Restructuring care. Danbury Health System realigns structures to improve care while preparing for risk-bearing demands.
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Case Management↗
Biomedical subjects
M Miller
Publications and source records attributed to M Miller.
Screening Childhood Cancer Survivors for Breast Cancer.
The development of second primary solid tumors, especially breast neoplasms, is increased among patients who have survived childhood or adolescent malignancies. With the increased long-term survival of patients with pediatric cancer, questions regarding breast cancer screening in this group have been raised. At this time, there are no established guidelines for breast cancer surveillance in this high-risk population. The objective of this review is to summarize the incidence, list additional risk factors for the development of breast cancer, and discuss the benefits of early detection of second primary breast cancers in pediatric cancer survivors. We have devised an algorithm for breast cancer screening in survivors of childhood malignancy. Implications of treatment with radiation and chemotherapy and the influence on prognosis of genetic abnormalities such as p53 mutations are debated.
Journal Article↗
Mutations within the yeast U4/U6 snRNP protein Prp4 affect a late stage of spliceosome assembly.
We showed previously that the yeast Prp4 protein is a spliceosomal factor that is tightly associated with the U4, U5, and U6 small nuclear RNAs. Moreover, Prp4 appears to associate very transiently with the spliceosome before the U4 snRNA dissociates from the spliceosome. Prp4 belongs to the Gbeta-like protein family, which suggests that the Prp4 Gbeta motifs could mediate interactions with other components of the spliceosome. To investigate the function of the Gbeta motifs, we introduced mutations within the second WD-repeat of Prp4. Among the 35 new alleles found, 24 were pseudo wild-type mutants, 8 failed to grow at any temperature, and 3 were conditional sensitive mutants. The biochemical defects of the three thermosensitive prp4 mutants have been examined by immunoprecipitation, native gel electrophoresis, and glycerol gradient centrifugation. First, we show that snRNP formation is not impaired in these mutants and that Prp4 is present in the U4/U6 and U4/U6-U5 snRNP particles. We also demonstrate that spliceosome assembly is largely unaffected despite the fact that the first step of splicing does not occur. However, both Prp4 and U4 snRNA remain tightly associated with the spliceosome and this blocks the transition toward an active form of the spliceosome. Our results suggest a possible role of Prp4 in mediating important conformational rearrangements of proteins within the spliceosome that involve the region containing the Gbeta-repeats.
Amino Acid Sequence↗
Predictors and profiles of rural versus urban family practice.
BACKGROUND AND OBJECTIVES: Much of rural Colorado has been designated a shortage area for primary care health personnel. The state's only medical school and its family practice residency programs are expected to address this long-standing problem. This study identified predictors of rural practice location and contrasted the service profiles of rural versus urban family physicians and general practitioners. METHODS: The Colorado Board of Medical Examiners mailed a questionnaire to all licensed Colorado physicians. Logistic regression analyses were conducted using variables determined to be significantly related to practice location (rural versus urban) by univariate statistical tests. Information from the 986 family physician and general practitioner respondents identified personal and educational variables strongly associated with choice of rural practice location and differentiated between practice tendencies of rural versus urban physicians. RESULTS: Having been raised in rural Colorado was the most powerful predictor of rural practice location in the state. Family physicians and general practitioners serving rural populations spent much more time weekly providing direct patient care and more often cared for Medicaid patients. CONCLUSIONS: Personal characteristics and background may be useful considerations in selecting among applicants for medical schools and family practice residency programs committed to reducing the severe shortage of health care service in rural areas.
Adult↗
Analysis of the structure of HIV-1 protease complexed with a hexapeptide inhibitor. Part II: Molecular dynamic studies of the active site region.
Six models of the catalytic site of HIV-1 protease complexed with a reduced peptide inhibitor, MVT-101, were investigated. These studies focused on the details of protonation of the active site, its total net charge and hydrogen bonding pattern, which was consistent with both the observed coplanar configuration of the acidic groups of the catalytic aspartates (Asp-25 and Asp-125) and the observed binding mode of the inhibitor. Molecular dynamic simulations using AMBER 4.0 indicated that the active site should be neutral. The planarity of the aspartate dyad may be due to the formation of two hydrogen bonds: one between the inner O delta 1 oxygen atoms of the two catalytic aspartates and another between the O delta 2 atom of Asp-125 and the nitrogen atom of the reduced peptide bond of the bound inhibitor. This would require two additional protonations, either of both aspartates, or of one Asp and the amido nitrogen atom of Nle-204. Our results favor the Asp-inhibitor protonation but the other one is not excluded. Implications of these findings for the mechanism of enzymatic catalysis are discussed. Dynamic properties of the hydrogen bond network in the active site and an analysis of the interaction energy between the inhibitor and the protease are presented.
Binding Sites↗
Public health impact on drug residues in animal tissues.
Consumers have expressed concern regarding the health impact of drug residues in their food. Animal residues in animal tissues above the legal tolerance clearly have an impact on human health. Tolerances represent the maximal level or concentration of antimicrobial residues permitted in animal tissues at the time of slaughter. The tolerances are intended to ensure that residual drugs will have no harmful effects if ingested. This paper describes the existing evidence for specific health hazards for certain pharmacological classes of drugs and explains the risks associated with drug residues in meat and poultry above the established tolerance. The primary focus is on possible public health consequences that may occur as a result of acute exposure to illegal residues. In addition, long-term effects are discussed with added comments about the effect of residues on the intestinal flora. Most residues of veterinary drugs occur in food at such low levels that they rarely pose a chronic or long-term health hazard to consumers. The importance of food safety through the reduction of residues in our food supply cannot be overemphasized. Food safety remains a major challenge confronting contemporary society.
Animals↗
Inappropriate antidiuretic hormone secretion.
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Acute Disease↗
[Pulmonary mycobacteriosis--diagnostic problem and prevalence in Poland (a retrospective study)].
The diagnosis of pulmonary mycobacteriosis was verified in 267 patients in Poland, classified in the years 1991-1995 to group VI M. Among 267 patients, 213 were men in age 28-83 years (median 43 years) and 54 women in age 24-81 years (median 50 years). The verification of the diagnosis was based on the authors own criteria of pulmonary mycobacteriosis and colonisation. These criteria included at least two positive sputum cultures and presence or absence of the respiratory tract inflammation. Pulmonary mycobacteriosis was recognised in 199 patients (168 men and 31 women). Colonisation was diagnosed in 41 patients (23 men and 18 women). Non-tuberculous mycobacteria most often responsible for pulmonary mycobacteriosis were identified as M. kansasii, M. avium--intracellulare and M. xenopi. Majority of patients with pulmonary mycobacteriosis or with colonisation had pulmonary lesions caused by tuberculosis in the past or suffered from chronic obstructive pulmonary disease. In 63 cases, data concerning previous diseases of the respiratory tract were not available.
Adult↗
Patients with troublesome sweating.
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Diethylstilbestrol↗
Educating rural allied health professionals: an interdisciplinary effort.
This article describes the process and outcome of an innovative, interdisciplinary educational effort which was initiated in rural Maine. Within the context of a comprehensive, statewide interdisciplinary rural health care training project that was federally funded through the Interdisciplinary Training for Health Care for Rural Areas (ITHCRA) grant program, a primary strategy for recruiting and training rural allied health practitioners was the development and implementation of a year long interdisciplinary graduate course sequence. The results of the evaluation suggested that interdisciplinary education is not only useful in learning the roles and functions of allied health professions, but is valuable tool in promoting the development of skills necessary for competent and relevant rural allied health practice.
Allied Health Personnel↗
[Reasons for chronic expectoration in patients with pulmonary tuberculosis registered in the Central Tuberculosis Registry].
The aim of the retrospective population-based study was to identify reasons for failure of sputum culture negativity from the 12th month on since the start of chemotherapy of pulmonary tuberculosis (PTB). Medical records of 97 patients with PTB (85 men and 12 women) remaining sputum culture positive for over 12 months, reported to the Central TB Registry (1988-1990), were reviewed. The mean age was 46.7 years. There were 39.2% blue collar workers, 18.6% peasants, 21.6% unemployed, 14.4% pensioners. Only 4.1% constituted persons with education above elementary level. 44 patients abused alcohol, 13 of them had severe alcohol related health problems. Initial susceptibility tests were done in 79 subjects, showing resistance to at least one drug in 15. In 21 subjects the new resistance occurred during observation. The mean period until conversion of sputum culture was 23.5 months. Sputum culture conversion was finally achieved in 63 (64.9%) subjects. The reasons for delayed sputum culture conversion were identified in 86 persons. The main reason for long duration of positive sputum culture in 75 (87.2%) subjects was poor compliance. In 7 (8.1%) cases evident treatment error was relevant. Serious adverse reactions to drugs were responsible in 4 (4.6%).
Adult↗
[Epidemiology of tuberculosis in Poland and in the world].
The paper describes the risk of tuberculosis infection and the incidence of the disease as measures of the epidemiological situation and presents data on the epidemiological situation of tuberculosis in Poland and the world. It also describes the effectiveness of the national tuberculosis control programme in Poland. The annual risk of tuberculosis infection in Poland is estimated at 0.2% which is about 10 times higher than the lowest one in Europe (the Netherland), but there are countries in the world with the risk of 2.0% and higher. The incidence of tuberculosis in Poland (all forms) declined from 182.6/100,000 in 1965 to less than 40,0/100,000 in 1996, of which less than half were bacteriologically positive cases. The incidence of smear positive cases, the most infectious group, declined from 18.7/100,000 in 1980 to 9.7/100,000 in 1995. All cases of tuberculosis in Poland are treated with 4-drugs regimen in the intensive phase of treatment and 3-drugs in the continuation phase. The duration of treatment is 6-8 months and the cure rate is above 90%.
Adolescent↗
Transient neonatal arthrogryposis: another case.
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Arthrogryposis↗
Posttransplant lymphoproliferative disease after cardiac transplantation. Two unusual variants with predominantly plasmacytoid features.
Two patients who developed posttransplant lymphoproliferative disorder with plasmacytoid changes in the lymphocytes after heart transplant are described. The first case is one of multiple myeloma, and the second is a case of lymphoma with plasmacytoid features. The clinical course and the etiologic role of the immunosuppressive therapies that the patients received for heart transplantation are described. A review of posttransplant multiple myeloma and discussion of the etiology and prognosis of this entity are presented.
Heart Transplantation↗
Modulation of membrane currents and mechanical activity by niflumic acid in rat vascular smooth muscle.
The effects of niflumic acid on whole-cell membrane currents and mechanical activity were examined in the rat portal vein. In freshly dispersed portal vein cells clamped at -60 mV in caesium (Cs+)-containing solutions, niflumic acid (1-100 microM) inhibited calcium (Ca2+)-activated chloride currents (IC1(Ca)) induced by caffeine (10 mM) and by noradrenaline (10 microM). In a potassium (K+)-containing solution and at a holding potential of - 10 mV, niflumic acid (10-100 microM) induced an outward K+ current (IK(ATP)) which was sensitive to glibenclamide (10-30 microM). At concentrations < 30 microM and at a holding potential of -2 mV, niflumic acid had no effect on the magnitude of the caffeine- or noradrenaline-stimulated current (IBK(Ca)) carried by the large conductance, Ca(2+)-sensitive K+ channel (BKCa). However, at a concentration of 100 microM, niflumic acid significantly inhibited IBK(Ca)) evoked by caffeine (10 mM) but not by NS1619 (1-(2'-hydroxy-5'-trifluoromethylphenyl)-5-trifluoromethyl-2(3 H) benzimidazolone; 20 microM). In Cs(+)-containing solutions, niflumic acid (10-100 microM) did not inhibit voltage-sensitive Ca2+ currents. In intact portal veins, niflumic acid (1-300 microM) inhibited spontaneous mechanical activity, an action which was partially antagonised by glibenclamide (1-10 microM), and contractions produced by noradrenaline (10 microM), an effect which was glibenclamide-insensitive. It is concluded that inhibition of ICl(Ca) and stimulation of IK(ATP) both contribute to the mechano-inhibitory actions of niflumic acid in the rat portal vein.
Adrenergic alpha-Agonists↗
The oligomerization domain of p53: crystal structure of the trigonal form.
The structure of the oligomerization domain of the p53 tumor suppressor protein was determined in the trigonal crystal form, using a refined NMR structure as a model. A synthetic peptide comprising residues 319-360 of human p53 crystallized in the space group P3(1)21. There is one biologically relevant tetrameric domain in the crystallographic asymmetric unit. The structure was refined jointly with NMR data, only the third such case (the previous examples being IL-1beta (Shaanan, B., Gronenborn, A.M., Cohen, G.H., Gilliland, G.L., Veerapandian, B., Davies, D.R. and Clore, G.M. (1992) Science 257, 961-964 [1]) and BPTI (Schiffer, C., Huber, R., Wuthrich, K. and Van Gunsteren, W.F. (1994) J. Mol. Biol. 241, 588-599 [21)), to 2.5 A resolution with an R factor of 0.207. The distribution of tumor-derived mutations in the oligomerization region together with structural and biological data suggest a strategy for the design of antitumor therapeutics.
Biopolymers↗
Fluoro-Green and Fluoro-Red: two new fluorescent retrograde tracers with a number of unique properties.
As a means of improving nerve tract-tracing in the peripheral and central nervous systems we experimented with two (retrograde) fluorescent emulsions, which we have tentatively named Fluoro-Green (FGr) and Fluoro-Red (FRe), and which we believe possess the following seven advantages: (1) they show little diffusion beyond the injection site; (2) their excitation/emission characteristics allow their use in double-tracing experiments; (3) they do not 'leak' from labeled cells; (4) their fluorescence is presented as large granules in the cytoplasm and its processes; (5) the fluorescence lasts for a sufficiently long time to permit repeated observation; (6) they may be used in combination with a wide variety of other neuroanatomical tracing methods; (7) they are economical, non-toxic and easy to utilize.
Animals↗
Highly ordered two-dimensional crystals of photosystem I reaction center from Synechococcus sp.: functional and structural analyses.
The photosystem 1 reaction center complex from the thermophilic cyanobacterium Synechococcus sp. was isolated by Triton X-100 solubilization and fractional precipitation with polyethylene glycol. As shown by gel electrophoresis, the isolated complex was composed of the 83 kDa subunits A and B, and at least six other subunits with molecular mass below 20 kDa. Electron transfer from the primary electron donor P700 to the FA/FB centers was demonstrated by flash-induced absorption change of the isolated complex, while electron paramagnetic resonance (EPR) spectroscopy showed that the complex contained a full set of Fe-S clusters. Isolated complexes were reconstituted into two-dimensional crystals in the presence of phospholipids and different cations. The crystals were found to be active by flash-induced separation and EPR spectroscopy. Electron microscopy and digital image processing of negatively stained and frozen-hydrated specimens revealed orthorhombic crystals with unit cell dimensions a = 138 A, b = 145 A and p12(1) symmetry. A three-dimensional map was calculated for negatively stained crystals to 19 A resolution, whereas the projection map of frozen-hydrated crystals exhibited 8 A resolution.
Crystallization↗