Menin, the product of the MEN1 gene, is a nuclear protein

The MEN1 gene, mutations in which are responsible for multiple endocrine neoplasia type 1 (MEN1), encodes a 610-amino acid protein, denoted menin. The amino acid sequence of this putative tumor suppressor offers no clue to the function or subcellular location of the protein. We report herein, based on immunofluorescence, Western blotting of subcellular fractions, and epitope tagging with enhanced green fluorescent protein, that menin is located primarily in the nucleus. Enhanced green fluorescent protein-tagged menin deletion constructs identify at least two independent nuclear localization signals (NLS), both located in the C-terminal fourth of the protein. Among the 68 known independent disease-associated mutations, none of the 22 missense and 3 in-frame deletions affect either of the putative NLS sequences. However, if expressed, none of the truncated menin proteins resulting from the 43 known frameshift/nonsense mutations would retain both the NLSs. The precise role(s) of menin in the nucleus remain to be understood.     

Systolic blood pressure trends in US adults between 1960 and 1980: influence of antihypertensive drug therapy

Recent blood pressure trends reflect progress in hypertension control, but prevalent drug therapy precludes direct estimation of the component due to primary prevention. In data gathered on persons aged 35-74 years in three successive US health examination surveys (1960-1980), systolic blood pressure levels assuming no drug therapy were imputed by reassigning blood pressure to the upper end of the distribution for respondents reporting use of antihypertensive medication. Blood pressure was partitioned into four ordinal categories based on weighted percentiles of the 1960-1962 distributions for 35- to 44-year-old males and females who reported no use of antihypertensive medication. Cumulative logit models (alpha = 0.01) were used to estimate age- and sex-specific trends for blacks and whites within two strata (<25 or > or =25) of body mass index (BMI) (weight (kg)/height (m)2). Before imputation, systolic blood pressure decreased between 1960 and 1980; after imputation, significant decreases remained only in 35- to 44-year-olds. Strong associations of black race and BMI > or =25 with higher blood pressures were present in models with and without drug therapy. Thus, according to the models, there has been little progress in decreasing racial or BMI-related blood pressure differentials. Above the age of 44 years, blood pressure trends were largely attributable to medication use. In contrast, data for 35- to 44-year-olds suggest progress in primary prevention.     

Independent isolates of the emerging subgroup J avian leukosis virus derive from a common ancestor

A new subgroup of avian leukosis virus (ALV) that includes a unique env gene, designated J, was identified recently in England. Sequence analysis of prototype English isolate HPRS-103 revealed several other unique genetic characteristics of this strain and provided information that it arose by recombination between exogenous and endogenous virus sequences. In the past several years, ALV J type viruses (ALV-J) have been isolated from broiler breeder flocks in the United States. We were interested in determining the relationship between the U.S. and English isolates of ALV-J. Based on sequence data from two independently derived U.S. field isolates, we conclude that the U.S. and English isolates of ALV-J derive from a common ancestor and are not the result of independent recombination events.     

Increased transversions in a novel mutator colon cancer cell line

We describe a novel mutator phenotype in the Vaco411 colon cancer cell line which increases the spontaneous mutation rate 10-100-fold over background. This mutator results primarily in transversion base substitutions which are found infrequently in repair competent cells. Of the four possible types of transversions, only three were principally recovered. Spontaneous mutations recovered also included transitions and large deletions, but very few frameshifts were recovered. When compared to known mismatch repair defective colon cancer mutators, the distribution of mutations in Vaco411 is significantly different. Consistent with this difference, Vaco411 extracts are proficient in assays of mismatch repair. The Vaco411 mutator appears to be novel, and is not an obvious human homologue of any of the previously characterized bacterial or yeast transversion phenotypes. Several hypotheses by which this mutator may produce transversions are presented.     

Definition of natural T cell antigens with mimicry epitopes obtained from dedicated synthetic peptide libraries

Progress has recently been made in the use of synthetic peptide libraries for the identification of T cell-stimulating ligands. T cell epitopes identified from synthetic libraries are mimics of natural epitopes. Here we show how the mimicry epitopes obtained from synthetic peptide libraries enable unambiguous identification of natural T cell Ags. Synthetic peptide libraries were screened with Mycobacterium tuberculosis-reactive and -autoreactive T cell clones. In two cases, database homology searches with mimicry epitopes isolated from a dedicated synthetic peptide library allowed immediate identification of the natural antigenic protein. In two other cases, an amino acid pattern that reflected the epitope requirements of the T cell was determined by substitution and omission mixture analysis. Subsequently, the natural Ag was identified from databases using this refined pattern. This approach opens new perspectives for rapid and reliable Ag definition, representing a feasible alternative to the biochemical and genetic approaches described thus far.     

Adolescent sexual and reproductive behavior: a review of the evidence from India

Despite the fact that adolescents represent almost one quarter of the Indian population, their reproductive health needs are poorly understood and ill served. This paper documents the existing research on sexual and reproductive health, explores the knowledge and attitudes among this population in India, and highlights limitations of methodologies currently employed in research on adolescent reproductive health in India. One serious limitation is the lack of attention in almost every dimension of their reproductive health, including sexuality, reproductive morbidity, abortion-seeking and reproductive choice. What is needed is more behavioral research that explores the levels, patterns, and sociocultural factors underlying adolescents' reproductive health; assesses adolescent reproductive health needs and ways in which health and information services can be structured to respond to these needs in light of the social, cultural and economic constraints that adolescents face; and explores appropriate methodological alternatives, recognizing the need for community-based research, as well as the difficulties of conducting such research under the sociocultural constraints prevailing in India. At the same time, this review argues for far more attention within programs to address adolescent reproductive health service and information needs.     

A concise synthesis and in vitro cytotoxicity of new labdane diterpenes

A new series of labdane-related diterpenes have been synthesized from (-)-sclareol and assayed in vitro cytotoxicity against mouse and human cancer cells. A key intermediate, homodrimane and furanolabdane derivatives show good in vitro cytotoxicity comparable to those of mitomycin C and adriamycin.     

Waldenstr?m''s macroglobulinemia resulting from localized gastric lymphoplasmacytoid lymphoma

Arthritis may be the presenting manifestation of iron overload. The metacarpophalangeal joints are often involved, producing a condition that resembles osteoarthritis but at a site typically affected by rheumatoid arthritis. Treatment of the arthritis is often disappointing, but identification of the underlying disease permits institution of life-saving phlebotomy therapy.     

Determination of aspirin and salicylic acid in transdermal perfusates

A high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of aspirin and salicylic acid in transdermal perfusates. The compounds were separated on a C8 Nucleosil column (5 microm, 250x4.6 mm) using a mobile phase containing a mixture of water-acetonitrile-orthophosphoric acid (650:350:2, v/v/v) and a flow-rate of 1 ml/min. The transdermal samples were in phosphate-buffered saline (PBS) and could be injected directly onto the HPLC system. The method was reproducible with inter-day R.S.D. values of no greater than 3.46 and 2.60% for aspirin and salicylic acid, respectively. The method was linear over the concentration range 0.2-5.0 microg/ml and had a limit of detection of 0.05 microg/ml for both compounds. For certain samples, it was necessary to ensure that no transmembrane leakage of the aspirin prodrugs had occurred. In these cases, a gradient was introduced by increasing the acetonitrile content of the mobile phase after the salicylic acid had eluted. The method has been applied to the determination of aspirin and salicylic acid in PBS following in vitro application of the compounds to mouse skin samples.     

HBeAg-negative hepatitis B in a previously thalassemic patient during immunosuppressive therapy for chronic GVHD

We report the case of a 15-year-old previously thalassemic girl who, 15 months after allogeneic BMT, developed HBeAg-negative hepatitis B (variant with mu-1896). In the absence of another route of transmission, HBV reactivation is postulated. The time of emergence of the HBV variant (with mu-1896) is probably related to the development of anti-HBe immunity. This mutant strain is associated with fulminant hepatitis. The patient achieved complete remission and HBV eradication despite having moderate GVHD and receiving immunosuppressive therapy.