The in vitro effect of vitamin D3 analogue EB-1089 on a human prostate cancer cell line (PC-3)

OBJECTIVES: To assess the impact of augmentation ureterocystoplasty on the success of cadaveric renal transplantation in children with dysfunctional bladders. METHODS: Two patients with end-stage renal failure secondary to dysfunctional bladders (one myelodysplasia and one posterior urethral valves) underwent augmentation ureterocystoplasty prior to renal transplantation in order to increase bladder capacity and improve compliance. RESULTS: Significant improvement of bladder storage function was achieved in both patients. By the use of megaureter for augmentation, untoward sequelae of enteric or gastric augmentation were obviated. Renal transplantation was successful in both patients. Both have normal renal function 4 and 3 years after transplantation. CONCLUSIONS: Renal transplantation into bladders previously augmented with megaureters is successful. The use of urothelial-lined biomaterial for augmentation avoids the potential complications of gastro- or enterocystoplasty, which are especially dangerous in transplant patients.     

The effect of actinomycin D on the formation of gametangia and mitosporangia in Allomyces

The effect of actinomycin on gametangium and mitosporangium production in Allomyces arbuscula and A. macrogynus has been investigated. Male gametangium production was not more sensitive to actinomycin than female development. Actinomycin at 20 mug/ml added at the commencement of induction was completely inhibitory. The process became insensitive to actinomycin just before the first septum was laid down.     

The effect of vitamin D supplementation on the bone mineral density of the femoral neck is associated with vitamin D receptor genotype

Recent studies suggest that variations of the vitamin D receptor (VDR) gene are related to bone mineral density (BMD). In this study, we examined the effect of vitamin D3 supplementation on BMD at the femoral neck in relation to VDR genotype. We analyzed 81 women, age 70 years and over, who participated in a placebo-controlled clinical trial on the effect of vitamin D3 supplementation (400 IU daily for at least 2 years) on BMD and fracture incidence. VDR genotype was based on the presence (b) or absence (B) of the BsmI restriction site. Mean BMD of the right and left femoral neck was measured at baseline and after 1 and 2 years. Dietary calcium, body mass index, and years since menopause were assessed at baseline while biochemical markers were measured at baseline and after 1 year. There was no difference among the BB, Bb, and bb genotype for baseline measurements of BMD at the femoral neck (mean and SD, g/cm2: 0.70 (0.10), 0.71 (0.12), and 0.69 (0.10), respectively), nor for any of the biochemical indices. The mean increase of BMD in the vitamin D group relative to the placebo group, expressed as percentage of baseline BMD, was significantly higher (p = 0.03) in the BB (delta BMD: 4.4%, p = 0.04) and Bb genotype (delta BMD: 4.2%, p = 0.007) compared with the bb genotype (delta BMD: -0.3%, p = 0.61). No significant changes were found for any of the other measured parameters. The VDR genotype-dependent effect of vitamin D supplementation in these elderly subjects suggest a functional involvement of VDR gene variants in determining BMD.     

The effect of growth and joint formation on bristle pattern in D. melanogaster

Dependence of bristle pattern on size and joint formation was studied for male first leg tarsi of fj (four jointed) and d (dachs) mutants in homozygotes and in mosaics resulting from X-ray induced mitotic recombination. Homozygotes have four tarsal segments, lacking a third tarsal joint in most cases. The two proximal segments are shortened, the first by one-third, and altered in bristle pattern, whereas the distal two segments are little affected. Expressivity of fj is high, and of d is low, for the extent and frequency of joint failure. The longer the second segment, the more complete the third joint and the greater the bristle number. Only the jointed side of the segment approximates two segments in its bristle pattern. Mosaic studies show that joint failure occurs autonomously in fj, or in the majority of d clones, and that joint formation by heterozygous clones is autonomous except in the border area contacting a fj or d spot lacking a joint, in which are a joint failure occurs. Bristle pattern in this jointless heterozygous area switches to that of a single segment. Localized non-autonomy also occurs in the t-rows of heterozygous tissue contacting a fj or d spot. Both mutant genes are interpreted as reducing longitudinal growth of the proximal tarsi, with joint failure as a consequence, and with alterations of bristle pattern resulting directly from size reduction, or indirectly through joint failure.     

The effect of the platelet-derived glycosaminoglycan serglycin on in vitro proplatelet-like process formation

The formation of proplatelet-like processes on megakaryocytes cultured in vitro has been shown to be inhibited by prothrombin, found residually in human serum, which is converted in culture to thrombin. This study reports that another factor found in human serum will counter this inhibition and permit proplatelet-like process formation to occur in vitro even in the presence of inhibitory concentrations of thrombin. The factor was purified from human platelet lysates and identified by amino acid sequence analysis as the proteoglycan serglycin. A similar, if not identical, factor was found at elevated levels in the plasma of thrombocytopenic rabbits. Serglycin probably functions as a proplatelet potentiator by virtue of a tendency to complex with thrombin. Thrombin in complex with serglycin retains its enzymatic properties, but is apparently sterically hindered from interacting with the megakaryocyte cell surface. In preliminary studies, the in vivo administration of serglycin in mice resulted in an increased number of circulating platelets when given in combination with interleukin-6 (IL-6).     

The effect of dietary vitamin D3 on the intracellular calcium gradient in mammalian colonic crypts

A physiological gradient in intracellular calcium ([Ca2+]i) has been hypothesized to exist along the colonic crypt base-mouth axis, which may be involved in the regulation of colonocyte proliferation, differentiation and apoptosis. In addition [Ca2+]i may be modulated by dietary vitamin D3 which is thought to be protective against colorectal cancer. CF1 mice were maintained for 6 weeks on a defined diet containing either high or low vitamin D3. A colonic crypt base-mouth [Ca2+]i gradient of 201 +/- 79 nM (mean +/- SEM, P < 0.05) was observed in animals maintained on a high vitamin D3 diet and was abolished in mice maintained on a low vitamin D3 diet. The [Ca2+]i gradient was independent of extracellular calcium and elevated levels of [Ca2+]i observed in the basal regions of the crypt in animals maintained on low levels of vitamin D3 were also associated with an increase in intracellular calcium stores. Therefore, a [Ca2+]i gradient exists in colonic crypts and is dependent on dietary vitamin D3.     

The study of child language in South Africa

This paper describes some of the research into child language that has been conducted in South Africa over the past 20 years. It is written from a clinical perspective and it describes the influence of changing demographic, social, educational and political variables on the study of child language. Specifically, the influence of the multilingual and multicultural nature of the society will be considered. Among issues discussed are the increasing research base on the acquisition of normal language, the adaptation of assessment tools and language in education.     

The causes of childhood blindness in South Africa

OBJECTIVES: 1. To ascertain the causes of severe visual impairment and blindness in children in schools for the blind in South Africa. 2. To determine the major avoidable causes. 3. To determine causation by ethnic group. DESIGN: A cross-sectional survey, undertaken at 15 of the 16 schools for the blind in South Africa, during May-September 1996, using standard WHO methodology. SUBJECTS: Children less than 16 years of age on May 1996. RESULTS: Of 1,615 eligible children, 1,311 were examined. According to WHO categories of visual impairment, using the corrected visual acuity in the better eye, 30.4% of children were blind (< 3/60, BL), 12.6% had severe visual impairment (< 6/60-3/60, SVI), 42.3% were visually impaired (< 6/18-6/60), and 12.0% had no impairment (6/18 or better). The anatomical sites of SVI/BL in 564 children were: retina 38.5%; optic nerve 15.2%; cornea/phthisis bulbi 11.0% and glaucoma 6.7%. Aetiological categories of SVI/BL were: hereditary diseases 33.0%; intra-uterine factors 0.9%; perinatal conditions 13.1%; acquired conditions of childhood 11.5%. In 41.5% the underlying cause could not be determined. In 38.8% of children with SVI/BL the cause was avoidable, i.e. preventable or treatable. The main causes varied between ethnic groups, the major difference being the higher proportion of retinopathy of prematurity in white and Indian children. CONCLUSIONS: The study suggests that 38.8% of causes of SVI or blindness in children in schools for the blind in South Africa are avoidable, and that specific control measures need to be targeted at different ethnic groups.     

The role of forensic dentistry in South Africa

Forensic dentistry has become an integral part of forensic medicine over the past 100 years. This has been due to the dedication of people like Amoedo, Gustafson, Sognaes, Keiser-Nielsen and Suzuki, to name but a few. They established the essential role which forensic dentistry plays mainly in the identification of human remains. Dental hard tissues are extremely resistant to fire and are usually the only remains after an extended period of burial. If antemortem dental records are available for an individual then dental identification is as certain as those of fingerprints. In South Africa forensic dentistry had its beginning in 1969 during the Windhoek air disaster. Since then there have been several cases of interest throughout the country, one of which was the crash of the Helderberg off the coast of Mauritius. Other aspects of forensic dentistry are the examination of bite marks and the recognition of facial trauma especially in cases of child abuse; the determination of age, sex and race of skeletal remains; dental ethics and jurisprudence as well as malpractice also form part of the duties of the forensic dentist. The five dental schools in South Africa each have a forensic team which is consulted on a regular basis by forensic pathologists and district surgeons. Forensic dentists are active members of the medicolegal team and should be consulted on a regular basis especially in cases where identification is concerned.     

Materials used by dental technicians in South Africa

Coronary heart disease and stroke are the commonest causes of illness and death for people living in the UK. We urgently need a better understanding of their aetiology. Recent research at the Medical Research Council's Environmental Epidemiology Unit is showing that impaired growth in fetal life and infancy have profound long-term consequences for health in adulthood. Improving maternal and infant health may be the key to effective prevention of cardiovascular disease in adult life.     

Vitamin D receptors and anti-proliferative effects of vitamin D derivatives in human pancreatic carcinoma cells in vivo and in vitro

The GER human pancreatic carcinoma cell line possesses receptors for 1,25-dihydroxyvitamin D3. We report that the vitamin D analogue EB 1089 inhibits the growth of these cells in vitro and when grown as tumour xenografts in immunodeficient mice. Tumour-bearing mice were given EB 1089 at a dose of 5 microg kg(-1) body weight i.p. thrice weekly for 4-6 weeks. Tumour growth was significantly inhibited in treated animals compared with controls in the absence of hypercalcaemia. These findings may have therapeutic implications in pancreatic cancer.     

Control of nuclear transcription of vitamin D-dependent genes by vitamin D

Contrary to the case with bacterial infections, progress in the diagnosis and treatment of invasive mycoses in cancer patients has been unsatisfactory. Amphotericin B deoxycholate has remained the drug of choice for severe invasive fungal infections for nearly 40 years. However, its infusion-related side effects, as well as its toxicity, may at times lead to dose reduction or early discontinuation of the treatment. The introduction of the new triazoles, fluconazole and itraconazole, has improved the therapeutic chances against several fungal infections; however, the need for a broad-spectrum drug in empiric antifungal therapy, the emergence of fluconazole-resistant Candida species, and the limitations of itraconazole in terms of speed action and erratic oral absorption represent important limitations. Recently, laboratory and clinical research has been directed at the development of new formulations of older classes of antifungals, the introduction of new classes of antifungals, and the use of immunomodulation associated with antifungal therapy. This paper reviews the more recent advances in the treatment of fungal infections in cancer patients.     

The effect of first season chemoprophylaxis in calves on second season pasture contamination and acquired resistance and resilience to gastrointestinal nematodes

Two groups of second grazing season cattle, which had been treated with an ivermectin-sustained-release bolus (ISRB) in their first grazing season, were monitored during consecutive years (1995 and 1996) on the same second grazing season pasture. In the preceding year (1994), this pasture had been grazed by yearlings that had not received chemoprophylaxis in their first grazing season. The objectives of the study were, firstly, to investigate whether the chemoprophylactic-treated yearlings were less resistant to gastrointestinal nematodes upon subsequent exposure, and hence excreted more strongyle eggs compared to the control yearlings; secondly, whether an increased susceptibility of the previously treated animals resulted in a yearly increase of the pasture infestation on the second grazing season pasture; and finally, whether this affected the second year weight gain of the animals. In 1996, the yearlings that had been chemoprophylactic-treated in 1995 excreted higher numbers of nematode eggs, compared to the previously 'untreated' yearlings. In addition, the proportion of Cooperia larvae was markedly higher in the faecal cultures from the chemoprophylactic treated-animals, suggesting a negative effect of preventive treatment with an ISRB on the acquired resistance of the animals. However, there was no evidence that the slightly higher egg output in the previously treated yearlings had an effect on the larval contamination of the second grazing season pasture. A significant yearly decrease in the second season average daily weight gains was observed, but it could not be inferred from the results of the parasitological parameters that the differences in second year growth were caused by different levels of resilience between chemoprophylactic-treated and -untreated animals. As the study covered three consecutive second grazing seasons, an effect of differences between years (e.g. in weather conditions or grass growth) on the results cannot be excluded.     

Lack of effect on ovariectomy on the metabolism of vitamin D and intestinal calcium-binding protein in female rats

A 20-year-old woman lost all useful vision over a 2 1/2-month period as a result of a necrotizing and occlusive vasculitis of the retina. Treatment with prednisone, immunosuppressants, and aspirin was unsuccessful. No systemic manifestations of the disease were found and no cause was discovered. Kodachromes and fluorescein angiograms showed the progression in one eye from normal to near total retinal necrosis. The process began with a mild venous dilation and peripheral arteritis that progressed into an obliterative vasculitis with abrupt vessel dilation, hemorrhages, and retinal swelling. This was followed by necrosis and sloughing of the retina into the vitreous. Vitreous contraction and necrotic retina produced unrepairable retinal detachments.     

The effect of excessive dietary vitamin A on performance and vitamin E status in swine fed diets varying in dietary vitamin E

A study was conducted to evaluate the effects of high dietary vitamin A on vitamin E status and performance of growing-finishing pigs fed diets supplemented with varying levels of vitamin E. Treatments consisted of corn-soybean meal-based diets supplemented with retinyl acetate to provide 2,000 or 20,000 IU of vitamin A/kg of diet and with DL-alpha-tocopheryl acetate to provide 0, 15, or 150 IU of added vitamin E/kg in a 2 x 3 factorial arrangement. The trial involved 84 crossbred pigs (26 kg initial BW) allotted to pens of two pigs each (one gilt, one barrow). Serum was obtained from all pigs on d 0, 3, 7, 21, 35, 63, and 77 of the 83- or 90-d feeding period. Tissue samples (liver, leg, and neck muscle, backfat, and leaf fat) were collected from one pig (barrow) in each pen at the end of the feeding period. Average daily gain and gain:feed were .93 kg and .30, respectively, without treatment differences (P > .10). Serum alpha-tocopherol increased linearly (P < .01) by d 3 with increasing level of dietary vitamin E supplementation. High dietary vitamin A resulted in a small decrease (P < .01) in serum alpha-tocopherol on d 3, but serum alpha-tocopherol concentration was not affected (P > .10) on other days. Tissue alpha-tocopherol increased linearly (P < .001) as dietary vitamin E increased in all tissues examined. No consistent evidence was found to indicate that a high level of dietary vitamin A interfered with performance or with blood serum or tissue alpha-tocopherol concentrations in growing-finishing swine.     

Effects of dietary vitamin D intake on plasma levels of parathyroid hormone and vitamin D metabolites in healthy Japanese

To clarify the nutritional status of vitamin D in Japanese, effects of dietary intake of vitamin D on plasma levels of intact and highly sensitive parathyroid hormone (I-PTH and HS-PTH), 25-hydroxyvitamin D (25-OH-D), 1,25-dihydroxyvitamin D (1,25(OH)2D), calcium (Ca) and phosphorus (P(i)) in 79 healthy Japanese were investigated. The plasma levels of 25-OH-D in men were significantly higher than those in women, whereas those of HS-PTH in men were significantly lower than those in women. The levels of 25-OH-D in men were generally higher than those in women. Significant correlations were observed between the dietary vitamin D intake and the plasma 25-OH-D or HS-PTH levels. Correlations between the plasma 25-OH-D levels and the plasma HS-PTH levels were also significant. These results suggest that dietary intake of sufficient amounts of vitamin D is effective for improving the vitamin D nutritional status through normalizing PTH levels.     

The direct and indirect costs of cardiovascular disease in South Africa in 1991

BACKGROUND: In South Africa, cardiovascular disease (CVD) is the leading cause of death among all population groups, other than blacks, among whom it ranks third. CVD therefore has a severe impact on the South African economy. OBJECTIVES: To ascertain the availability and quality of South African data on the cost of CVD and to estimate the impact of CVD on the South African economy during 1991. METHODS: The direct health care costs and the indirect costs related to loss of productivity were estimated. Where no direct or complete detailed South African data were available, projections were made based on reasonable assumptions of data and models developed in other countries; these were applied to the limited available South African data. The major disease outcomes considered for this cost estimation were: expenditure on ischaemic heart disease, cerebrovascular disease (stroke), venous thrombosis and embolism, and peripheral vascular diseases and related conditions. These diseases are responsible for the majority of fatal cases of CVD reported in South Africa. RESULTS: The estimated total cost of CVD in South Africa in 1991 was between R4.135 billion and R5.035 billion. This does not include the cost of rehabilitation and follow-up of CVD patients since the necessary data were not available to estimate it. About three-quarters of the direct health care costs were carried by the private sector. The direct health care costs were estimated to be approximately 42% of the total cost. The rest reflects the indirect cost of earnings foregone as a result of premature morbidity and mortality. CONCLUSION: To determine accurately the total economic burden of CVD on the South African economy, additional data will have to be collected. The estimated economic burden of CVD in South Africa clearly highlights the need for a broad-based population strategy, part of an overall national effort to prevent, diagnose and cost-effectively treat CVD.     

The transport of vitamin D and its 25-hydroxy metabolite in human plasma. Isolation and partial characterization of vitamin D and 25-hydroxyvitamin D binding protein

This study reports the isolation and partial characterization of vitamin D and 25-hydroxyvitamin D binding protein (DBP), the specific transport protein for vitamin D and its 25-hydroxy metabolite in human plasma. DBP was labeled by the addition of a tracer amount of 3H-labeled 25-OH-D3 to the original plasma used for protein fractionation. Previous experiments have shown that such 25-OH-D3 added in vitro binds to the same protein normally responsible for the transport of endogenous 25-OH-D and of vitamin D. The isolation of human DBP was achieved by an extensive sequence of procedures which resulted in a final yield of only approximately 4 mg of purified DBP from a starting volume of 34 liters of plasma. Purified DBP was homogeneous in the analytical ultracentrifuge and showed a single band of protein on analytical polyacrylamide gel electrophoresis. DBP had a sedimentation constant of 3.49s and a mol wt of approximately 52,000. The molecular weight was assessed by sedimentation equilibrium analysis and also by sodium dodecyl sulfate-disc-gel electrophoresis and by gel filtration on a standardized column of Sephadex G-150. The amino acid composition of DBP was determined and was generally consistent with the estimated extinction coefficient (E1cm1% at 280 nm) of about 9.1. The isoelectric point of DBP was estimated as 4.8 from isoelectric focusing experiments. Direct study of the binding capacity of the purified DBP for added 25-OH-D3 showed that the isolated DBP had a high affinity for 25-OH-D3, with an apparent maximum binding capacity of one molecule of 25-OH-D3 per molecule of protein.