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Patterns of mRNA expression during early cell growth differ in kidney epithelial cells destined to undergo compensatory hypertrophy versus regenerative hyperplasia.

An increase in cell size and protein content is characteristic of cells undergoing hypertrophy and of replicating cells prior to DNA synthesis. Cell enlargement in the two situations could be regulated by similar early events with an interruption of the cell cycle occurring in hypertrophy, or the two processes could be uncoupled. In vivo models were used to compare hypertrophy induced by unilateral nephrectomy and hyperplasia induced by folic acid injection in rabbit renal cortical cells. Within 48 hr, cell volume increased in both groups but the number of cells in the cell cycle and DNA synthesis was increased only after folic acid. Patterns of mRNA expression of the following three groups of cell cycle-dependent genes were analyzed: (i) protooncogenes (c-fos, c-myc, and c-Ha-ras), (ii) structural protein genes (vimentin and beta-actin), and (iii) transport protein genes (Na+, K+-ATPase, ADP-ATP translocase, and calcyclin). mRNAs for all genes, except calcyclin and c-Ha-ras, were detected in controls. Folic acid generally induced rapid, transient increases in mRNA levels, but after unilateral nephrectomy, expression of most mRNAs showed a gradual, progressive increase. These data indicate that gene expression in the early stages of cell enlargement differs in cells destined to undergo proliferation vs. hypertrophy. The term "sustained message amplification" is proposed to describe the hypertrophied cell.

Animals↗

Generation of a fusion partner to sample the repertoire of splenic B cells destined for apoptosis.

B cells proliferate and diversify in germinal centers in response to antigen. Only a small percentage of these B cells will emerge to form the serum antibody response. Other B cells making lower affinity antibodies, acquiring nonsense mutations, or expressing autoreactivity as a result of somatic mutation undergo an apoptotic cell death and are not efficiently sampled in current analyses of B-cell hybridomas. We have demonstrated that expression of bcl-2 in the NSO myeloma fusion partner leads to a higher yield of viable hybridomas, with a selective increase in hybridomas from B cells that produce autoantibodies and are seldom recovered when spleen cells from non-autoimmune mice are fused to the conventional NSO cell line. Using this fusion partner, we have generated hybridomas from anti-DNA antibody-producing transgenic B cells that are anergic in vivo and destined for apoptosis. These studies provide a strategy to sample the repertoire of B cells that arise in vivo but are not selected to contribute to the expressed antibody response. Furthermore, they demonstrate that restricted expression of bcl-2 in B cells contributes to the maintenance of self-tolerance in secondary lymphoid organs.

Animals↗

Investigating discharge destinations for schizophrenic patients.

An audit of hospital records of 542 patients diagnosed as having schizophrenia discharged in the years 1986-88 from the Princess Alexandra Hospital, Brisbane, showed that 46% of patients left hospital to live with other family members, usually parents or spouses. Analysis of destination suggested that the extent of patient-family connectedness increases when the patient is younger, has had fewer admissions, or has had the illness for a shorter period of time.

Activities of Daily Living↗

Rehabilitation outcomes for brain injured patients in Australia: functional status, length of stay and discharge destination.

This study describes the rehabilitation length of stay (LOS), discharge destination and discharge functional status of 149 patients admitted with traumatic brain injury (TBI) to an Australian hospital over a 5-year period. Hospital charts of patients admitted between 1993-1998 were reviewed. Average LOS over the 5-year time period was 61.8 days and only decreased nominally over this time. Longer LOS was predicted by lower admission motor FIM scores and presence of comorbidities. Mean admission and discharge motor FIM scores were 58 and 79, which represented a gain of 21 points. Higher discharge motor FIM scores were predicted by higher admission motor FIM scores and younger age. FIM gain was predicted by cognitive status and age. Most patients, 88%, were discharged back to the community, with 30% changing their living setting or situation. Changing living status was predicted by living alone and having poorer functional status on admission.

Activities of Daily Living↗

College students' binge drinking at a beach-front destination during spring break.

Four hundred forty-two women and 341 men were surveyed at Panama City Beach, Florida, to assess the effects of gender, age, fraternity or sorority membership, and travel motivation on alcohol consumption and binge drinking during spring break. The mean number of drinks consumed the previous day was 18 for men and 10 for women; 91.7% of the men and 78.1% of the women had participated in a binge-drinking episode during the previous day. Respondents less than 21 years old consumed less alcohol and reported significantly lower frequencies of intoxication than those over 21. The men's reported levels of alcohol consumption, binge drinking, and intoxication to the point of sickness were significantly higher than the women's, but fraternity or sorority membership was not associated with higher levels of consumption. Students motivated to visit the specific destination because of its "party" reputation consumed significantly more alcohol than students who cited other reasons for going there.

Adult↗

Passage of serum-destined proteins through the Golgi apparatus of rat liver. An examination of heavy and light Golgi fractions.

The participation of hepatic Golgi apparatus in the intracellular transport of blood-destined proteins has been analyzed using Golgi fractions enriched in cis and trans components of the Golgi apparatus. SDS-polyacrylamide gel electrophoresis of the liver Golgi fractions showed several proteins corresponding in relative proportions and mobilities with serum proteins. After a pulse injection of labeled leucine, the secretory content of the cis Golgi fraction was labeled earlier than the trans Golgi fraction. Taken together, the results show the participation of the liver Golgi apparatus in the secretion of most of the serum proteins and provide documentation for a sequential progression of secretory protein through the cis and trans components of the Golgi apparatus.

Animals↗

Evidence that all newly synthesized proteins destined for fast axonal transport pass through the Golgi apparatus.

Effects of the sodium ionophore, monensin, were examined on the passage from neuronal cell body to axon of materials undergoing fast intracellular transport. In vitro exposure of bullfrog dorsal root ganglia to concentrations of drug less than 1.0 micron led to a dose-dependent depression in the amount of fast-transported [3H]leucine- or [3H]glycerol-labeled material appearing in the nerve trunk. Incorporation of either precursor was unaffected. Exposure of a desheathed nerve trunk to similar concentrations of monensin, while ganglia were incubated in drug-free medium, had no effect on transport. With [3H]fucose as precursor, fast transport of labeled glycoproteins was depressed to the same extent as with [3H]leucine; synthesis, again, was unaffected. By contrast, with [3H]galactose as precursor, an apparent reduction in transport of labeled glycoproteins was accounted for by a marked depression in incorporation. The inference from these findings, that monensin acts to block fast transport at the level of the Golgi apparatus, was supported by ultrastructural examination of the drug-treated neurons. An extensive and selective disruption of Golgi saccules was observed, accompanied by an accumulation of clumped smooth membranous cisternae. Quantitative analyses of 48 individual fast-transported protein species, after separation by two-dimensional gel electrophoresis, revealed that monensin depresses all proteins to a similar extent. These results indicate that passage through the Golgi apparatus is an obligatory step in the intracellular routing of materials destined for fast axonal transport.

Animals↗

Preferential origin and layer destination of GAD65-GFP cortical interneurons.

To identify the origin and track the migratory pathway of specific subpopulations of GABAergic interneurons, we studied tangential migration in a recently developed GAD65-GFP transgenic mouse strain. First, we used immunohistochemical methods to characterize the expression of specific neurochemical markers in the GAD65-GFP neurons. Then, organotypic cultures were used in combination with birth-dating studies to determine the time of generation, place of origin and migratory route of these cells. From E14 to E15, the highest density of GAD65-GFP cells was seen in the lower intermediate zone; however, at later stages more GAD65-GFP cells were observed in the subventricular zone. Migratory GAD65-GFP cells express GAD65, but not calretinin or reelin. Surprisingly, only 4% were calbindin immunopositive. At P21, GAD65-GFP cells were found predominantly in layers II-III and expressed calretinin and neuropeptide Y. Remarkably, almost all cholecystokinin-positive but very few parvalbumin-positive neurons expressed GFP. In vitro studies demonstrated that the caudal ganglionic eminence gives rise to a large proportion of GAD65-GFP interneurons and in vivo birth-dating experiments showed that GAD65-GFP interneurons in supragranular layers are born at late embryonic development. Taken together these results support the idea that the destination layer of GABAergic interneurons is closely linked to their place of origin and time of generation.

Animals↗

In vitro prostaglandin production by bovine corpora lutea destined to be normal or short-lived.

Basal and calcium ionophore (CaI)-influenced production of prostaglandins (PGs) by corpora lutea (CL) destined to be normal or short-lived were compared. Ovulation was induced in 24 lactating beef cows with human chorionic gonadotropin (hCG, 1000 IU) administered between 35 and 40 days postpartum. Ten cows received norgestomet implants for 9 days prior to induced ovulation (Normal CL) and 14 served as untreated controls (Subnormal CL). Five cows in each treatment were unilaterally ovariectomized on Day 6 (Day 0 = day of hCG administration) and CL were collected. Blood samples were collected daily through-out the experimental period from cows not ovariectomized. Plasma progesterone (P4) in ovary-intact animals indicated that short-lived CL were induced in 8/8 cows not pretreated with norgestomet, and normal luteal lifespan was observed in 4/5 implanted cows. Dispersed luteal cells were incubated for 8 h with 0, 0.05, 0.5, or 5 microM CaI (A23187). Incubation media were analyzed for P4, PGF2 alpha, 6-keto-PGF1 alpha (PGI), and PGE2. The weight, cell number, and basal or CaI-influenced production of P4 did not differ between Normal CL and Subnormal CL. Basal production of PGF2 alpha, PGI, and PGE2 was higher in Subnormal CL than in Normal CL (p less than 0.05). In response to 0.05 microM CaI, PGF2 alpha was stimulated in Subnormal CL (p less than 0.01), while PGI (p less than 0.05) and PGE2 (p less than 0.1) were increased in Normal CL. Production of PGs was reduced by 5 microM CaI in Subnormal CL (p less than 0.01), but not in Normal CL.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Sunbathing intentions in Irish people travelling to Mediterranean summer holiday destinations.

As exposure to UV light is thought to be the most significant environmental and behavioural risk factor for avoiding skin cancer, we have analysed the sunbathing intentions and attitudes of Irish people travelling to Mediterranean and Iberian holiday destinations. Ninety per cent of respondents planned to get a suntan on their vacation with 44% likely to burn their skin in the process. Although all intended to apply sun cream on holiday only 40% would apply >SPF 15. Sixty-four per cent planned to sunbathe between 11.00 am and 3.00 pm, with 25% intending to spend <5 hours in the sun. One-third of those intending to sunbathe for >6 hours per day were aged between 16 and 24 years. Approximately eight out of 10 people thought suntans made them feel healthier or attractive. Fifty-six per cent regularly checked their moles but men were less likely to check their skin for pigment changes. The results provide baseline information on sunbathing attitudes of Irish people. They show that while most people feel they adopt a careful approach to sunbathing, the experiences and intentions, especially in younger people, are influenced by the desirability of a suntan, and reflect a behaviour that increases their risk of skin cancer.

Adolescent↗

Left ventricular assist devices as destination therapy.

Although an estimated 16,500 Americans annually could benefit from a heart transplant, in 1999 only 2184 heart transplants were performed in the United States. These statistics emphasize the severity of the shortage of available hearts for transplantation. Circulatory support provided by an implantable Left Ventricular Assist Device (LVAD) that meets Food and Drug Administration approval as destination therapy is a promising alternative that impacts patient survival. As medical technology creates smaller implantable battery-powered circulatory assist devices that allow patients to safely live independently in the community, nursing's role must change in response. Long-term LVAD patients require strategic, anticipatory planning for extended care and emergency preparedness for mechanical support. Therefore, practitioners must familiarize themselves with these devices as they care for larger numbers of patients with implanted LVADs who require assessment and treatment of noncardiac problems during their lengthened lifespan.

Heart-Assist Devices↗

Uncertain destination dynamics.

Certain dynamical systems exhibit a sensitivity to initial conditions in which the asymptotic state is selected from an infinite number of possible states. The phase space of such systems is foliated with "attractors," each of which is associated with a particular set of initial conditions. The associated uncertain destination dynamics can be analyzed by an appropriate reduction of the full system to a subsystem that explicitly yields the dynamics.

Journal Article↗

Steering an eigenstate to a destination

The control of time evolution of a quantum state under various physical constraints is investigated and solved in the context of a two-level system. We have discovered a general scheme of steering an eigenenergy state to a destination without net nonadiabatic transitions, and we discuss how the result may be tested and utilized in practice.

Journal Article↗

Nursing education and implications for left ventricular assist device destination therapy.

The HeartMate VE Left Ventricular Assist Device (vented electric abdominally positioned pulsatile blood pump; Thoratec Corp., Pleasanton, CA), approved as a permanent support, or destination therapy, by the US Food and Drug Administration in 2002 and Medicare in 2003, is now a potential therapy for numerous patients. Postimplantation nursing care is crucial to the success of left ventricular support device therapy and long-term recipient outcome. Nurses also contribute to cost containment, making this a viable treatment for the facility and the patient. Consequently, nurses must be educated about left ventricular assist device concepts and challenges, the benefits of device placement, intensive care unit and postintensive care unit daily care requirements, and outpatient preparation. This knowledge will enable nurses to provide necessary care and to educate recipients, families, and community health care providers on how to give appropriate posthospital care.

Certification↗

Saccharomyces cerevisiae mating pheromones specifically inhibit the synthesis of proteins destined to be N-glycosylated.

alpha Factor specifically inhibits the synthesis of N-glycosylated proteins in Saccharomyces cerevisiae mating type a cells but not in alpha cells or in a/alpha diploids. a Factor has the same effect of alpha cells. The synthesis of O-glycosylated proteins is not inhibited. Although the mating pheromones act like a 'physiological tunicamycin', the mechanism of inhibition is different: not the glycosylation of proteins as such but rather the synthesis of those proteins destined to be N-glycosylated is inhibited. Thus none of a number of glycosylating enzymes tested in vitro is reduced in activity in alpha-factor-treated cells. The synthesis of the glycoprotein carboxypeptidase Y, on the other hand, is strongly inhibited by tunicamycin as well as by alpha factor; but only in the former case did carbohydrate-free protein accumulate in the cells. alpha Factor causes maximal inhibition of glycoprotein formation after as little as 30 min, long before all cells in the population are arrested in G1; moreover, release from this inhibition precedes the increase in budding index (resumption of cell division). It is postulated, therefore, that N-glycosylated proteins are required for the G1/S-phase transition in the yeast cell cycle. This is supported by previous reports that first cycle arrest in G1 occurs when (a) tunicamycin is added to growing cultures, and (b) a temperature-sensitive N-glycosylation mutant is shifted to its restrictive temperature.

Animals↗

Rural emergency medical services: patients, destinations, times, and services.

This study sought to describe the volume of use, mix of patients, origin and destination of runs, times and distances to care, and the volume of clinical services provided in a rural emergency medical services region. This study summarizes all 6,080 rural emergency ambulance trip reports filed from April through September 1991 from the 12 rural counties surrounding Augusta, GA. Rural ambulances are regularly used and are used extensively by elderly populations. The pattern of services provided suggests that while advanced care may or may not have been indicated, it was rarely provided and that rural emergency medical service programs should consider a greater reliance on basic life support teams.

Adolescent↗

Effect of mass medication with antibiotics at feedlot entry on the health and growth rate of cattle destined for the Australian domestic market.

OBJECTIVE: To examine the effectiveness of mass medication with long acting antibiotics at feedlot entry on lot-fed Australian domestic cattle during a period of high risk for bovine respiratory disease (BRD). DESIGN: Systematic allocation at feedlot entry of tilmicosin, long acting oxytetracycline or no antibiotic treatment, to cattle lot fed for the Australian domestic market. Comparisons of growth rate, disease occurrence and mortality were made between the groups at the conclusion of the feeding period. RESULTS: Cattle medicated with tilmicosin at 10 mg/kg body weight on entry to the feedlot grew 0.08 kg/d faster than cattle medicated with oxytetracycline at 20 mg/kg body weight and non-medicated cattle. There was no significant difference in growth rate between oxytetracycline medicated cattle and cattle not medicated with antibiotic at feedlot entry. Cattle medicated with tilmicosin at feedlot entry had 8 fewer cases of disease per 100 animals compared with cattle not medicated with antibiotic at feedlot entry. There was no significant difference in disease occurrence between oxytetracycline medicated cattle and those not medicated with antibiotic at feedlot entry. CONCLUSION: Mass medication with tilmicosin at feedlot entry of cattle destined for the Australian domestic market may be used to reduce disease occurrence and increase growth rate during periods of high risk for BRD.

Animals↗

Effects of vagotomy, atropine, hexamethonium and adrenaline on the destination in the stomach of liquids sucked by milk-fed lambs and calves.

1. The normal passage to the abomasum of liquid sucked by lambs and calves was confirmed in radiographic studies to be changed to passage of liquid to the reticulum and rumen after cervical or abdominal vagotomy.2. The effects of hexamethonium (8-10 mg kg(-1) I.V.) were similar to those of vagotomy.3. Atropine (200-800 mug kg(-1) I.V.) had either no detectable effect on the destination in the stomach of liquid sucked by lambs or caused a partial failure of the reticular groove mechanism.4. Fluid sucked by lambs passed wholly to the abomasum after adrenaline (5-40 mug kg(-1) I.V.).5. Atropine and adrenaline caused a greater dysfunction of the reticular groove mechanisms in calves than in lambs.6. Contraction of the reticular groove was observed via rumen fistulae in three lambs. Eversion of the caudal oesophagus into the reticulum which occurred when saliva was swallowed into the reticulum and rumen was not observed when liquids were sucked from a bottle.7. The continued passage to the abomasum of sucked liquid in atropinized lambs has been taken as an indication of the importance of caudal oesophageal reactions, tonic activity of the reticular groove and the atropine-resistant vagally induced opening of the reticulo-omasal orifice in the reticular groove mechanism.

Abomasum↗