Anti-IgM induces transforming growth factor-beta sensitivity in a human B-lymphoma cell line: inhibition of growth is associated with a downregulation of mutant p53

We wished to examine the role of transforming growth factor-beta (TGF- beta) in the regulation of human lymphoma cell growth. The RL cell line is an immunoglobulin M (IgM)+, IgD+ B lymphoma cell line, which does not constitutively express receptors for TGF-beta, and thus has lost the ability to respond to the inhibitory effects of TGF-beta. We demonstrate here that anti-Ig antibodies can efficiently upregulate the expression of TGF-beta receptors and promote sensitivity to growth inhibition by TGF-beta. Furthermore, because TGF-beta has been shown to function in late G1 of the cell cycle, we examined the ability of TGF- beta to modulate two tumor suppressor proteins known to be critical regulators of the G1/S transition, Rb and p53. Rb is a 105- to 110-kD phosphoprotein, which has been shown to maintain its growth suppressive function when it is found in the hypophosphorylated state. Wild-type p53 is a 53-kD phosphoprotein that appears to be important in preventing cell-cycle progression and promoting apoptosis in cells with DNA damage, whereas mutant p53 can overcome those functions. We show here that TGF-beta treatment of phorbol myristate acetate (PMA) or anti- Ig-activated RL cells results in growth inhibition through a dual effect on Rb and mutant p53. After TGF-beta treatment, we observe a predominance of Rb in the hypophosphorylated, growth suppressive form. In addition, we show a decrease in levels of mRNA and protein for mutant p53. We also show that, although these changes are sufficient to halt progression through the cell cycle, the cells do not appear to undergo extensive programmed cell death following 72 hours of TGF-beta treatment. Thus, although these lymphoma cells maintain the capacity to be negatively growth regulated by TGF-beta, the ability of TGF-beta to induce apoptosis must be independently controlled.     

Biochemical and immunological studies on isolated brush border membranes of human kidney cortex and their membrane surface proteins

An automated fluorometric microassay of homovanillic acid (HVA), the main metabolite of Dopamine is described herein. A small volume (0.4 ml) of biological extracts can be determined in the concentration range of 10–2500 ng/ml. Sixty samples per hour can be passed through this continuous flow system with good reproducibility. Several factors modifying the fluorophore formation are studied. The concentration of HVA in human cerebrospinal fluid (CSF) was estimated with this system before and after Probenecid administration.     

Screening of an elderly female population for hypo- and hyperthyroidism by use of a thyroid hormone panel

The elderly female population living in a rural primary health care district in the south of Sweden was screened for hypo- and hyperthyroidism. A total of 1 442 (97.3%) of the 1 482 women 60 years of age or older attended the study. By use of a computer-evaluated thyroid hormone panel, 178 women (12.3%) were identified as probably abnormal. Among them, 8 women (0.55% of total) with previously unknown thyroid disease were detected as overtly hypothyroid. If also 13 women with spontaneous subclinical hypothyroidism were included, the prevalence of earlier unknown hypothyroidism was 21/1 442 (1.5%). The number of subjects with hyperthyroidism discovered by screening was 28/1 442 (1.9%). Although much remains to be elucidated regarding medical, social and economic factors, the high figures obtained for newly discovered abnormal thyroid function suggest that screening for hyper- and hypothyroidism may be worthwhile in such an elderly female population.     

Communities' views on prerequisites for collaboration between modern and traditional health sectors in relation to STI/HIV/AIDS care in Zambia

Traditional, complementary and alternative medicine (TM/CAM) is globally increasing in popularity. The World Health Organization (WHO) has advocated for the integration of TM/CAM in national public health policies to enhance health care resources. Interest in collaboration between traditional and biomedical health sectors has been renewed in attempts to strengthen control of the AIDS epidemic. However, studies exploring communities' views on the prerequisites for such collaboration are inexistent. We conducted 21 focus group discussions with community members in two Zambian urban centres (Ndola and Kabwe) to explore their perspectives on preconditions for useful collaboration between traditional and modern health workers in the management of STIs and HIV/AIDS. This study shows that laypersons' perspectives can be rich and inform complex policy issues. Five categories indicating key areas of actions were identified, including protection of traditional medicine and of compensation of healers, education of both groups of providers and adequate community involvement. The respect for some degree of secrecy in traditional medicine was also called for. As part of efforts to strengthen available resources for better care of STI/HIV/AIDS, this study provides policymakers, researchers and practitioners with an outline of fundamentals in terms of needed crucial changes at health policy level, among providers and in the community for sustainable collaboration between modern and traditional health practitioners.     

Lead accumulation in tidemark of articular cartilage

OBJECTIVE: Determination of the spatial distribution of the toxic element lead (Pb) and other trace elements in normal articular cartilage and subchondral bone from adult humans with no history of work-related exposure to Pb. METHODS: Four macroscopically normal femoral heads and three patellas were harvested from randomly selected forensic autopsies. All subjects died of acute illnesses, had no history of work-related exposure to Pb and had no metabolic bone disease. The elemental distribution of lead (Pb) together with zinc (Zn), strontium (Sr) and calcium (Ca) in the chondral and subchondral region was detected using high resolution synchrotron radiation induced micro X-ray fluorescence (SR mu-XRF) analysis. SR mu-XRF line scans in conventional and SR mu-XRF area scans in confocal geometry were correlated to backscattered electron (BE) images visualizing the mineralized tissue. RESULTS: In all samples, we found a highly specific accumulation of Pb in the tidemark, the transition zone between calcified and non-calcified articular cartilage. Pb fluorescence intensities in the tidemark, which is thought to be a metabolically active mineralization front, were 13-fold higher when compared to subchondral bone. Pb intensities in the subchondral region were strongly correlated with Zn, but were distinctly different from Ca and Sr. CONCLUSIONS: The finding of the highly specific accumulation of lead in the tidemark of human articular cartilage is novel. However at this point, the exact mechanisms of the local Pb accumulation as well as its clinical implications are unknown.     

Use of complementary and alternative medicine in the Scandinavian countries

OBJECTIVE: To describe the prevalence of use of complementary and alternative medicine (CAM) in Norway, Denmark and Stockholm County. DESIGN, SETTING, AND SUBJECTS: In Norway, a national representative sample of 1000 participants completed telephone interviews regarding their CAM use in 1997 (response rate 51). In Denmark, a national representative sample of 16 690 participants completed questionnaires and interviews regarding their health and morbidity in 2000 (response rate 74). In Stockholm County, a randomly selected sample of 1001 participants completed telephone interviews about their CAM use in 2000 (response rate 63). RESULTS: Prevalence of ever-use of CAM was 34% in Norway, 45% in Denmark, and 49% in Stockholm. Use of CAM is associated with poor self-reported health in all three studies, and with visits to a medical doctor in Denmark and Norway. More women than men, and more with higher education, reported use of CAM. Most frequently used CAM therapy was homeopathy in Norway, reflexology in Denmark, and massage in Stockholm County. CONCLUSIONS: Use of CAM is common in the Scandinavian countries, and there are national differences regarding therapy preferences. Many individuals use both CAM and conventional health services.