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Biomedical subjects

S Berger

Publications and source records attributed to S Berger.

At least 55 records · Page 3Linked to original sources

Enrichment of spreadable fats with polyunsaturated fatty acids omega-3 using fish oil.

Polyunsaturated fatty acids of the omega-3 series, especially very long chain--eicosapenta- and docosahexaenoic acid (EPA, DHA)--exert a strongly desirable influence on health. However, their intake with the western-style diet is usually too low which favours development of many diseases (CVD, cancers, allergies, etc.). Nowadays elevation of EPA and DHA intake is commonly recommended, but almost the only dietary source of them is seafoods, especially fish. A new way to increase the intake of long-chain omega-3 without radical changes of eating patterns is enrichment of regularly consumed foods with unhydrogenated fish oil. The aim of this study was to establish sensory and nutritionally acceptable enrichment level of low-calorie spreadable fats (soft margarine and mix of butter and vegetable oil) with EPA and DHA by addition of fish oil preparations (ROPUFA--30% EPA, DHA and MARITEX--10%), and evaluation of the stability of enriched spreads during storage (sensory and chemical). It was shown that tested spreadable fats might be enriched up to 1% EPA, DHA (i.e. 3% ROPUFA, 8% MARITEX), and that this had no significant influence on sensory acceptability. Both used fish oils which exerted similar influence on the quality of fats. An enriched mix of butter and vegetable oil and margarine may be stored up to 3 and 6 weeks respectively without significant decrease of quality. Peroxide value and acid numbers were not much affected by enrichment and storage. Daily portion (25-30 g/day) of spreadable fats enriched on the level established in the study may provide 0.2-0.3 g EPA, DHA, significantly increasing the amount of long-chain omega-3 in the diet above those eaten normally.

Animals↗

Detection of firearm imprints on the hands of suspects: effectiveness of PDT reaction.

Pyridyldiphenyl triazine (PDT) and three of its analogues were compared as practical reagents for visualizing unseen impressions left on the hands of a person who has held a firearm. The parent compound, PDT, gave the best results using intensity and clarity as measuring criteria. The effectiveness of the PDT reaction was then studied on 147 volunteers who had held firearms in their hands. Identifiable impressions of the metallic parts of the weapons were developed on the hands of 103 volunteers (70%). Results with females were slightly higher than with males, however, the difference was possibly statistically insignificant, and needs further study. Ferroprint and Ferrotrace, 5 commercial preparations that are based on the PDT reaction, have become a part of the professional equipment of every crime scene technician in Israel.

Adult↗

[Present role of continuous subcutaneous insulin infusion (CSII) by insulin pump in the treatment of diabetes mellitus].

Since the publication of the DCCT results, intensive insulin treatment, including continuous subcutaneous insulin infusion (CSII), has been considered one of the best methods for near-normal insulin delivery. The development of new, robust and easily programmable insulin pumps has led to readier acceptance of this therapy by physicians and patients. In clinical trials, CSII was found to be superior to multiple daily injection regimens in many cases. Patients with unsatisfactory glucose control, frequent hypoglycaemic events, and otherwise uncontrollable morning rises of blood glucose may in particular benefit from insulin pump therapy. Glucose control can even be improved in CSII if insulin lispro is used instead of regular human insulin, as demonstrated in many clinical investigations. Possible side effects of CSII are increased risk of ketoacidosis (e.g. in the case of catheter occlusion) and side effects at the infusion site. Since the successful development of devices for continuous glucose monitoring, the development of closed-loop systems has become more and more the focus of current clinical and technological research.

Blood Glucose↗

Factors affecting longevity of homograft valves used in right ventricular outflow tract reconstruction for congenital heart disease.

BACKGROUND: Few studies have explored the long-term function of cryopreserved homograft valves used for reconstruction of the right ventricular tract (RVOT) in patients with congenital heart disease. METHODS AND RESULTS: Among 205 patients receiving cryopreserved homografts for reconstruction of the RVOT between November 1985 and April 1999, the outcome of 220 homografts in 183 operative survivors was analyzed. There were 150 pulmonary and 70 aortic homografts used. Median age at implantation was 4.4 years (mean 6.9+/-7.6 years, range 3 days to 48 years). End points included (1) patient survival, (2) homograft failure (valve explant or late death), and (3) homograft dysfunction (homograft insufficiency or homograft stenosis). Survival was 88% at 10 years. Freedom from homograft failure was 74+/-4% at 5 years and 54+/-7% at 10 years. Univariable analysis identified younger age, longer donor warm ischemic time, valve Z: value <2, and previous procedure as risk factors for homograft failure and dysfunction. Aortic homograft type and extracardiac operative technique predicted homograft failure but not dysfunction. For patients </=1 year of age, valve type did not predict failure or dysfunction. Multivariable analysis identified younger age and longer donor warm ischemic time as risk factors for homograft failure and dysfunction, whereas, Z: value <2 and aortic valve type predicted homograft valve failure. CONCLUSIONS: Homograft valves used for RVOT reconstruction provide effective intermediate palliation with excellent late survival. Factors that adversely affect graft longevity include younger age, longer donor warm ischemic time, smaller homograft size, use of aortic homograft in the older patient, and extracardiac operative technique.

Adolescent↗

Studies of the complexation of sugars by diffusion-ordered NMR spectroscopy.

In the presence of lanthanide cations, some sugars with a special relationship between their hydroxyl groups are able to form complexes in water. Diffusion-ordered NMR spectroscopy (DOSY) can be used as a tool to distinguish between the complexed and noncomplexed forms in a mixture due to the differences in their relative diffusion coefficient values. The lowest diffusion was attributed to the complexed species because of the increase in both size and molecular weight when compared with the noncomplexed forms. Mixtures of sugars of the same molecular weight and also the isomers of a single monosaccharide can be 'separated' by DOSY on the basis of their different tendencies to form complexes with different diffusion coefficient values.

Cations↗

Catalytic cysteine of thymidylate synthase is activated upon substrate binding.

The role of Ser 167 of Escherichia coli thymidylate synthase (TS) in catalysis has been characterized by kinetic and crystallographic studies. Position 167 variants including S167A, S167N, S167D, S167C, S167G, S167L, S167T, and S167V were generated by site-directed mutagenesis. Only S167A, S167G, S167T, and S167C complemented the growth of thymidine auxotrophs of E. coli in medium lacking thymidine. Steady-state kinetic analysis revealed that mutant enzymes exhibited k(cat) values 1.1-95-fold lower than that of the wild-type enzyme. Relative to wild-type TS, K(m) values of the mutant enzymes for 2'-deoxyuridylate (dUMP) were 5-90 times higher, while K(m) values for 5,10-methylenetetrahydrofolate (CH(2)H(4)folate) were 1.5-16-fold higher. The rate of dehalogenation of 5-bromo-2'-deoxyuridine 5'-monophosphate (BrdUMP), a reaction catalyzed by TS that does not require CH(2)H(4)folate as cosubstrate, by mutant TSs was analyzed and showed that only S167A and S167G catalyzed the dehalogenation reaction and values of k(cat)/K(m) for the mutant enzymes were decreased by 10- and 3000-fold, respectively. Analysis of pre-steady-state kinetics of ternary complex formation revealed that the productive binding of CH(2)H(4)folate is weaker to mutant TSs than to the wild-type enzyme. Chemical transformation constants (k(chem)) for the mutant enzymes were lower by 1.1-6.0-fold relative to the wild-type enzyme. S167A, S167T, and S167C crystallized in the I2(1)3 space group and scattered X-rays to either 1.7 A (S167A and S167T) or 2.6 A (S167C). The high-resolution data sets were refined to a R(crys) of 19.9%. In the crystals some cysteine residues were derivatized with 2-mercaptoethanol to form S,S-(2-hydroxyethyl)thiocysteine. The pattern of derivatization indicates that in the absence of bound substrate the catalytic cysteine is not more reactive than other cysteines. It is proposed that the catalytic cysteine is activated by substrate binding by a proton-transfer mechanism in which the phosphate group of the nucleotide neutralizes the charge of Arg 126', facilitating the transfer of a proton from the catalytic cysteine to a His 207-Asp 205 diad via a system of ordered water molecules.

Binding Sites↗

Electron paramagnetic resonance and spectroscopic characteristics of electrogenerated mixed-valent systems [(eta 5-C5Me5)M(mu-L)M(eta 5-C5Me5)]+ (M = Rh, Ir; L = 2,5-diiminopyrazines) in relation to the radicals [(eta 5-C5Me5)ClM(mu-L)MCl(eta 5-C5Me5)]+ and [(eta 5-C5Me5)M(mu-L)MCl(eta 5-C5Me5)]2+.

Electrochemical reduction of the dinuclear [(eta 5-C5Me5)ClM(mu-L)MCl(eta 5-C5Me5)]2+ ions (M = Rh, Ir; L = 2,5-bis(1-phenyliminoethyl)pyrazine (bpip) and 2,5-bis[1-(2,6-dimethylphenyl)iminoethyl]pyrazine (bxip)) proceeds via the paramagnetic intermediates [(eta 5-C5Me5)ClM(mu-L)MCl(eta 5-C5Me5)]+ (L = bpip) or [(eta 5-C5Me5)M(mu-L)MCl(eta 5-C5Me5)]2+ (L = bxip) and [(eta 5-C5Me5)M(mu-L)M(eta 5-C5Me5)]+. Whereas the first is clearly a radical species with a small g anisotropy, the chloride-free cations are distinguished by structured intervalence charge transfer (IVCT) bands in the near-infrared region and by rhombic electron paramagnetic resonance features between g = 1.9 and g = 2.3, which suggests considerable metal participation at the singly occupied MO. Alternatives for the d configuration assignment and for the role of the bisbidentate-conjugated bridging ligands will be discussed. The main difference between bpip and bxip systems is the destabilization of the chloride-containing forms through the bxip ligand for reasons of steric interference.

Journal Article↗

CD5-positive B cells in healthy elderly humans are a polyclonal B cell population.

B cell chronic lymphocytic leukemia (B-CLL) is a disease of the elderly and is characterized by a malignant clone of CD5+ B cells. In old mice, clonal expansions of CD5+ B cells are a common feature, and these animals frequently develop B-CLL. To investigate whether clonal expansion of CD5+ B cells also occurs in elderly humans, predisposing for the development of B-CLL, we analyzed VH gene rearrangements of CD5+ B cells from blood samples of four healthy, 65-82-years-old volunteers as markers of clonality. CD5+ and CD5-B cells were obtained by cell sorting, CDRIII of rearranged VH genes were amplified by polymerase chain reaction, and fragment length analysis was performed. All samples demonstrated a polyclonal pattern of VH gene length distribution. In addition, VH gene rearrangements were amplified and sequenced from sorted single cells of two of the donors. No clonally related CD5+ or CD5- B cells were observed. Thus, development of dominant clones of CD5+ peripheral blood B cells is unlikely to be a common trait of elderly individuals.

Aging↗

Patients at risk for low systemic oxygen delivery after the Norwood procedure.

BACKGROUND: Identification of patients at risk for inadequate systemic oxygen delivery following the Norwood procedure could allow for application of more intensive monitoring, provide for earlier intervention of decreased cardiac output, and result in improved outcome. METHODS AND RESULTS: Superior vena cava saturation (SvO2) and arteriovenous oxygen content difference were prospectively monitored as indicators of systemic oxygen delivery and recorded hourly for the first 48 hours in 29 of 33 consecutive patients following the Norwood procedure. Risk factors were evaluated using multiple linear regression to determine their impact on SvO2 and arteriovenous oxygen content difference. Age less than 8 days, weight less than 2.5 kg, aortic atresia, and prolonged cardiopulmonary bypass time were risk factors for low SvO2 and wide arteriovenous oxygen content difference (p < 0.05). Phenoxybenzamine and increasing time after operation were associated with higher SvO2 and narrower arteriovenous oxygen content difference (p < 0.05). Thirty-day survival was 97% and hospital survival was 94%. The earliest death occurred on postoperative day 20. Survival to bidirectional cavopulmonary shunt was 77%. Preoperative mechanical ventilation was the only risk factor identified for late death. CONCLUSIONS: Aortic atresia, low weight, younger age, and prolonged cardiopulmonary bypass, previously identified risk factors for mortality, were associated with decreased SvO2 and narrower arteriovenous oxygen content difference in the early postoperative period. The impact of this hemodynamic vulnerability on mortality was minimized by continuous SvO2 monitoring.

Cardiac Output, Low↗

Venous saturation and the anaerobic threshold in neonates after the Norwood procedure for hypoplastic left heart syndrome.

BACKGROUND: Reduction in oxygen delivery can lead to organ dysfunction and death by cellular hypoxia, detectable by progressive (mixed) venous oxyhemoglobin desaturation until extraction is limited at the anaerobic threshold. We sought to determine the critical level of venous oxygen saturation to maintain aerobic metabolism in neonates after the Norwood procedure (NP) for the hypoplastic left heart syndrome (HLHS). METHODS: A prospective perioperative database was maintained for demographic, hemodynamic, and laboratory data. Invasive arterial and atrial pressures, arterial saturation, oximetric superior vena cava (SVC) saturation, and end-tidal CO2 were continuously recorded and logged hourly for the first 48 postoperative hours. Arterial and venous blood gases and cooximetry were obtained at clinically appropriate intervals. SVC saturation was used as an approximation of mixed venous saturation (SvO2). A standard base excess (BE) less than -4 mEq/L (BElo), or a change exceeding -2 mEq/L/h (deltaBElo), were used as indicators of anaerobic metabolism. The relationship between SvO2 and BE was tested by analysis of variance and covariance for repeated measures; the binomial risk of BElo or deltaBElo at SvO2 strata was tested by the likelihood ratio test and logistic regression, with cutoff at p < 0.05. RESULTS: Complete data were available in 48 of 51 consecutive patients undergoing NP yielding 2,074 valid separate determinations. BE was strongly related to SvO2 (model R2 = 0.40, p < 0.0001) with minimal change after adjustment for physiologic covariates. The risk of anaerobic metabolism was 4.8% overall, but rose to 29% when SvO2 was 30% or below (p < 0.0001). Survival was 100% at 1 week and 94% at hospital discharge. CONCLUSIONS: Analysis of acid-base changes revealed an apparent anaerobic threshold when SvO2 fell below 30%. Clinical management to maintain SvO2 above this threshold yielded low mortality.

Anaerobic Threshold↗

Calpain-mediated proteolytic cleavage of troponin I induced by hypoxia or metabolic inhibition in cultured neonatal cardiomyocytes.

While ischemic damage to myofibrillar proteins is thought to be responsible in part for depressed cardiac function, the relation between myofilament protein breakdown and chronic hypoxia has not been defined. We previously characterized a chemical hypoxia model of neonatal cardiomyocytes mediated by 1 mM azide that exhibits features of calpain activation (Mol Cell Biochem 178:141-149, 1998). We here show that both hypoxia and azide-mediated metabolic inhibition induced heme oxygenase-1 expression, and caused cell death associated with lipid peroxidation. While blocking calcium influx or inhibiting calpain activity efficiently attenuated hypoxia-induced cell injury, it failed to prevent cell injury caused by adenoviral overexpression of the tumor suppressor protein p53. Inhibitors of caspases, on the other hand, suppressed cell injury caused by p53 overexpression. Hypoxia caused selective cleavage of troponin I (TnI), which could be suppressed by either nifedipine or calpeptin. Other myofilament proteins such as troponin T, myosin heavy chain, and actin appeared to remain largely intact. p53-mediated cell injury exhibited proteolysis of the caspase protein substrate lamin B without appreciable breakdown of TnI. We suggest that calpain-induced TnI breakdown may constitute a unique biochemical marker associated with chronically hypoxic cardiomyocytes.

Animals↗

Mineralocorticoid receptor knockout mice: lessons on Na+ metabolism.

The mineralocorticoid receptor (MR) binds aldosterone and glucocorticoids with equal affinity. In aldosterone target tissues, like the epithelial cells of the distal colon and the principal cells of the collecting ducts in the kidney, the MR is protected from glucocorticoids by the action of the enzyme 11beta-hydroxysteroid-dehydrogenase type 2 (11betaOHSD2), allowing aldosterone to specifically activate the receptor. However, in MR-expressing cells, which lack 11betaOHSD2, like the neurons of the limbic system in the brain, MR is mainly activated by glucocorticoids. MR knockout mice die in the second week after birth, showing at day 8 symptoms of pseudohypoaldosteronism with hyponatremia, hyperkalemia, high renal salt wasting, and a strongly activated renin-angiotensin-aldosterone system (RAAS). The activity of the amiloride-sensitive epithelial Na+ channel (ENaC) is strongly reduced in colon and kidney, but there is no down-regulation of the mRNA abundance of the three ENaC subunits. Daily subcutaneous injections of isotonic NaCl solution until weaning and continued oral NaCl supply lead to survival of the MR knockout mice. The NaCl-rescued MR knockout mice display a strongly enhanced fractional renal excretion of Na+, hyperkalemia, and a persistently strongly activated RAAS. There is almost no renal ENaC activity. The renal mRNA abundance of alphaENaC is reduced by 30%, whereas betaENaC and gammaENaC are not altered.

Animals↗

Complex long-segment intestinal dysganglionosis.

A case is reported with aganglionosis of the rectum, sigma, and descending colon; dysganglionosis with heterotopic ganglionic cells in the muscularis propria of the hypoganglionic transverse colon; and extreme hypoganglionosis (without detection of ganglionic cells) of the ascending colon and distal ileum. The ileum showed a transition zone with hypoganglionosis and intestinal neuronal dysplasia (IND) type B. As to the etiology of such complex intestinal innervation defects, pre- and perinatal perfusion deficits must be considered because their localization seems to be linked to the vascular anatomy of the colon. Early diagnosis may be difficult, causing a delay in operative treatment and multiple operations. Different manifestations of dysganglionosis may be found in the same patient. The classical continuum of distal aganglionosis followed by proximal hypo- or dysganglionosis and then normally innervated bowel may not always be present. Therefore, in children with recurrent (sub-)ileus after resection of an aganglionic bowel segment, additional dysganglionosis such as IND or hypoganglionosis or even complex intestinal dysganglionosis should be excluded by full-thickness colon and small bowel biopsies.

Hirschsprung Disease↗

[Low-field MRI of the ankle joint: initial experience in children and adolescents using an open 0.2 T MR-system].

PURPOSE: To evaluate the feasibility and diagnostic confidence of MRI with an open low field System (Magnetom open, Siemens, Germany) in children with predominantly traumatic disorders. MATERIAL AND METHODS: Conventional X-rays and MRI examinations have been evaluated in 55 children. MRI was performed at an open 0.2 T MR-unit. The study protocol comprised coronal STIR-sequence, an angulated T2 weighted TSE-sequence and T1 weighted SE-sequence. RESULTS: MRI showed ligamental rupture in 33/50 (60%) cases. Injuries of the ATFL were most frequent (27/33); osseous ligamental tears occurred in approx. 50% of all cases. Fractures of the distal tibia and fibula were diagnosed in 28/55 children. 15/28 cases showed an involvement of the epiphysis. We found occult fractures in 11/28 children. Fractures, diagnosed by conventional x-rays, were excluded in 6 cases. Therapy changed in 35/55 patients on the basis of MRI-findings. CONCLUSION: Low-field MRI of the ankle joint in children and adolescents is able to show numerous pathological conditions. We recommend low-field MRI of the ankle in children with persistent or unclear pain of the ankle joint and inconspicuous conventional x-ray.

Adolescent↗