Duct-associated lymphoid tissue (DALT) of minor salivary glands and mucosal immunity.

Minor salivary glands (MSG) play a substantial role in the secretory immunoglobulin A (sIgA)-mediated immunity of the oral cavity. There are two possibilities for the induction of this immunity: (i) an explicitly local antigenic stimulus, or (ii) a remote stimulus as part of the so-called 'common mucosal immune system'. This communication is an attempt to consolidate available evidence in support of both possibilities and to address the former in detail. Although there is strong circumstantial evidence supporting the feasibility of MSG functioning as a part of the common mucosal immune system, direct experimental evidence is yet to emerge. On the other hand, there is increasing structural and physiological evidence in support of MSG serving as a local immunological organ. The purely local response is attributed to the presence of MSG duct-associated lymphoid tissue (DALT), which is comparable to gut- or bronchial-associated lymphoid tissue (GALT or BALT) in origin, tissue organization and function. DALT is accessible to oral antigens by retrograde passage through MSG ducts. Repeated topical antigenic challenging via the oral mucosa may result in the appearance of interacinar plasma cells carrying specific homologous antibodies in MSG. Gut or enteric priming of the same antigen, by passing the oral mucosa by gastric intubation, need not evoke a remote immune response in MSG. Since DALT is more likely to occur in healthy, young growing individuals, who are less likely to undergo bioptic examination of MSG, it has not yet been documented in humans. The physiologically induced DALT is apt to be confused with focal accumulations of lymphoid tissue in pathologically altered MSG, as a consequence of local and some systemic autoimmune diseases. An attempt is made to demarcaate healthy and pathological MSG on the basis of currently available clinical, serological, immunological and genetic evidence.     

The effect of short-term intensive chemotherapy on reactivation of tuberculosis.

BACKGROUND: Various malignancies and cytotoxic chemotherapy have been proposed to increase the risk of reactivation of tuberculosis. Available literature to support this observation is still conflicting. There is scarcity of data from countries with rampant tubercular infection, such as India, in this regard. DESIGN AND METHODS: In the present retrospective analysis, patients with high-grade non-Hodgkin's lymphoma with past history of tuberculosis and have had adequate antitubercular therapy were identified from a Lymphoma Group study. These patients were followed up during cytotoxic chemotherapy and later to assess the risk of reactivation. RESULTS: A cohort of eight patients with past history of tuberculosis was selected from 141 patients of high-grade non-Hodgkin's lymphoma. The median age was 33.5 years (range, 24-53 years). Median duration between completion of antitubercular treatment and diagnosis of lymphoma was 5 years (range, 1.5-10 years). All patients received cyclical cytotoxic chemotherapy. The median duration of follow up after completion of chemotherapy was 5 years (range, 10 months to 5 years). None of these patients developed reactivation of tuberculosis. CONCLUSION: Cyclical chemotherapy for non-Hodgkin's lymphoma does not lead to reactivation of tuberculosis.     

Rheological characterisation of dextran-concanavalin A mixtures as a basis for a self-regulated drug delivery device.

The rheological characterisation of glucose sensitive mixtures containing dextran and concanavalin A (con A) with and without glucose, was undertaken using oscillatory rheometry at 20 and 37 degrees C so that comparative data could be gathered in the linear viscoelastic (LVE) range. Measurements for a series of mixtures showed that complex viscosity is a function not only of the con A concentration but of the content and molecular weight of the dextran used. The extent of liquefaction on addition of glucose also depended on these factors. The tan delta profiles confirmed the change from semi-solid towards fluid behaviour. This occurs when glucose effects dismantling of the three-dimensional structure of the dextran-con A system by competitive binding to the glucose receptors in the protein. For the mixtures studied, the changes occurred between contents of 0 and 1% (w/w) glucose at 20 and 37 degrees C and form a useful basis for the formulation of a self-regulating delivery device for the control of hyper-and hypoglycaemia in diabetes.     

Assessment of alcohol and other drug use behaviors in health professions students.

Alcohol and other drug (AOD) use behaviors of health professions students (HPS) were assessed by surveying both university-based HPS and other nursing programs in a Midwestern state in 1999. Response was 2,646 (56.4%) of surveyed students. Family history of alcohol-related and drug-related problems were reported by 39.8% and 13.9%, respectively, with 42.6% of respondents reporting one or both. Among nursing respondents, 48.1%, 19.2% and 51.1%, respectively, reported family problems with alcohol, drugs, or one or both. Past-year alcohol use was comparable to undergraduate college students (UCS) nationally (83%); heavy drinking, tobacco and recreational drug use by HPS were lower. Past year drug use was highest among medical students. Marijuana was the predominant illicit drug; medical students and males most often reported use. Health professions educational systems should proactively address student AOD prevention, education and assistance needs.     

Folate analogues. 33. Synthesis of folate and antifolate poly-gamma-glutamates by [(9-fluorenylmethoxy)oxy]carbonyl chemistry and biological evaluation of certain methotrexate polyglutamate polylysine conjugates as inhibitors of the growth of H35 hepatoma cells.

Representative examples of folate and antifolate poly-gamma-glutamyl metabolites were synthesized via the [(9-fluorenylmethoxy)oxy]carbonyl (Fmoc) chemistry using the KH polyamide resin. Polyglutamate yields were consistently better in all cases compared to the previous Merrifield method, and the crude products were obtained in greater than 85% purity. The symmetrical anhydride (7) derived from alpha-tert-butyl N-Fmoc-L-glutamate (6) was used for the initial coupling of the first glutamate residue to the KH resin and also for subsequent chain elongation. The alpha-tert-butyl protective groups were not labile under the conditions used for the cleavage of the finished peptide from the resin. A series of poly-gamma-glutamyl metabolites of methotrexate (MTX) with a chain length ranging from two to five glutamyl residues were synthesized and coupled with poly(L-lysine) having an average molecular weight of 27,000 and 52,000. Each conjugate was tested for its ability to inhibit the growth of wild type (H35) and MTX transport resistant (H35R) strains of hepatoma cells in culture, the latter having a 100-fold reduced sensitivity to MTX. 4-Amino-4-deoxy-N10-methylpteroylglutamyl-gamma-glutamylpoly (L-lysine) conjugate [MTX(G2)-poly-L-Lys-52000] and MTX(G4)-poly-L-Lys-52000 were among the most active (I50 = 8.0 and 10 nM against H35 cells) MTX-polylysines synthesized to date, and they were somewhat more inhibitory to the transport resistant cells. MTX(G5)-poly-L-Lys-52000 was approximately 1000 times more effective than MTX(G5)-poly-D-Lys-52000 in inhibiting the growth of H35R hepatoma cells in culture, indicating that internal cleavage of the gamma-glutamate chain of the conjugate with subsequent release of MTX or shorter chain polyglutamates of MTX is unlikely to be an important determinant of MTX-polyglutamate polylysine cytotoxicity. The results indicate that MTX-polyglutamate poly(L-lysine) conjugates are taken up by the cells independently of MTX and probably via endocytosis.     

Pharmacokinetics of orally administered norethisterone enanthate in rabbit, monkey, and women

Norethisterone enanthate (NET-En), an established intramuscular long-acting contraceptive agent, has previously been shown to be effective in inhibiting fertility in two rodent species even 4 days after oral ingestion. Pharmacokinetics of NET and NET-En were studied after oral and intramuscular doses in two animal species and a few women. The results suggest that the NET-En was absorbed within a day in all the species after oral dose. The estimates of relative bioavailability ranged from 13 to 51% in rabbits, monkeys, and women. The elimination half-life was 5–10 days. The presence of the active component, NET, in the circulation over the experimental period of 15 days suggests that NET-En could be useful as a long-acting oral pill. The suppression of progesterone levels during the luteal phase of menstrual cycle in women also supports this finding.     

Angiosarcoma of the pleura.

Angiosarcoma is a rare, highly malignant tumor arising from endothelial cells of small blood vessels. They usually occur in the skin, deep soft tissues, breast and liver. Pleural angiosarcomas are extremely rare and are restricted to case reports in medical literature. It is very difficult to distinguish them from malignant mesotheliomas on clinical, radiological and even histopathological features. Immunohistochemistry is valuable in making the diagnosis, showing negative reactivity for mesothelial markers and positivity for vascular markers. Prognosis is generally dismal except in occasional cases where the disease is localized and amenable for surgical resection. We report a 55-year-old man who presented to us with chest pain, cough and hemoptysis and was diagnosed to have a pleural angiosarcoma.