Apolipoprotein E*3-Leiden transgenic mice as a test model for hypolipidaemic drugs

PURPOSE: We report an investigation into the distribution of proteoglycans (PGs) in normal, organ-cultured and dextran-treated human corneas. METHODS: Immunogold labeling was carried out at the electron microscope level to localize keratan sulphate (KS), chondroitin sulphate (CS), and heparan sulphate (HS) PGs. RESULTS: High levels of labeling for CS was found in the epithelium, endothelium, and keratocytes, with light labelling present in the basement membranes and the corneal stroma. Labeling for HS was present in the epithelium, endothelium, and keratocytes, with intense labeling present at the endothelium/Descemet's membrane interface and the epithelium/Bowman's layer interface. Large filaments were also observed in these regions in cuprolinic blue-stained specimens. Keratan sulphate was present at high levels in the stroma and the basement membranes with low levels present within the keratocytes, epithelium, and endothelium. The pattern of KS labeling along the collagen fibrils in the stroma sometimes showed evidence of periodicity. Organ-cultured corneas had extensive collagen-free "lakes," the interior of which immunolabeled positively for KS and showed staining with cuprolinic blue. The lakes were greatly reduced in the dextran-treated samples. CONCLUSION: This investigation determined the ultrastructural distribution of KS, CS, and HS PGs in human cornea and showed that organ culture is associated with a change in distribution of stromal PGs.     

Serum antibodies reacting with subgingival species in refractory periodontitis subjects

The purpose of this investigation was to compare the levels of serum IgG antibody to 85 subgingival species in 32 refractory periodontitis, 56 successfully treated, and 33 periodontally healthy subjects. Refractory subjects showed mean full mouth attachment loss and/or >3 sites showing attachment loss >2.5 mm within 1 year after 2 treatment modalities, scaling and root planing and surgery plus systemically administered tetracycline. Successfully-treated subjects showed mean attachment level gain and no sites with attachment loss >2.5 mm, 1 year post-therapy. Periodontally healthy subjects exhibited no pocket or attachment level >3 mm, and no evidence of progressing attachment loss during 1 year of monitoring. Baseline serum was obtained from each subject and tested against 85 subgingival species, including reference strains and strains isolated from refractory subjects, using checkerboard immunoblotting. Significance of differences in levels of serum antibody among groups were sought using the Kruskal-Wallis test. Refractory subjects constituted a heterogeneous group based on their serum antibody response to subgingival species. Some individuals had antibody reactions to many subgingival species, while other subjects showed fewer or low numbers of responses. On average, refractory subjects exhibited higher numbers and levels of serum antibody reactions to a wide range of subgingival species than successfully treated or periodontally healthy subjects. Differences in serum antibody among clinical groups were more striking at higher threshold levels of antibody (>50 microg/ml and > 100 microg/ml). The data showed that a subject was 10.1 x more likely to be refractory if the subject exhibited antibody reactions with >9 subgingival species at >50 microg/ml (p<0.001, after adjusting for multiple comparisons). Serum antibody to a subset of the test species differed among the clinical groups. Porphyromonas gingivalis, Bacteroidesforsythus, and some strains isolated from refractory subjects (a novel Neisseria sp., Enterococcus faecalis, Prevotella loescheii and Prevotella oulora) elicited high serum antibody in the successfully treated and refractory subjects. High levels of serum antibody to a Microbacterium lacticum-like organism, Streptococcus oralis, Streptococcus constellatus, Actinobacillus actinonmycetemcomitans serotype c and Haemophilus aphrophilus significantly increased the likelihood of a subject being refractory to conventional periodontal therapy.     

Coronary artery fistula after cardiac transplantation

A cardiac transplant recipient with multiple coronary artery fistulae draining into the right ventricle is described. These fistulae presumably resulted from repeated endomyocardial biopsies. The diagnosis of coronary artery fistulae was made at the annual coronary arteriography. The magnitude of the shunt remained small over eight years of follow-up.     

Building memories: remembering and forgetting of verbal experiences as predicted by brain activity

A fundamental question about human memory is why some experiences are remembered whereas others are forgotten. Brain activation during word encoding was measured using blocked and event-related functional magnetic resonance imaging to examine how neural activation differs for subsequently remembered and subsequently forgotten experiences. Results revealed that the ability to later remember a verbal experience is predicted by the magnitude of activation in left prefrontal and temporal cortices during that experience. These findings provide direct evidence that left prefrontal and temporal regions jointly promote memory formation for verbalizable events.     

Optimization of hydrolysis of protein substrates by yeast proteases from Saccharomyces carlsbergenis

Maximizing efficiency of staff and resources is one method of reducing costs without affecting quality. Using a methodology similar to that used to maximize efficiency of airline-gate use, we developed a model with which to evaluate nursing support staff and clinical examining-room resources in a general otolaryngology clinic. For 144 patients over 7 consecutive clinic days, with four otolaryngologists and various combinations of support staff and examining rooms, we measured space and staff resource use, including total clinic time, number of patients seen, patient waiting time, physician and nurse productivity, and examining-room use. A simulation model was used as the medium of analysis to define parameters of the patient encounter. We identified optimal efficiency when there were three examining rooms and one and one-half nursing staff per physician or five examining rooms and three nursing staff for two simultaneously practicing physicians. Compared with a model of two rooms and one nursing staff member, our ideal model increased the percentage of the physicians' time spent in direct contact with patients from 84% to 92%. Visit length decreased from 81 minutes to 57 minutes, the average time from check-in to examination decreased from 47 to 16 minutes, and it became possible for three additional patients to be seen each day. Additional rooms and support staff, in comparison with the optimally efficient distribution, did not significantly affect these parameters. Maximizing efficiency with the use of this methodology can decrease waiting times for patients, resulting in greater patient satisfaction, improved physician productivity, total number of patients seen, and increased total contact time between physicians and patients.     

Should the presence of coiled blood flow in the left heart ventricle and aorta be taken into consideration when constructing artificial heart valves?]

This study presented the outcome of 92 EOC patients treated by platinum or platinum analogue with cyclophosphamide from January 1, 1993 to December 31, 1995. There were 77 evaluable patients. The follow-up ranged from 4-42 months (median 14 months). The over all 3-year survival was 64 per cent and the median progression-free interval was 16 months for the whole group. There was no significant difference in survival between patients who received cisplatin and those who received carboplatin (P = 0.093). Patients who underwent optimal debulking surgery had significantly longer progression-free interval (P = 0.001) than those who had sub-optimal surgery. Fifty four per cent of patients with clear cell carcinoma died of the disease. Patients who received cisplatin had a drop out rate while on therapy more often (24% vs 5.3%) than that of carboplatin. Toxicities from chemotherapy were moderate but manageable.     

Regenerating sciatic nerve does not utilize circulating cholesterol

Vascular endothelial growth factor (VEGF) is a major contributor to retinal neovascularization. The possible participation of VEGF and its high-affinity tyrosine kinase receptors, flk-1 and flt-1, in early background diabetic retinopathy was studied in the streptozotocin-induced diabetic rat model of experimental retinopathy using in situ hybridization, blotting techniques, and immunohistochemistry. Diabetic retinopathy was assessed by quantitative morphometry of retinal digest preparations. The number of acellular capillaries increased 2.7-fold in diabetic animals with diabetes' duration of 6 months compared with nondiabetic controls. VEGF expression was not detectable by in situ hybridization in nondiabetic rats but was highly increased in the ganglion cell layer and in the inner and outer nuclear layers of retinas from diabetic animals. VEGF protein was extractable only from diabetic retinas, and a strong immunolabeling was detected in vascular and perivascular structures. Increased flk-1 and flt-1 mRNA levels were also found in the ganglion cell and both nuclear layers of diabetic samples only. Dot blot and Western blot analyses confirmed the increase in flk-1 mRNA and protein in diabetic retinas. Also, flk-1 immunoreactivity was associated with vascular and nonvascular structures of the inner retinas from diabetic animals. These data obtained from a rodent model in which retinal neovascularization does not occur support the concept that the VEGF/VEGF receptor system is upregulated in early diabetic retinopathy.     

Health for all: analyzing health status and determinants

Several clinical disorders are strongly influenced by hormones involved in appetite and weight regulation. Obesity and eating disorders are of major importance, because they are associated with severe morbidity and considered to be among the greatest health problems in the Western world today. This review describes recent findings in hormonal regulation of food intake by substances acting both centrally, such as corticotropin-releasing factor, neuropeptide Y and leptin, and peripherally, such as cholecystokinin and somatostatin. Sex hormones and glucocorticoids play an important role in long-term regulation of metabolism. The role of these hormones in appetite and weight changes during life as well as during pregnancy and lactation is discussed. Furthermore, the development of obesity and eating disorders is influenced, in particular, by steroid hormones. Treatment with sex hormones, as in hormone replacement therapy, affects appetite and weight and may have beneficial effects in preventing android obesity. Currently, there is great effort in developing endogenous neurohumoral substances into effective drugs for the treatment of obesity and eating disorders. Leptin and neuropeptide Y analogues are of interest as potential antiobesity agents.     

Characterization and screening for mutations of the growth arrest-specific 11 (GAS11) and C16orf3 genes at 16q24.3 in breast cancer

BACKGROUND: Both fibroblast-mediated cytokine gene therapy and bone marrow transplantation (BMT) have proven to be efficient protocols for the recovery of bone marrow depression. In this report, the effects of fibroblast-mediated interleukin (IL)-6 gene therapy, in combination with BMT, on the recovery of irradiation-induced bone marrow depression were investigated. METHODS: NIH3T3 fibroblast cells engineered to secrete IL-6 (NIH3T3-IL-6) or NIH3T3 cells transduced with the neomycin gene (NIH3T3-Neo), in combination with 10(7), 10(6), or 10(5) syngeneic bone marrow cells, were implanted into irradiated mice. RESULTS: The platelets and white blood cells in the peripheral blood of the irradiated mice increased greatly 12 days after implantation of NIH3T3-IL-6 cells and BMT, the white blood cell counts were restored to a normal level 32 days after the combined therapy, and the platelet number was obviously higher than that in mice implanted with NIH3T3-Neo and BMT. Twenty and 25 days after the combined therapy, the mice showed accelerated recovery of colony-forming unit (CFU)-granulocyte/macrophages and CFU-megakaryocytes when compared with the mice implanted with NIH3T3-Neo cells and BMT. Ten days after lethal irradiation with gamma rays, the spleens formed more CFU-spleen in mice implanted with NIH3T3-IL-6 cells and BMT than in mice injected with phosphate-buffered saline or NIH3T3-Neo cells. Combined therapy with NIH3T3-IL-6 cell implantation and BMT delayed the survival period of the hematopoietic-depressed mice significantly when compared with therapy with NIH3T3-Neo cell implantation and BMT. CONCLUSIONS: These data demonstrated that the combined therapy of fibroblast-mediated IL-6 gene therapy and BMT could significantly promote the recovery of irradiation-induced hematopoietic depression.