Protein kinase B (PKB) is a member of the second messenger subfamily of protein kinases. The three isoforms of PKB identified have an amino-terminal pleckstrin homology domain, a central kinase domain, and a carboxy-terminal regulatory domain. PKB is the major downstream target of receptor tyrosine kinases that signal via the phosphoinositide (PI) 3-kinase. The crucial role of lipid second messengers in PKB activation has been dissected through the use of the PI 3-kinase-specific inhibitors wortmannin and LY294002. Receptor-activated PI 3-kinase synthesises the lipid second messenger PI-3,4,5-trisphosphate, leading to the recruitment of PKB to the membrane. Membrane attachment of PKB is mediated by its pleckstrin homology domain binding to PI-3,4,5-trisphosphate or PI-3,4-bisphosphate with high affinity. Activation of PKB alpha and beta is then achieved at the plasma membrane by phosphorylation of Thr308/309 in the A-loop of the kinase domain and Ser473/474 in the carboxy-terminal regulatory region, respectively. The upstream kinase that phosphorylates PKB on Thr308, termed PI-dependent protein kinase-1, has been identified and extensively characterised. A candidate for the Ser473/474 kinase, termed the integrin-linked kinase, has been identified recently. Activated PKB is implicated in glucose metabolism, transcriptional control, and in the regulation of apoptosis in many different cell types. Stimulation of PKB activity protects cells from apoptosis by phosphorylation and inactivation of the pro-apoptotic protein BAD. These results could explain why PKB is overexpressed in some ovarian, breast, and pancreatic carcinomas.

Animals↗

PubMedDate not supplied

[Surgical correction of malunited fractures of the forearm in children].

AIM: In our goal-oriented society the demands for a forearm with full function are increasing. Functional deficits are not acceptable even if they persist only for a limited period of time. Therefore a rising number of surgical corrections of malunited forearm fractures in the pediatric patient has been performed during the last years. However literature about indication, technique and outcome in these patients is rare. For that reason we report our experience about surgical correction of malunited fractures of the forearm in 14 children. METHODS: Fourteen patients with an average age of 13 years at the time of surgical correction of a malunited fracture of the forearm were included. Seven had a deformity of the shaft, five at the distal forearm without and two with growth disturbance. Malunions without growth disturbance were corrected with an osteotomy and plate fixation. Those with growth disturbance were first treated with callus distraction. Previous to and 24 (3 to 100) months after surgical correction the patients were examined clinically and radiologically. Range of motion was noted. Additionally to the range of motion, grip strength and pain (VAS) were documented. Patients with correction of the distal forearm were asked to fill out the DASH questionnaire. RESULTS: In all groups a significant increase of the range of motion was noted in pro-/supination of 61 per cent to 85-0-80 degrees. In patients with distal correction additionally the range of motion in extension/flexion of the wrist improved 30 per cent to 70-0-65 degrees and in ulnar/radialduction 22 per cent to 30-0-35 degrees. At follow-up the grip strength following distal corrections was 98 per cent of the opposite side. The patients had no pain (VAS < 3 points). The median subjective functional result was excellent with a median DASH score of 3.5 points. CONCLUSIONS: Our results show that potent techniques for surgical correction of malunited forearm fractures in the growing skeleton are available. These techniques allow excellent functional outcome.

Adolescent↗

PubMedDate not supplied

Effect of a liquid diet with and without soluble fiber supplementation on intestinal transit and cholecystokinin release in volunteers.

The effect of adding fiber to liquid formula diets on gastrointestinal transit is still controversial. Different fiber types (soluble vs insoluble) and different methodology of transit time measurements yielded variable results. Factors affecting transit include colonic fermentation, neural, and hormonal factors. We have therefore compared the effects of a standardized normal diet and two liquid formula diets with and without supplementation of a soluble fiber (21 g/L) on orocecal transit time measured by the hydrogen lactulose breath test, colonic transit time measured by radiopaque markers with an abdominal x-ray, bowel movements, stool consistency, and cholecystokinin release in 12 healthy male volunteers. The diets were consumed in a randomized order, each one for 7 days. The addition of soluble fiber did not affect orocecal transit time. Colonic transit time, however, was significantly prolonged (55 h) with fiber supplementation compared with the liquid diet (39 h) and the self-selected diet (30 h) (p < .01). Stool frequency and consistency was not significantly affected. During administration of both liquid diets, fasting cholecystokinin concentrations were significantly elevated compared with the concentrations found with a self-selected diet (p < .05). The fasting cholecystokinin concentration correlated significantly with the increase of segmental (right colon) colonic transit time (p = .02). The prolongation of colonic transit time in liquid diet-fed volunteers might be caused by the combined effect of increased colonic fermentation and high basal cholecystokinin concentrations.

Adult↗

PubMedDate not supplied

Regulation of protein kinase B.

Protein kinase B (PKB) is a member of the second-messenger regulated subfamily of protein kinases implicated in signalling downstream of growth factor and insulin receptor tyrosine kinases and phosphatidylinositol 3-kinase (PI 3-kinase). PKB is activated by phosphorylation in response to mitogens and survival factors. Membrane recruitment driven by lipid second-messengers derived from PI 3-kinase leads to PKB phosphorylation and activation by upstream kinases (PDK1 and an as yet identified protein kinase). Prolonged stimulation with growth factors results in nuclear translocation, providing evidence that PKB activation at the plasma membrane precedes its nuclear translocation and supporting a role for PKB in signalling from receptor tyrosine kinases to the nucleus.

Animals↗

PubMedDate not supplied

[Speech and intelligence performance in relation to social class and family status].

Explore the source record for details and available documents.

Adolescent↗

PubMedDate not supplied

[Qualification of elderly workers in industry--problems and opportunities].

The aim of the research project was to find out the conditions of a successful occupational qualification of older workers in the Federal Republic of Germany. The more recent results of psychological research concerning the learning capacities of older people suppose that older workers can also be qualified successfully with regard to the requirements of their job. However, the project results reveal that certain basic conditions should be fulfilled for the qualification of older workers. Training measures should take place during work time; the fact has to be respected that older workers need more time to learn than younger workers; the learning material should be divided into short, separated units; older workers should not be obliged to do home-work; the creation of learning groups among the older workers should refer to different degrees of qualification, not to the age of the workers.

Aged↗

PubMedDate not supplied

[A foldable cardboard box for drying and storage of by cotton swab collected biological samples].

The ability to perform successful DNA analysis on biological evidence obtained at a crime scene or during a sexual assault examination depends very much on the first step--how specimens are collected and preserved. Body fluids and their wet or dry stains, are often recovered using dry cotton swabs or cotton swabs moistened with sterile water or saline. In order to prevent decomposition and deterioration of a specimen, resulting in degradation or loss of DNA, it is recommended to either air dry or freeze these swabs as soon as possible after collection. We designed a simple, foldable cardboard box, which is suitable for the drying and storage of biological evidence collected on cotton swabs. Immediately after collection swabs are placed into the drying racks within the cardboard box, which is subsequently folded, labeled, sealed and initialed. At room temperature swabs completely air dry within the sealed box within 6-9 hours. In this box the evidence is properly packed, labelled and sealed, thus preventing cross contamination, degradation and sample switch. It is a valuable device for the collection of biological evidence at a crime scene, during sexual assault examinations, and for the collection of buccal swabs for PCR-based databasing and paternity testing.

DNA↗