaneously measuring the amplitude and the phase of the electric field of a sub-10-fs pulse at kilohertz acquisition rates on a single-shot basis. Use of this technique results in a dramatic increase (>50x) in acquisition rate compared with that of existing diagnostics for full E-field characterization and opens the door to a range of new experiments in which shot-to-shot phase and amplitude fluctuations are studied at kilohertz rates.

Journal Article↗

Two-photon fluorescence excitation of macroscopic areas on planar waveguides.

In this paper, we report the first successful demonstration, to our knowledge, of two-photon fluorescence excitation (TPFE) using planar thin-film waveguide structures of macroscopic excitation dimensions (square millimeters to square centimeters in size). The high intensity of excitation light required for TPFE is available not only at a single focus point but along the whole trace of the beam guided in the waveguide structure. Line profiles of the fluorescence excited by TPFE show excellent correlation with the geometry of the launched laser beams. A clear second-order dependence of the fluorescence intensity on the excitation intensity confirms the two-photon character of fluorescence generation. Spectra of the emission generated by one-photon excitation and by two-photon excitation show only minor differences.

Equipment Design↗

Effects of changes in hydration on protein, glucose and lipid metabolism in man: impact on health.

Alterations of cell volume induced by changes of extracellular osmolality have been reported to regulate intracellular metabolic pathways. Hypo-osmotic cell swelling counteracts proteolysis and glycogen breakdown in the liver, whereas hyperosmotic cell shrinkage promotes protein breakdown, glycolysis and glycogenolysis. To investigate the effect of acute changes of extracellular osmolality on whole-body protein, glucose and lipid metabolism in vivo, we studied 10 male subjects during three conditions: (i) hyperosmolality was induced by fluid restriction and intravenous infusion of hypertonic NaCl (2-5%, wt/vol) during 17 h; (ii) hypo-osmolality was produced by intravenous administration of desmopressin, liberal water drinking and infusion of hypotonic saline (0.4%); and (iii) the iso-osmolality study comprised oral water intake ad libitum. Plasma osmolality increased from 285+/-1 to 296+/-1 mosm/kg (P<0.001 during hyperosmolality, and decreased from 286+/-1 to 265+/-1 mosm/kg during hypo-osmolality (P<0.001). Total body leucine flux ([1-(13)C]leucine infusion technique), reflecting whole-body protein breakdown, as well as whole-body leucine oxidation rate (irreversible loss of amino acids) decreased significantly during hypo-osmolality. The glucose metabolic clearance rate during hyperinsulinaemic-euglycemic clamping increased significantly less during hypo-osmolality than iso-osmolality, indicating diminished peripheral insulin sensitivity. Glycerol turnover (2-[(13)C]glycerol infusion technique), reflecting whole-body lipolysis, increased significantly during hypo-osmolar conditions. The results demonstrate that the metabolic adaptation to acute hypo-osmolality resembles that of acute fasting, that is, it results in protein sparing associated with increased lipolysis, ketogenesis and lipid oxidation and impaired insulin sensitivity of glucose metabolism.

Area Under Curve↗

Time-frequency characterization of femtosecond extreme ultraviolet pulses.

We present energy-resolved cross-correlation measurements of an extreme ultraviolet (XUV) pulse, generated as the fifth harmonic (15.5 eV) of an intense 80 fs laser pulse centered at 400 nm. Spectrally resolving the cross-correlation signal allows us to characterize the time-dependent frequency of the XUV pulse. We find that the fifth harmonic has a small negative chirp in excess of that predicted by perturbation theory. In addition, by manipulating the chirp of the driving laser we can induce and measure a positive or a negative chirp on the XUV pulse.

Journal Article↗

[From obesity to diabetes].

The major risk factor for the development of insulin resistance and type 2 diabetes is obesity. A key role is the new understanding of adipocytes as an endocrine system. Adipocytes secrete numerous substances that contribute to peripheral insulin resistance, including adiponectin, resistin, TNF-alpha and interleukin 6. There is also a role of free fatty acids by blocking directly intracellular metabolism of glucose and by their lipotoxicity. The pre-receptor metabolism of cortisol may be enhanced in visceral adipose tissue by activation of 11 beta-hydroxysteroid dehydrogenase type 1. The new class of thiazolidinediones (glitazones), binding to the peroxisome proliferator activated receptor (PPAR-gamma) lowers the levels of resistin and increases adiponectin, resulting in an improvement of glucose homeostasis. However, the first step to avoid insulin resistance should be an attempt to reduce body weight and to increase physical activity. These are successful means to avoid the development of type 2 diabetes from prediabetic states, as shown recently in 3 independent intervention trials.

Adipose Tissue↗