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Background:LGR5 is an important marker of intestinal stem cells and performs its vital functions at the cell membrane. Despite the importance of LGR5 to both normal and cancer stem cell biology, it is not known how microenvironmental stress affects the expression and subcellular distribution of the protein.Methods:Nutrient stress was induced through glucose starvation. Glycosylation status was assessed using endoglycosidase or tunicamycin treatment. Flow cytometry and confocal microscopy were used to assess subcellular distribution of LGR5.Results:Glucose deprivation altered the glycosylation status of LGR5 resulting in reduced protein stability and cell surface expression. Furthermore, inhibiting LGR5 glycosylation resulted in depleted surface expression and reduced localisation in the cis-Golgi network.Conclusions:Nutrient stress within a tumour microenvironment has the capacity to alter LGR5 protein stability and membrane localisation through modulation of LGR5 glycosylation status. As LGR5 surface localisation is required for enhanced Wnt signalling, this is the first report to show a mechanism by which the microenvironment could affect LGR5 function. [ABSTRACT FROM AUTHOR]

A variety of carcinogenic heterocyclic amines are produced during the cooking of meat at high temperatures. These carcinogens are metabolized by N-acetyltransferases (NAT), which are polymorphic in the population. This study examined associations between prostate cancer (PCa) and the consumption of different kinds of meat, heterocyclic amine intake and NAT genotypes. PCa patients and controls were recruited in the Syracuse, NY area. Levels of meat and heterocyclic amine intakes were determined from validated surveys and NAT genotypes were determined by the sequences of PCR-amplified DNA from buccal swabs. A total of 152 cases and 161 controls were eligible for analysis. There was an association between PCa and history of PCa in the first-degree blood relatives (OR=4.59, 95%CI 2.21-9.70), and family history of bladder cancer (P<0.02). However, there was no association with the history of other cancers. There was no association between PCa and either 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) intake, or NAT1 and NAT2 genotypes. However, there was a trend of association with MeIQx and with rapid NAT2 and NAT1*10 in combination with PhIP. A new NAT1 allele with a frequency of one out of 544 chromosomes was found in the Caucasian subjects.Prostate Cancer and Prostatic Diseases (2005) 8, 69-74. doi:10.1038/sj.pcan.4500780 Published online 1 February 2005 [ABSTRACT FROM AUTHOR]

Based on data from the Annual Medical School Questionnaire of the Liaison Committee on Medical Education (LCME), to which 100% of schools responded, we found that revenue supporting programs and activities of the 125 accredited medical schools in the United States totaled $36997 million in 1997-1998. A large proportion of revenue (79%) was derived from 3 sources: practice plans ($12559 million; 33.9%), grants and contracts ($10916 million; 29.5%), and hospital support ($5741 million; 15.5%). An analysis of revenue trends revealed that medical schools, in aggregate, have continued to experience growth during the last 2 years. However, the aggregate numbers mask considerable variation among schools with regard to changes in financing. Between 1995-1996 and 1996-1997, 46 schools (37%) reported constant-dollar declines in the sum of practice plan and hospital revenue, and 50 schools (40%) reported a decline from 1996-1997 to 1997-1998. The financial data reviewed in this report demonstrate the continued dependence of medical schools on faculty-generated sources of revenue and confirm the perception that a growing number of medical schools are experiencing reductions in key sources of financial support. Current and projected reductions in teaching hospital revenue due to the implementation of the Balanced Budget Amendment are expected to erode further hospital support for medical school programs and activities. [ABSTRACT FROM AUTHOR]

Western Europe became intensely urbanized under the Roman Empire. It is argued that the dynamic for that urbanization came from changes in cultural expression among the provincial ruling classes, providing services and amenities as expressions of social competition, which survive in archaeological form particularly in the civic public buildings. Political control of the towns remained in the hands of that traditional ruling class; no distinctly urban economic group emerged with significant power. The decline in interest in the urban public buildings during the Late Roman Empire demonstrated in excavation in much of Europe therefore shows changes in social attitudes among the provincial ruling classes, rather than the end of urbanism. The economic cycle was more complex and dependent on the widest issues of the fall of the Roman Empire. [ABSTRACT FROM PUBLISHER]

Based on data from the Annual Medical School Questionnaire of the Liaison Committee on Medical Education, to which 100% of schools responded, the revenues that supported the programs and activities of the 125 accredited medical schools in the United States totaled $34897 million in 1996-1997. A large proportion (78.9%) of these revenues was derived from 3 sources: practice plans, grants and contracts, and hospital support. Both public and private medical schools, in aggregate, have continued to experience growth throughout the last decade but at a progressively slower rate, primarily because of a slowing in the growth of practice plan revenues. Federal revenues supporting research in public and private medical schools since 1992-1993 have grown at annualized, constant-dollar rates of 5.6% and 4%, respectively. Growth in state and local appropriations to public medical schools has tended to lag behind inflation. Growth in reported revenues from endowments that are used to support programs at private medical schools is on the rise. The aggregate numbers mask considerable variation among schools with regard to changes in financing. A small, but appreciable, number of schools have witnessed a constant-dollar decline in their total practice plan revenues since 1992-1993. The financial data reviewed in this report demonstrate the continued dependence of medical schools on faculty-generated sources of revenue and confirm the perception that medical schools, as a group, are experiencing constraints on the growth of their enterprises. [ABSTRACT FROM AUTHOR]

SUMMARY 53 paediatric patients underwent Metrizamide myelography with pre- and post-operative assessment as per the protocol previously outlined. Despite its recognised minimal neurotoxicity, no convulsions or depression of vital signs were recorded. Adverse reactions were within acceptable clinical levels. The diagnostic accuracy was felt to be superior to oily contrast media. The ease of examination, with the increased diagnostic yield and the safety of its use anywhere in the subarachnoid space, makes Metrizamide particularly suitable for myelography in children. [ABSTRACT FROM AUTHOR]

- It is unnecessary to treat laboratory-diagnosed urinary tract infection in the absence of clinical symptoms and signs in patients from whom specimens of urine have been taken from indwelling urethral catheters left in situ for more than one week. If there is clinical evidence of infection, the catheter should be removed, a new catheter inserted and a specimen taken for examination. Alternatively, a suprapubic aspirate of urine may be examined bacteriologically as a treatment guide. In the absence of symptoms or other signs of infection it is doubtful whether chemotherapy is indicated. [ABSTRACT FROM AUTHOR]

The efficacy of a selective fusimotor suppressant, the phenothiazine (+/-)-10-3-dimethylamino-2-methylpropyl)-2-valeroylphenothiazine, has been assessed in a double-blind crossover trail in eight patients suffering from cerebral spasticity and one patient suffering from spinal spasticity. Dosage was 40 mg daily. Independent clinical and electromyographic methods of assessment were used. The active agent produced a small but significant reduction in spasticity, although this was of clinical value in only a few patients. There were few side-effects. It is recommended that further studies using higher dosages be undertaken. [ABSTRACT FROM AUTHOR]

N-acylation of aryl N-methylcarbamates is known to reduce their mammalian toxicity considerably without adversely affecting their insecticidal activity. It has now been found that N-acylation of several insecticidal oxime carbamates results in loss of toxicity both to insects and mammals. Kinetic data for base-catalysed solvolysis and inhibition of acetylcholinesterase, together with published work on metabolism, are combined to provide a rationale for this unexpected observation and to account for the selective toxicity of aryl N-acetyl- N-methylcarbamates. [ABSTRACT FROM AUTHOR]

The efficacy of cyclobenzaprine 60 mg/day in the treatment of spasticity was assessed in a double-blind crossover trial of two weeks' duration in 15 patients suffering from cerebral or spinal spasticity. Independent clinical and electromyographic methods were used. The effects of cyclobenzaprine did not differ significantly from those of placebo. The administration of a higher dosage, 150 mg/day, to one patient revealed a dose-related response, but the degree of improvement was clinically small. Apart from a skin rash there were no significant untoward effects of therapy. [ABSTRACT FROM AUTHOR]

In a preliminary controlled trial, CIBA 34,647-Ba, a gamma aminobutyric acid derivative, was found to be more effective than placebo in reducing spasticity due to spinal injuries. In an uncontrolled trial, 34,647-Ba also appeared more effective than diazepam. The intensity of spasticity was measured electromyographically by the amplitude of the stretch reflex at various velocities, and the results were correlated with those obtained by clinical assessment. 34,647-Ba was effective in both complete and incomplete spinal cord lesions and it is suggested that it has an action at the spinal level. No significant side-effects were encountered. [ABSTRACT FROM AUTHOR]

Based on data from the Annual Medical School Questionnaire of the Liaison Committee on Medical Education, to which 100% of the 125 accredited allopathic US medical schools responded, we found that revenue supporting programs and activities of the 125 accredited medical schools in the United States totaled $39,761 million in 1998-1999. Three sources accounted for 79.3% of total revenues: practice plans ($13,724 million; 34.5%), grants and contracts ($11, 982 million; 30.1%), and hospital support ($5814 million; 14.6%). In the aggregate, total revenues increased by 7.4% between 1997-1998 and 1998-1999, a consequence at least in part due to a 2.9% increase in the number of full-time faculty. The largest increase in dollar amount came from grants and contracts ($1101 million; 10.2% increase). Revenue increases were not evenly distributed across the schools. Increases of 10% or more in key revenue sources-practice plans and hospital support-were reported by approximately one fourth of all schools. Another one fourth reported decreases in these same sources. JAMA. 2000;284:1127-1129 [ABSTRACT FROM AUTHOR]