Sialyltransferase activity and hepatic tumor growth in a nude mouse model of colorectal cancer metastases.

Sialyltransferase activity (EC 2.4.99.6) was measured in the microsomal fraction of colorectal cancer cell lines using an assay based on the incorporation of [14C]CMP-sialic acid into asialofetuin. In the poorly differentiated lines MIP101 and Clone A, sialyltransferase activity had a Vmax of 0.36 and 0.31 nmol/mg protein/h, respectively, while the moderately differentiated to well-differentiated cell lines HT-29, CCL188, and CX-1 had Vmaxs of 2.46, 1.05, and 1.24 nmol/mg protein/h, respectively. All cell lines tested had a Km of 15.4 (+/- 0.7)(SD) mumol/liter. The better differentiated cells had higher levels of sialyltransferase activity, which correlated with their higher levels of sialic acid and their enhanced ability to form liver metastases in the nude mouse following intrasplenic injection compared to the poorly differentiated cell lines. Treatment of the cell lines with KI-8110, a CMP-sialic acid derivative which prevents incorporation of sialic acid into glycoconjugates, resulted in reduced formation of hepatic metastases by the colorectal carcinoma cell lines in the nude mouse model. It is suggested that reduced sialylation of adhesion molecules such as carcinoembryonic antigen may change the biology of the tumor cell, one consequence of which is the prevention of implantation of the cells into distant sites, resulting in a reduced incidence of metastases.     

Pharmacokinetics of moxonidine after single and repeated daily doses in healthy volunteers

The pharmacokinetics of the centrally acting alpha-2 agonist moxonidine were investigated in 12 healthy male subjects after single and repeated oral doses (q12h for five days) of moxonidine 0.2 mg. Plasma concentration-time data followed the general characteristics of a one-compartment model with first-order absorption. Peak plasma concentrations of 1.29 +/- 0.32 ng/mL were achieved 0.74 +/- 0.35 hours after ingestion of a 0.2-mg tablet. The terminal half-life of elimination was 2.12 +/- 0.58 hours. The oral clearance (CL/F) amounted to 830 +/- 171 mL/min with renal elimination being the major route of elimination. No significant differences in pharmacokinetic parameters could be observed following repeated dosing over five days.     

In vivo gene transfer: focus on the kidney

Renal gene transfer techniques are being developed as a novelexperimental approach to understand the pathogenesis of renaldisease and to potentially develop new therapeutic tools. Wereview the currently available technology to introduce foreigngenetic material into renal tissue, i.e., retroviral, adenoviral,and liposomal transfer systems with their respective advantagesand caveats. Today, the transfer efficiency of these methodsappears to be sufficiently high to study the effects of transducedgenes on renal function and morphology in rat kidney. This willallow (i) the elucidation of the function of genes on the courseof renal disease in experimental animal models and (ii) themodulation of local expression of endogenous genes which presumptivelycontribute to renal pathology in these models. One strategyto accomplish this aim is the use of recombinant DNA technologyto design antisense DNA constructs or oligonucleotides, whichinterfere with the renal expression of target genes. We willalso discuss some of the shortcomings of the currently usedtechniques with respect to potential therapeutic use of genetransfer systems and gene modulation.     

The National Occupational Research Agenda: a model of broad stakeholder input into priority setting.

OBJECTIVES: No single organization has the resources necessary to conduct occupational safety and health research to adequately serve the needs of workers in the United States. The National Institute for Occupational Safety and Health (NIOSH) undertook the task of setting research priorities in response to a broadly perceived need to systematically address those topics most pressing and most likely to yield gains to workers and to the nation. METHODS: NIOSH and its public and private partners used a consensus-building process to set priorities for the next decade for occupational safety and health research--the National Occupational Research Agenda. RESULTS: The process resulted in the identification of 21 research priorities grouped into 3 categories: disease and injury, work environment and workforce, and research tools and approaches. CONCLUSIONS: Although the field of occupational safety and health is often contentious and adversarial, these research priorities reflect a remarkable degree of concurrence among a broad range of stakeholders who provided input into a clearly defined and open process.     

In-vivo evaluation of random donor platelet concentrates from pooled buffy coats

 Random-donor platelet concentrates (PC) prepared from pooled buffy coats have recently been described as an alternative method for platelet preparation. We evaluated such PCs in the clinical setting compared with a standard PC from platelet apheresis. PCs were prepared either from pools of buffy coats (BC-PC) or from single donors (SD-PC) with the cell separator CS-3000 plus. PCs were stored for up to 5 days before transfusion. We compared fresh PC (day 1) with stored (day 2–3) and long-stored PC (day 4–5). For analysis, platelet increment in the recipient was determined immediately and 16–22 h (mean 20 h) after transfusion, corrected for total body area and transfused platelets (CCI). A total of 316 PCs were administered to 36 thrombocytopenic patients suffering from various hematological disorders. Patients with detectable HLA or platelet-specific antibodies or splenomegaly were excluded from the study. Mean platelet content of the PC was 262×10⁹ for BC-PC and 251×10⁹ for SD-PC. The 20-h CCI after transfusion of fresh PC was slightly higher with BC-PC than with SD-PC (14.5 versus 11.9;p=0.19), but values did not differ significantly between the two types of PC on any day of storage. For BC-PC, 20-h CCI decreased with further storage by 30% (10.2;p=0.02). For SD-PC a decrease by 9% was not significant. In conclusion, platelet concentrates prepared from pools of buffy coats showed excellent transfusion results when administered fresh, but storage decreased the CCI by 30%. No significant difference from PCs from plateletpheresis was observed on any day of storage. Both types of platelet concentrates were capable of sufficient platelet increment even when stored for up to 5 days. Received: 28 December 1995 / Accepted: 14 May 1996     

Composite indicators of dental health: functioning teeth and the number of sound-equivalent teeth (T-Health)

Abstract –This study investigated whether two new composite dental indicators -"the number of functioning teeth" and "the number of sound-equivalent teeth" are more efficient than the conventional DM FT index in revealing the social and behavioural factors which are significantly related to oral health status. The arbitrary set of weights given to the T-Health indicator was also evaluated. The number of functioning teeth was defined as the aggregate of filled (otherwise sound) and sound teeth. The T-Health was defined as a weighted average of sound teeth, filled (otherwise sound) teeth and teeth with some decay, the weights intended in principle to represent the relative amounts of sound tissue in these three categories of teeth. An arbitrary set of weights was used: 4, 2, and 1 for sound, filled, and decayed teeth, respectively. 164 families (father, mother and at least one 13-yr-old child) from Belo Horizonte, Brazil, were randomly selected from 13-yr-old children from private and state schools. The parents'ages ranged from 35 to 44 yr. Socio-economic status, area of residence, level of education, family income, sugar consumption, toothbrushing frequency and type of dental attendance were the social and behavioural oral health risk-factors considered in this study. The results indicated that the two new dental indicators are more sensitive to the influence of social and behavioural factors, such as those investigated here, than is the traditional DM FT index. A different set of weights (4, I, and I for sound, filled, and decayed) was suggested for the construction of the T-Health.     

Free rupture of the ascending aorta: successful resuscitation at a regional trauma center

After sustaining a free rupture of the intrapericardial ascending aorta secondary to blunt chest trauma, a 27-year-old man underwent successful aortic repair. To our knowledge, this is the first time a patient has ever survived this condition. Pericardial tamponade-together with rapid transport to the hospital and an aggressive surgical approach-was a key to the recovery of effective cardiac function and successful aortic repair. Although the patient succumbed to complications 74 days after surgery, this case illustrates the possibility of longterm survival after free rupture of the ascending aorta. The following report emphasizes the technical feasibility of controlling the perforated aortic root in such cases.     

Iodomethylated fatty acid metabolism in mice and dogs

The myocardial uptake of fatty acids labeled with radioactive iodine and injected i.v. can only be evaluated with SPECT if their oxidation kinetics is slow enough. For this reason, we evaluated different iodomethylated fatty acids in mice and dogs to determine which of them shows the highest myocardial uptake and the slowest oxidation. The most suitable was found to be 16-iodo-3-methyl hexadecanoic acid (mono ) since its myocardial fixation was the same as that of the reference, i.e. 16-iodo-9-hexadecenoic acid (IHA), whereas it was degraded more slowly. Thirty min after injection of mono into dogs, the decrease in myocardial activity with respect to the maximum was two fold less than after IHA injection. The myocardial uptake of the two dimethylated fatty acids studied, i.e. 16-iodo-2,2-methyl hexadecanoic acid and 16-iodo-3,3-methyl hexadecanoic acid, was less than that of IHA in mice and dogs. In the latter, the myocardial uptake was so small that we were unable to study the time course of its activity. Consequently, these dimethylated fatty acids are not suitable for the study of the myocardial uptake of fatty acids in man.