[1H NMR study of the complexation of the quinolone antibiotic norfloxacin with DNA].

Complexation of antibiotic norfloxacin (NOR) with DNA fragments 5'-d(TpGpCpA) and 5'-d(CpGpCpG) has been studied in aqueous solution by 1H NMR spectroscopy (500 MHz). Equilibrium parameters of the complexation with single-stranded and duplex forms of DNA oligomer--equilibrium constants, enthalpy and entropy--have been obtained for the first time. Based on the analysis of the complexation parameters as well as induced chemical shifts of the antibiotic protons within different complexes, it was found that NOR binds with the tetramer duplexes mainly by intercalation. The complexation with the single-stranded form may occur either by intercalation and external binding. The site of preferential binding of the antibiotic with DNA duplex is GC site.

[A stochastic model for the NMR analysis of the heteroassociation of biologically active aromatic molecules]. / Stokhasticheskaia model' dlia IaMR-analiza geteroassotsiatsii biologicheski aktivnykh aromaticheskikh molekul.

A stochastic model for the NMR analysis of the heteroassociation of two aromatic compounds was developed, which takes into account all physically possible reactions of association of molecules in solution. Expressions for calculating the experimentally observed proton chemical shift were obtained in the general form, and an algorithm for calculating the parameters of heteroassociation using the stochastic model was proposed. The effects of limitations of the basic and general models, as compared with the stochastic model, on the model parameters of the heteroassociation of various biologically active aromatic molecules was analyzed. It was shown that the basic model can be used with a sufficient degree of accuracy for systems with a relatively small contribution of heteroassociation reactions to the total dynamic equilibrium in solution, whereas the general model describes satisfactorily the parameters of heteroassociation practically for all systems studied.

[Thermodynamic analysis of interaction of mitoxantrone with deoxytetranucleotide 5'-d(TpGpCpA) in the water solution based on 1H-NMR spectrophotometry]. / Termodinamicheskii analiz vzaimodeistviia antibiotika mitoksantrona s dezoksitetranukleotidom 5'-d(TpGpCpA) v vodnom rastvore po dannym 1H-IaMR-spektroskopii.

The complex formation of the antibiotic mitoxantrone (novantrone) with the deoxytetranucleotide 5'-d(TpGpCpA) in an aqueous salt solution was studied by one- and two-dimensional (2D-TOSCY and 2D-NOESY) 1H NMR spectroscopy (500 MHz). Concentration and temperature dependence of proton chemical shifts of molecules were measured. On the basis of these data, the equilibrium constants of the reaction, the relative content of various complexes as a function of concentration and temperature, the limiting values of chemical shifts of novantrone in complexes, and the thermodynamic parameters delta H and delta S of complex formation of molecules were calculated. It was concluded that the attachment sites for novantrone are pyrimidine-purine nucleotide sequences, sites d(TG) and d(CA) of the tetranucleotide duplex. The analysis of the thermodynamic parameters of the complex formation suggests that intermolecular hydrogen bonds and electrostatic interactions of the aminoalkyl chains of novantrone with the duplex d(TpGpCpA)2 play an important role in the stabilization of complexes 1:2 and 2:2. The results were compared with those obtained earlier for typical intercalators of ethidium bromide and daunomycin under identical experimental conditions.

Dysferlin protein analysis in limb-girdle muscular dystrophies.

Dysferlin is the protein product of the DYSF gene mapped at 2p31, which mutations cause limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy. To date, nine autosomal recessive forms (AR-LGMD) have been identified: four genes, which code for the sarcoglycan glycoproteins, are associated with both mild and severe forms, the sarcoglycanopathies (LGMD2C, 2D, 2E and 2F). The other five forms, usually causing a milder phenotype are LGMD2A (calpain 3), LGMD2B (dysferlin), LGMD2G (telethonin), LGMD2H (9q31-11), and LGMD21 (19q13.3). We studied dysferlin expression in a total of 176 patients, from 166 LGMD families: 12 LGMD2B patients, 70 with other known forms of muscular dystrophies (LGMD2A, sarcoglycanopathies, LGMD2G), in an attempt to assess the effect of the primary gene-product deficiency on dysferlin. In addition, 94 still unclassified LGMD families were screened for dysferlin deficiency. In eight LGMD2B patients from five families, no dysferlin was observed in muscle biopsies, both through immunofluorescence (IF) and Western blot methodologies, while in two families, a very faint band was detected. Both patterns, negative or very faint bands, were concordant in patients belonging to the same families, suggesting that dysferlin deficiency is specific to LGMD2B. Myoferlin, the newly identified homologue of dysferlin was studied for the first time in LGMD2B patients. Since no difference was observed between patients mildly and severely affected, this protein do not seem to modify the phenotype in the present dysferlin-deficient patients. Dystrophin, sarcoglycans, and telethonin were normal in all LGMD2B patients, while patients with sarcoglycanopathies (2C, 2D, and 2E), LGMD2A, LGMD2G, and DMD showed the presence of a normal dysferlin band by Western blot and a positive pattern on IF. These data suggest that there is no interaction between dysferlin and these proteins. However, calpain analysis showed a weaker band in four patients from two families with intra-familial concordance. Therefore, this secondary deficiency of calpain in LGMD2B families, may indicate an interaction between dysferlin and calpain in muscle. Dysferlin was also present in cultured myotubes, in chorionic villus, and in the skin. Dysferlin deficiency was found in 24 out of a total of 166 Brazilian AR-LGMD families screened for muscle proteins (approximately 14%), thus representing the second most frequent known LGMD form, after calpainopathy, in our population.

What's missing from multicultural competency research: review, introspection, and recommendations.

Much of the multicultural counseling research has pointed out the need for counselors to become culturally competent to appropriately address the needs of an emerging diverse community. To date, however, this body of research has largely focused on counselor competencies, with little attention being given to the client perspective of multicultural counseling competencies. This article discusses the importance of integrating the client perspective within the historical context of the multicultural literature by examining client preferences and expectations, as well as the adequacy of the current empirical data. The authors also raise the issue of politics inherent in multiculturalism and discuss how this affects the research. A number of recommendations are made as a guide for future research.

The development and initial validation of the Multicultural Environmental Inventory: a preliminary investigation.

This article describes the development and initial validation of the Multicultural Environmental Inventory (MEI). The MEI is an instrument designed to measure an individual's perceptions about the degree to which graduate counseling programs address multicultural issues within curriculum, supervision, climate, and research. This investigation was conducted using the data from 208 students and faculty from counseling psychology graduate programs across the United States approved by the American Psychological Association. By using techniques of exploratory factor analysis, a 4-factor solution was determined to account for the relationships among the items on the MEI. The instrument was modified from 53 to 27 items on the basis of the items' effectiveness in measuring the underlying constructs of interest, and internal consistency information is provided on the final revised instrument (MEI-R). The factors underlying the MEI-R are discussed within the context of a multicultural environment in graduate counseling programs, and directions for future research are considered.

Myoferlin, a candidate gene and potential modifier of muscular dystrophy.

Dysferlin, the gene product of the limb girdle muscular dystrophy (LGMD) 2B locus, encodes a membrane-associated protein with homology to Caenorhabditis elegans fer-1. Humans with mutations in dysferlin ( DYSF ) develop muscle weakness that affects both proximal and distal muscles. Strikingly, the phenotype in LGMD 2B patients is highly variable, but the type of mutation in DYSF cannot explain this phenotypic variability. Through electronic database searching, we identified a protein highly homologous to dysferlin that we have named myoferlin. Myoferlin mRNA was highly expressed in cardiac muscle and to a lesser degree in skeletal muscle. However, antibodies raised to myoferlin showed abundant expression of myoferlin in both cardiac and skeletal muscle. Within the cell, myoferlin was associated with the plasma membrane but, unlike dysferlin, myoferlin was also associated with the nuclear membrane. Ferlin family members contain C2 domains, and these domains play a role in calcium-mediated membrane fusion events. To investigate this, we studied the expression of myoferlin in the mdx mouse, which lacks dystrophin and whose muscles undergo repeated rounds of degeneration and regeneration. We found upregulation of myoferlin at the membrane in mdx skeletal muscle. Thus, myoferlin ( MYOF ) is a candidate gene for muscular dystrophy and cardiomyopathy, or possibly a modifier of the muscular dystrophy phenotype.

Home care for the urban chronically ill elderly in the People's Republic of China.

This study examines the home care situation of seventy-five urban chronically ill men and women and their caregivers in three cities in the People's Republic of China. It documents the type of home care provided, the severity of illness, and the dependency in activities of daily living in order to appreciate the complexity of these care situations. The findings reveal that women serve as the caregivers in the majority of the cases and often they are elderly spouses with health problems of their own. The physical, social, psychological, and financial problems experienced by these patients create an enormous burden for the caregivers whether spouses or younger family members coming home from work to a second shift. If alternatives to home care, such as nursing homes, were available, 54 percent of these caregivers would be willing to institutionalize their elderly relative. All caregivers express the need for more assistance in providing home care. This study raises questions regarding the role of the family, the state, and specifically the health care system in caring for the elderly chronically ill in light of their increasing numbers in the population.

Efficacy and complication rate of 16,224 consecutive peribulbar blocks. A prospective multicenter study.

Although usually safe, retrobulbar anesthesia and peribulbar anesthesia have potentially sight- and life-threatening complications. Although it has been suggested that peribulbar anesthesia is as effective and safer than retrobulbar anesthesia, no large study has addressed the true rate of complications. To determine the efficacy and safety of peribulbar anesthesia, this study prospectively examined 16,224 consecutive peribulbar blocks. Twelve centers in the United States, Germany, and Chile participated in the study. After a peribulbar block was administered, the degree of akinesia, amaurosis, percentage of supplemental blocks required, and side effects and complications occurring after the block and for six weeks were recorded. Perioperative and late optic nerve complications were included. To approximate a real-life situation, ophthalmologists, anesthesiologists, and certified registered nurse anesthetists performed the blocks. Ninety-five percent of patients achieved a 95% or greater degree of akinesia. The incidence of complications in the consecutive cases was low. Orbital hemorrhage occurred in 12 cases (0.74%). There was one globe perforation (0.006%), two expulsive hemorrhages (0.013%), one grand mal seizure (0.006%), and no cases of cardiac or respiratory depression or deaths. Peribulbar is as effective as retrobulbar anesthesia and appears to lead to fewer sight- and life-threatening complications, even when slightly different peribulbar techniques are used. This is especially true when the anesthetic is administered with a 1 1/4-inch or shorter needle with the eye in the primary position, followed by ten to 15 minutes of ocular compression.

Exploring multicultural competencies of occupational therapists: implications for education and training.

The purpose of this investigation was to explore the influence of demographic and educational variables on self-reported multicultural competencies of occupational therapists. A sample of 94 occupational therapists currently working in the field participated in this investigation. Multicultural course work, seminars and workshops, percentage of minority patients worked with, and highest degree held were found to correlate significantly with self-reported multicultural competencies. Regression analyses found that highest degree held, percentage of minority patients worked with, multicultural course work, and participation in multicultural seminars and workshops accounted for about half of the variance in multicultural awareness. These findings are discussed in terms of academic courses and continued professional training and education for occupational therapists.

Posterior peribulbar anesthesia: an alternative to retrobulbar anesthesia.

Peribulbar anesthesia is a safe alternative to retrobulbar anesthesia for ophthalmic surgery. Because the anesthetic is deposited outside the muscle cone, the potential for intraocular or intradural injection is greatly minimized. Furthermore, intraconal hemorrhage and direct optic nerve injury is avoided. We illustrate the details of our technique for posterior peribulbar anesthesia and describe our experience in over 3,000 cases.