MN blood-group locus: data concerning the possible chromosomal location.

Combined data derived from clinical, cytogenetic, and blood-grouping studies of one family suggest that the MN locus is on the long arm of either the No. 2 or the No. 4 chromosome.

The HLA system in congenital rubella patients with and without diabetes.

The HLA antigens of 173 patients with the congenital rubella syndrome (CR) are reported. Twenty-one of these patients are also clinically diabetic, and among them the frequencies of the HLA antigens DR2 and DR3 are significantly lower and higher, respectively, than in CR patients without diabetes or in controls. These data suggest that the genes that control susceptibility to type I or insulin-dependent diabetes mellitus are necessary for the development of glucose intolerance in CR patients.

Health and well-being of childbearing women in rural and urban contexts.

As part of the national focus on women's health issues, it is important to identify those health-related characteristics of rural women that distinguish them from women living in urban settings. The aim of this study was to compare rural and urban childbearing women on socioeconomic characteristics, perceived stress, health-related practices, illness symptoms, parenting confidence, and body weight. One hundred sixty-five midwestern women responded to a health survey sent to them six months after childbirth. Rural women were younger and less educationally and economically advantaged compared to urban women. Before adjusting for these differences, rural women were less self-actualized, more interpersonally isolated, and reported less healthy nutrition than urban women. These differences disappeared when socioeconomic differences were adjusted. Rural and urban mothers did not differ in most other areas, including perceived stress, parenting confidence, and body weight. Compared to national norms, the perceived stress levels of both rural and urban mothers were significantly higher than a probability sample of U.S. women. Findings support the role of socioeconomic factors as contributing to risk of poor health promotion among rural childbearing women.

Intratracheal aerosolization of endotoxin in the rat: a model of the adult respiratory distress syndrome (ARDS).

A technique is described for the intratracheal aerosolization of endotoxin into the rat. Using a miniaturized nozzle within the tracheal lumen to optimize uniform distribution 0.5 ml of an endotoxin solution (7 mg/kg) was aerosolized and dispersed throughout the lung. Time course studies of pulmonary function and histological changes revealed marked functional and morphological changes by 24 h. Histopathologic changes consisted of widespread pulmonary oedema and a diffuse neutrophilic alveolitis. At the same time, there were significant decreases in tidal volume, minute ventilation and lung compliance. Haematologic changes were also seen, including profound thrombocytopaenia and leukopaenia together with an increased haematocrit, indicating systemic effects in this model. Bronchoalveolar lavage (BAL) at 24 h revealed significant increases in BAL protein, erythrocytes and neutrophils. The functional, cytological and histological changes observed after endotoxin challenge mimic those seen in the Adult Respiratory Distress Syndrome in humans and can thus be used as a model to compare the efficacy of a variety of therapeutic interventions for this syndrome.

Designing the smaller library: a hospital looks to the future.

Like other libraries, hospital libraries are preparing for a future which will include a mix, as yet undetermined, of print and electronic information. This case study relates how the library at St. Jude Children's Research Hospital was designed to meet the needs of users and staff and to balance them with the need for more sophisticated methods of retrieving, storing, and delivering information. Details are provided on planning process and on design features such as lighting and color.

Range highlight facility within region of interest for air-CT cisternography and canalography.

Air-CT cisternography and canalography have improved the radiographic diagnosis of small acoustic neuromas. Institutions that do not have an Independent Viewing System with their CT unit can improve their technique by data manipulation using the Range Highlight Facility within the Region of Interest as a part of their existing commercial unit.

Desmoplastic melanoma: a 12-year experience with sentinel lymph node biopsy.

AIMS: Given the paucity of data regarding nodal involvement in desmoplastic melanoma (DM), we decided to review the incidence of nodal metastasis in our patients with DM to better define guidelines regarding the performance of sentinel lymph node biopsy (SLNB) in this specific melanoma subtype. METHODS: Using a prospectively maintained database, we reviewed all patients who underwent treatment for melanoma at the Yale Melanoma Unit in a twelve-year period (1998-2010), during which 3531 cases were treated. We identified 24 patients (0.7%) diagnosed with DM. These patients' records were studied for clinical and histologic parameters and clinical outcomes. RESULTS: Twenty-two patients from the DM group had SLNB, of which four (18%) were diagnosed with micro-metastasis. These four patients were all treated with completion lymphadenectomy and none had additional positive nodes in the remainder of the nodes. Patients were followed after surgery for a median of 25 months (range 2-60 months). Two patients (9%) developed local recurrence, two (9%) in-transit recurrence, and six (27%) showed distant metastases (three patients were pure DM and three patients showed mixed morphology). Patients with mixed DM had a higher rate of nodal metastasis (25%) vs those with pure DM (14%). CONCLUSIONS: Other authors have reported that patients diagnosed with pure DM were less likely to have a positive SLN (0-2%) than those patients with the mixed DM subtype (12-16%). Our findings of higher incidence rates of regional lymph node metastases in both the pure and mixed DM subtypes (14% and 25%) compel us to continue to still recommend that SLNB be considered in patients with both subcategories, pure and mixed DM. LEVEL OF EVIDENCE: Level IV.

Influence of radioactivity on surface interaction forces.

Although some differences have been observed, the transport behavior of radioactive aerosol particles has often been assumed to be analogous to the behavior of nonradioactive aerosols in dispersion models. However, radioactive particles can become electrostatically charged as a result of the decay process. Theories have been proposed to describe this self-charging phenomenon, which may have a significant effect on how these particles interact with one another and with charged surfaces in the environment. In this study, atomic force microscopy (AFM) was employed to quantify surface forces between a particle and a planar surface and to compare measurements with and without the involvement of radioactivity. The main objective of this work is to assess directly the effects of radioactivity on the surface interactions of radioactive aerosols via the measurement of the adhesion force. The adhesion force between a silicon nitride AFM tip and an activated gold substrate was measured so that any possible effects due to radioactivity could be observed. The adhesion force between the tip and the gold surface increased significantly when the gold substrate (25 mm(2) surface area) was activated to a level of approximately 0.6 mCi. The results of this investigation will prompt further work into the effects of radioactivity in particle-surface interactions.

International collaboration between US and Thailand on a clinical trial of treatment for HIV-associated cryptococcal meningitis.

BACKGROUND: International clinical trials can provide scientific and logistic benefits in spite of the many challenges. Determining whether a country, especially a developing country, is an appropriate location for the research should include in-country consultation and partnering to assess its social value for the population; that treatments are relevant for the population under study; and that the research infrastructure and ethical oversight are adequate. Collaboration increases the likelihood of study success and helps ensure that benefits accrue to recruited populations and their community. PURPOSE: This paper describes our experiences on a bi-national study and may provide guidance for those planning to engage in future collaborations. METHODS: A Thai and United States team collaborated to develop and implement a phase II clinical trial for HIV-associated cryptococcal meningitis to assess safety and tolerability of combination therapy vs. standard treatment. Clinical and cultural differences, regulatory hurdles and operational issues were addressed before and during the study to ensure a successful collaboration between the 2 groups. RESULTS: The international multicenter study allowed for more rapid enrollment, reduced costs to complete the study, sharing of the benefits of research, greater generalizability of results and capacity building in Thailand; quality metrics in Thailand were equivalent to or better than those in the U.S. CONCLUSIONS: Conducting successful clinical trials internationally requires early and ongoing collaboration to ensure the study meets sites' requirements and expectations, conforms to varying national regulations, adheres to data quality standards and is responsive to the health needs of studied populations.

A new hospital library: a marketing opportunity.

A new or remodeled library presents a unique marketing opportunity for the hospital librarian. Furthermore, a well-designed library markets itself through its convenience, attractiveness, and ease of use. A marketing approach to library planning takes into account needs of users and of library staff and considers the librarian's relations with the architect as well as with hospital employees. This paper describes ways to combine library planning with marketing techniques and specifies aspects of the library that contribute to its good image.

An analysis of auditory alphabet confusions.

The present study, using the nonhierarchical overlapping clustering algorithm MAPCLUS to fit the Shepard-Arabie (1979) ADCLUS model, attempted to derive a set of features that would accurately describe the auditory alphabet confusions present in the data matrices of Conrad (1964) and Hull (1973). Separate nine-cluster solutions accounted for 80% and 89% of the variance in the matrices, respectively. The clusters revealed that the most frequently confused letter names contained common vowels and phonetically similar consonants. Further analyses using INDCLUS, an individual differences extension of the MAPCLUS algorithm and ADCLUS model, indicated that while the patterns of errors in the two matrices were remarkably similar, some differences were also apparent. These differences reflected the differing amounts of background noise present in the two studies.

Isolation of a yeast mutant deficient in pyruvate carboxylase activity.

To improve our understanding of the catalytic mechanism and regulatory properties of pyruvate carboxylase (EC 6.4.1.1), an important biotin-dependent enzyme, we have sought to isolate mutants in Saccharomyces cerevisiae which are defective in pyruvate carboxylase activity. One mutant was isolated which was unable to grow on glucose minimal medium unless supplemented with aspartate. Although the enzyme had only 25% of the wild type pyruvate carboxylase activity, Western analysis and RNase protection analysis demonstrated that the mutant gene was expressed at approximately 70% of the wild type level. On the basis of genetic crosses and complementation tests, we have attributed the defect to mutations in the PYC gene encoding pyruvate carboxylase.

When children die: death in current children's literature and its use in a library.

Death and dying are dealt with realistically and sympathetically in current children's literature. Books can play an important role in helping children suffering from catastrophic illness by showing how other children have coped with similar situations; they can also form a basis for bibliotherapy with patients. This paper examines current trends in children's literature and describes how these books have been incorporated into a patient library at St. Jude Children's Research Hospital.

Transport of the yeast ATP synthase beta-subunit into mitochondria. Effects of amino acid substitutions on targeting.

We have isolated the yeast ATP2 gene encoding the beta-subunit of mitochondrial ATP synthase and determined its nucleotide sequence. A fusion between the N-terminal 15 amino acid residues of beta-subunit and the mouse cytosolic protein dihydrofolate reductase (DHFR) was transcribed and translated in vitro and found to be transported into isolated yeast mitochondria. A fusion with the first 35 amino acid residues of beta-subunit attached to DHFR was not only transported but also proteolytically processed by a mitochondrial protease. Amino acid substitutions were introduced into the N-terminal presequence of the beta-subunit by bisulphite mutagenesis of the corresponding DNA. The effects of these mutations on mitochondrial targeting were assessed by transport experiments in vitro using DHFR fusion proteins. All of the mutants, harbourin from one to six amino acid substitutions in the first 14 residues of the presequence, were transported into mitochondria, though at least one of them (I8) was transported and proteolytically processed at a much reduced rate. The I8 mutant beta-subunit also exhibited poor transport and processing in vivo, and expression of this mutant polypeptide failed to complement the glycerol- phenotype of a yeast ATP2 mutant. More remarkably, the expression of I8 beta-subunit induced a more general growth defect in yeast, possibly due to interference with the transport of other, essential, mitochondrial proteins.

Identification of novel alternatively spliced pyruvate carboxylase mRNAs with divergent 5'-untranslated regions which are expressed in a tissue-specific manner.

We have identified and characterized multiple mRNA transcripts of rat and human pyruvate carboxylases [EC 6.4.1.1] using rapid amplification of cDNA 5' ends-polymerase chain reaction (RACE-PCR). Five alternative forms of rat pyruvate carboxylase cDNAs have been identified in liver, kidney, brain, and adipose tissue and these are expressed in a tissue-specific manner. Two alternative forms of human pyruvate carboxylase cDNA have also been identified in liver. These pyruvate carboxylase cDNAs have a common coding region but differ in their 5' untranslated regions (5'UTRs), suggesting that they are generated by alternative splicing of the primary transcript. Southern blot analysis of restriction enzyme digested rat genomic DNA revealed that pyruvate carboxylase is encoded by a single copy gene.

Biochemical genetics of MN.

Quantitative hemagglutination studies of the MN-hemizygous (M/-) patient and his family reported by German et al. are given together with data on the electrophoretic mobility of their red cells. These results, and those obtained on the cells of a donor of the MU phenotype (MU=M+N-S-s-U+); Mu=M+N-S-s-U), demonstrate a series of shortcomings in the current 'precursor transferase' theory of the biochemical genetics of MN antigens. Another theory is proposed, according to which the effects of the MN genes take place exclusively in the protein part of the glycopeptide. The MN proteins would carry acceptor sites for the antigenic oligosaccharides which are put together by enzymes genetically independent of MN. In M glycoproteins, the acceptor sites are close to each other, in doublets, while in N they are all separate. This model is shown to apply successfully to several difficult problems in MN.

Epilepsy and oral contraception.

A controlled cross-over trial in 20 epileptic women, receiving regular anticonvulsant therapy showed that an oral contraceptive with a low oestrogen/ progestogen content had no significant effect on the average frequency of fits compared with identical dummy tablets.

Functional expression, purification, and characterization of recombinant human pyruvate carboxylase.

The cDNA-encoding human pyruvate carboxylase (hPC) has been assembled and cloned into a very high efficiency mammalian expression vector and the construct transfected into 293T kidney cells. Stable clones expressing very high levels of hPC were produced and used as a source of the enzyme. Purification of the recombinant hPC was performed by selective precipitation with 40% ammonium sulfate followed by a single step avidin affinity chromatography, with an overall yield of 20%. Recombinant hPC purified by this method yielded a single band on SDS-PAGE with a specific activity of 20 U/mg. Kinetic analysis demonstrated that the recombinant human PC has the same properties as the native enzyme isolated from liver autopsy. This is the first report of production and purification of recombinant PC.