Magnesium-fluoride interrelationships in man II. Effect of magnesium on fluoride metabolism

The effect of magnesium on the fluoride balance was investigated in man by determining metabolic balances of fluoride and magnesium in control studies and during magnesium supplementation. The magnesium intake averaged 264 mg/day in the control studies and 825 in the experimental studies. The studies were carried out during four calcium intakes that ranged from 200 to 2,200 mg/day and during phosphorus intakes ranging from 800 to 2,000 mg/day. The studies were carried out during a fluoride intake of about 4 mg/day that was due to the dietary fluoride content and the intake of water and during a high fluoride intake of 25 mg/day that was due to the addition of sodium fluoride. During the high magnesium intake, both the urinary and fecal magnesium excretions increased and the magnesium balances became more positive. These changes were not associated with any significant changes of either the urinary or fecal fluoride excretions or of the fluoride balances during the different intakes of calcium phosphorus, or fluoride.     

Regulation of the association between PSTPIP and CD2 in murine T cells

Prominent in T cells and natural killer cells, CD2 binding protein 1 (CD2BP1) plays an important role in CD2-mediated adhesion and signal transduction. In the current study, we investigated CD2 and PSTPIP (proline, serine, threonine phosphatase interacting protein, murine homologue of CD2BP1) interactions in purified mouse splenic T cells. PSTPIP associated with CD2 in both resting and activated T cells. Following various stimuli, such as concanavalin A, anti-TCRbeta, anti-CD3epsilon, anti-CD3epsilon/phorbol myristate acetate (PMA), IL-2, or PMA/ionomycin, PSTPIP and CD2 expression, as well as their association, increased in a time-dependent fashion. While PSTPIP expression and CD2 expression were comparable across most groups, the PSTPIP-CD2 association stimulated by anti-CD3epsilon alone was significantly greater than with other stimuli. Stimulation by anti-CD3epsilon plus anti-CD28 induced even greater PSTPIP-CD2 association than anti-CD3epsilon treatment alone, indicating that CD28 initiated signals are involved in regulating this interaction. There was no direct association between CD3epsilon or CD28 and PSTPIP. Tyrosine phosphorylated PSTPIP bound poorly to CD2 compared to dephosphorylated PSTPIP, and protein tyrosine phosphatase was shown to affect both phosphorylation of PSTPIP and the CD2-PSTPIP association. In addition to CD2, PSTPIP associated with CD4, CD8, CD54, and CD62L. CD2 and CD4 ligation reciprocally regulated their association with PSTPIP. These findings indicate that T cell activation, particularly through the CD3 and CD28 signal transduction pathways, regulates PSTPIP-CD2 interactions. PSTPIP likely has additional broader effects through interactions with CD4, CD8, CD54, and CD62L, and this may influence T cell responses to antigen.     

Pulmonary atypical carcinoid: predictors of survival in 106 cases

Pulmonary neuroendocrine tumors (NE) include a spectrum of tumors from typical carcinoid (TC) to atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCLC). Little is known about prognostic predictors for AC because of its rarity. Survival analysis was performed on 106 ACs with clinical follow-up from the AFIP and the Pathology Panel of the International Association for the Study of Lung Cancer (IASLC). The tumors fulfilled the 1999 WHO/IASLC criteria for AC of a NE tumor with a mitotic rate of 2 to 10 per 2 mm(2) of viable tumor or coagulative necrosis. Multiple clinical and histologic features were analyzed by Kaplan-Meier and Cox regression analysis. Of the clinical features, higher stage (P = .003) and a tumor size of 3.5 cm or greater (P = .003) were associated with a worse prognosis. Features that were histologically unfavorable by univariate analysis were mitotic rate (P =.002), pleomorphism (P = .018), and aerogenous spread (P =.007). Histologically favorable features by univariate analysis were the presence of palisading (P = .008), papillary (P = .039), pseudoglandular (P =.026), and rosette (P = .022) patterns. Female gender showed a trend toward a poorer prognosis (P =.085) and was included in the multivariate model. Multivariate analysis stratified for stage showed mitoses (P<.001), a tumor size of 3.5 cm or greater (P =.017), and female gender (P =.012) to be the only negative independent predictors of prognosis and the presence of rosettes (P = .016) to be the only independent positive predictor. We further divided the AC into subgroups of low (2 to 5 mitoses/2 mm(2)) and high (6 to 10 mitoses/2 mm(2)) mitotic rate and compared the survival with TC and with LCNEC. Within the category of AC, the patients with a higher mitotic rate had a significantly worse survival than those with a lower mitotic rate (P<.001) stratified for stage. Five- and 10-year survival rates for AC (61% and 35%, respectively) stratified for stage were significantly worse than for TC and better than that for LCNEC and SCLC. Chemotherapy or radiation therapy was given in 12 of 52 and 14 of 52 cases, respectively, but the data were insufficient to evaluate tumor response. We conclude that AC is an aggressive neuroendocrine neoplasm with survival intermediate between TC and LCNEC and SCLC. Higher mitotic rate, tumor size of 3.5 cm or greater, female gender, and presence of rosettes are the only independent predictors of survival. Surgical resection remains the treatment of choice, and the role of chemotherapy and radiation therapy remains to be proven.     

Resistance of chicks and poults fed vermicompost to caecal colonization by Salmonella

Vermicompost (VC) was produced by feeding the earthworm Eisenia foetida vegetable matter and fresh faeces from adult specific pathogen-free chickens. This was used as a competitive exclusion treatment for chicks and poults against challenge with Salmonella spp. One-day-old chicks and poults housed in floor pens, were treated with VC sprinkled on feed on days 1 and 2. For studies with Salmonella typhimurium, chicks were challenged on day 5 by either oral inoculation with 10(4 )colony-forming units (CFU) or by contact transmission and killed 7 to 9 days later. In four trials, conducted on a total of 412 VC-treated and 275 control chicks, and in one trial with about 40 poults per group, treatment with VC significantly reduced (P<0.01) caecal colonization by 5. typhimurium. For experiments with Salmonella enteritidis, chicks were challenged orally with 10(5 )CFU and kept in isolators on wire floors. They were also significantly protected (P<0.01) against caecal colonization by VC-treatment. In addition, in one trial S. enteriditis was isolated by enrichment techniques from the livers of nine of 10 non-treated and one of 39 VC-treated chicks.     

Phenotypic mixing between reticuloendotheliosis virus and avian sarcoma viruses.

Coinfection of chicken embryo fibroblasts with reticuloendotheliosis virus (REV) and avian sarcoma virus leads to the formation of avian sarcoma viral pseudotypes which carry envelope determinants of REV. These pseudotypes can be neutralized by REV antiserum, have a host range which is different from that of any known avian sarcoma virus, and are unable to form foci in cells preinfected with REV. The REV stocks used in these experiments were plaque-purified. They were free of avian leukosis virus detectable in the COFAL tests, and their ability to form pseudotypes with avian sarcoma virus was neutralized with specific REV antiserum.     

Progestagen-releasing vaginal rings--an update

Marketing of an intravaginal ring that releases a progestagen at low dosage willbegin in 1985. The device is a silicone rubber toroidal ring 55.6 mm in diameter. Its active constituent is 5 mg of levonorgestrel, with an in vivo release rate of 20 mcg/day. The device is left in the vagina for 3 months, at which point a new ring is fitted. The device largely acts locally on the genital tract, altering cervical mucus so that it is relatively inpenetrable to sperm. Over 50% of cycles in device acceptors are ovulatory; 19% have inadequate luteal function and 29% are anovulatory. In a social acceptability study involving 27 ring users, all participants asserted at the 8 week follow up that the ring was the best method they had used and indicated an interest in continuing to use the device. Over 50% cited health reasons for this choice. The ring was viewed as less invasive than the IUD and more convenient than the diaphragm. The greatest criticism of the ring resulted from changed menstrual patterns; in most cases, however, it was the unexpectedness of the change rather than the change itself that concerned the user. Clinical trials have suggisted that the ring is viable in terms of its safety, efficacy, and overall acceptability. The pregnancy rate in 5500 woman-months of experinence stands at 3%, and there has been no evidence of an increased incidence of actopic pregnancy. Although 20% of women experienced expulsion of the device, only 2% discontinued use for thes reason. The continuation rate of 60% after 1 year's use compares favorably with other methods of hormonal contraception.