Brain myelination in the offspring of ethanol-treated rats: in Utero versus lactational exposure by crossfostering offspring of control, pairfed and ethanol treated dams

Pregnant Long-Evans rats were received on day 5 of gestation and divided into 4 treatment groups: (1) 27% calories provided as ethanol in a liquid diet; (2) pairfed i.e., isocaloric liquid diet restricted to match group (1); (3) liquid diet provided ad libitum; and (4) laboratory chow and water provided ad libitum. Litters were culled to 8 pups at birth and crossfostered across dams in all 4 groups to provide offspring falling into 16 different experimental groups, including some exposed to ethanol in utero only and some exposed only during lactation. At birth, blood alcohol levels of dams, culled pups and alcohol levels in the stomach contents of culled pups were measured. All pups were weaned and fed laboratory chow and water ad libitum from 21 days onward. At ages 16, 21, 30 and 52 days, pups were sacrificed, and organ/body weight ratios and brain myelin concentrations were determined. Ethanol treated dams had longer gestational periods. The offspring of ethanol treated dams which were crossfostered to pairfed and well nourished dams during lactation had delayed eye opening, persistent lag in body growth and slightly lower brain myelin concentrations. Offspring of dams which were either pairfed or well nourished during gestation, but crossfostered during lactation to ethanol treated dams, had abnormal organ weights, abnormal brain weights and severely depressed brain myelin concentrations persisting through 52 days of age. Thus, lactational ethanol effects on brain myelin were more severe than gestational effects; body growth was affected more severely by gestational exposure, and gestational effects were generally less severe with adequate nutrition.     

Isolation and partial biochemical characterization of an unknown polypeptide from white and grey brain material

White and grey matter have been purified from control brain by liquid column isoelectric focusing and chromatography on Sephadex G-75, and an unknown polypeptide, identified as h₃, isolated. Further investigation of this major brain fraction h₃ by several analytical methods shows that most probably it represents an independent chain with one disulphide bridge, composed of ± 220 amino-acid residues which are essentially hydrophobic on the amino-terminal side of the polypeptide. According to topographical localization h₃ seems to be ubiquitous in the brain, but till now it is impossible to determine whether it is brain specific or not, since its presence has not yet been investigated in other organs.     

Potentiation of apple procyanidin-triggered apoptosis by the polyamine oxidase inactivator MDL 72527 in human colon cancer-derived metastatic cells

Apple procyanidins have chemopreventive properties in a model of colon cancer, they affect intracellular signalling pathways, and trigger apoptosis in a human adenocarcinoma-derived metastatic cell line (SW620). In the present study we investigated relationships between procyanidin-induced alterations in polyamine metabolism and apoptotic effects. Apple procyanidins diminish the activities of ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase, key enzymes of polyamine biosynthesis, and they induce spermidine/spermine N(1)-acetyltransferase, which initiates retroconversion of poly-amines. As a consequence of the enzymatic changes polyamine concentrations are diminished, and N(1)-acetyl-polyamines accumulate in SW620 cells. In contrast with expectations MDL 72527, an inactivator of polyamine oxidase (PAO), improved the anti-proliferative effect of procyanidins, and caused an increase of the proportion of apoptotic cells, although it prevented the formation of hydrogen peroxide and 3-acetamidopropanal, the cytotoxic products of PAO-catalysed degradation of N(1)-acetylspermidine and N1-acetylspermine. Addition of 500 microM N1-acetylspermidine to the culture medium in the presence of procyanidins mimicked the effect of MDL 72527. Therefore we presume that the enhanced procyanidin-triggered apoptosis by MDL 72527 is mediated by the accumulation of N(1)-acetyl-polyamines. The observation that apple procyanidins enhance polyamine catabolism and reduce polyamine biosynthesis activity similar to known inducers of SSAT, without sharing their toxicity, and the potentiation of these effects by low concentrations of MDL 72527 suggests apple procyanidins for chemopreventive and therapeutic interventions.     

Continuous infusion interleukin-2 and intravenous famotidine in metastatic melanoma

Lymphokine-activated killer cell (LAK) cytotoxicity against tumor cells is induced by the use of high-dose infusional interleukin-2 (IL-2). LAK cytotoxicity against neoplastic cells may be augmented by famotidine. Twelve (12) patients have been treated with continuous infusion IL-2 (18 MIU/m2/24 hours) for 72 hours and famotidine 20 mg IVPB twice per day. Cycles were repeated every 3 weeks. These patients were of median age--67 years (range, 25-79), had a median performance status of 1 (range, 0-1), and had metastatic sites, including lung, lymph node, subcutaneous/soft tissue, and liver. The most common toxicities of this regimen were fever, rigors, nausea/emesis, hypophosphatemia, and hypomagnesemia. Three (3) partial responses have been seen (25% response rate). One (1) of these responders has undergone complete surgical resection and is disease-free at 15+ months. Four (4) patients are alive at a median of > 25 months. The median survival for all patients is 13 months. This combination of infusional IL-2 with famotidine is active in metastatic melanoma.     

Going home from hospital: the postdischarge experience of patients and carers in rural and remote Queensland

OBJECTIVE: This paper reports on a study of the experiences of patients and carers discharged from the Townsville General Hospital into rural and remote communities in North Queensland. DESIGN: The findings presented in this paper are drawn from post-discharge in-depth, qualitative interviews of both patients and carers. RESULTS: The findings indicate the importance of examining the lived experience of both patients and carers in attempting to understand the impact of current discharge practices. CONCLUSION: We conclude that carers are providing the bulk of post-discharge care of patients - a difficult role in which the difficulties are exacerbated when the patient or the carer or both is a long way from the home community.     

Behavior of the GABIE, 3M 3500, PerkinElmer Tenax TA, and RADIELLO 145 diffusive samplers exposed over a long time to a low concentration of VOCs

Diffusive sampling is particularly suited to determine time-weighted average volatile organic compound (VOC) concentration in occupational hygiene and environmental air monitoring. The purpose of this study was to measure the sampling rate variation of four different samplers in a special use--the exposure to a low concentration of volatile organic compound (10 to 200 ppb) for a long period (1 to 14 days). PerkinElmer tube-type adsorbent was packed with Tenax TA and RADIELLO cartridge packed with Carbograph 4. Badge-type activated carbon diffusive samplers 3M 3500 and GABIE were exposed to the same controlled atmospheres of benzene as meta-xylene (BTX) during the same exposure times. Performance samplers were observed for variability of uptake rates according to concentration levels, exposure duration, back diffusion, and competition phenomena at the adsorption sites. Particular benzene behavior has been noted for the thermally desorbable tube-type diffusive sampler: the measured sampling rates decrease with time following an exponential profile. With badge-type active charcoal diffusive samplers, the uptake rates were found to be highly stable and unaffected by time exposure. Overall, in the region of a few tens of ppb, for long-time exposure and for the lightest compounds, 3M 3500 and GABIE diffusive samplers seem the most appropriate diffusive sampling technique in terms of performance and facility in use.     

Characterization of endogenous human promyelocytic leukemia isoforms

Promyelocytic leukemia (PML) has been implicated in a variety of functions, including control of TP53 function and modulation of cellular senescence. Sumolated PML is the organizer of mature PML bodies, recruiting a variety of proteins onto these nuclear domains. The PML gene is predicted to encode a variety of protein isoforms. Overexpression of only one of them, PML-IV, promotes senescence in human diploid fibroblasts, whereas PML-III was proposed to specifically interact with the centrosome. We show that all PML isoform proteins are expressed in cell lines or primary cells. Unexpectedly, we found that PML-III, PML-IV, and PML-V are quantitatively minor isoforms compared with PML-I/II and could not confirm the centrosomal targeting of PML-III. Stable expression of each isoform, in a pml-null background, yields distinct subcellular localization patterns, suggesting that, like in other RBCC/TRIM proteins, the COOH-terminal domains of PML are involved in interactions with specific cellular components. Only the isoform-specific sequences of PML-I and PML-V are highly conserved between man and mouse. That PML-I contains all conserved exons and is more abundantly expressed than PML-IV suggests that it is a critical contributor to PML function(s).     

Differences of pancreatic expression of 7B2 between C57BL/6J and C3H/HeJ mice and genetic polymorphisms at its locus (Sgne1)

C57BL/6 (B6) mice develop glucose intolerance with age, whereas C3H/He (C3H) mice do not. In this study, we examined whether this differential glucose homeostasis was associated with differences of proteolytic activation of pancreatic prohormones. Radioimmunoassays showed comparable levels of fasting plasma insulin between the two strains but a significantly lower glucagon level in B6 mice. Pulse-chase analysis of glucagon biosynthesis in isolated pancreatic islets revealed that proglucagon was less efficiently processed in B6 mice. Because proprotein convertase (PC)2 and its 7B2 helper protein are required for this processing, we quantified islet mRNA levels by RT-PCR and protein levels by immunoblotting. The levels of proPC2 mRNA were similar between the two strains, but B6 protein extracts contained less of the mature PC2. In contrast, 7B2 mRNA and protein levels were both significantly lower in B6 pancreas. Sequencing of the 7B2 gene promoter and cDNA in the two strains revealed seven single nucleotide polymorphisms and one dinucleotide insertion/deletion in the cDNA as well as a single nucleotide polymorphism and two insertions/deletions in the promoter. Differential expression of 7B2 may contribute to the difference between B6 and C3H mice not only in glucagon production and secretion but also in glucose tolerance.