Changes needed in adult foster care.
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Aged↗
Biomedical subjects
L Miller
Publications and source records attributed to L Miller.
Careful research of psychedelics resumes.
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Brain↗
Construction of an ordered genomic library of Mycoplasma genitalium.
As a first step towards sequencing the chromosome of the suspected human pathogen Mycoplasma genitalium, we attempted to clone its entire genome in a set of ordered cosmids. Cosmid libraries were established by partial digestion of M. genitalium genomic DNA with Sau3AI or EcoRI. A chromosome-walking strategy was used to identify 20 overlapping cosmid clones which contained over 99% of the genome. The final 5.1 kb could not be cloned in cosmids, and was eventually obtained from a genomic library established in a lambda vector. Correspondence of cloned and genomic EcoRI fragments indicated no detectable major deletions or rearrangements in the library. The library was oriented on established XhoI and SmaI physical maps of the chromosome with restriction sites present at the expected locations in the library. The genome contained 74 EcoRI fragments which added up to a total genome size of 578 kb. These were arranged in a partial EcoRI physical map, and those containing the MgPa major attachment protein-encoding operon and its repeat sequences were identified. The existence of this ordered genomic library, which accurately and completely encompasses the entire M. genitalium genome, should serve as a valuable tool for many future studies of this organism and facilitate our long-term goal of sequencing its genome.
Bacterial Proteins↗
The cDNAs encoding two forms of the LYN protein tyrosine kinase are expressed in rat mast cells and human myeloid cells.
Two isoforms of lck/yes-related novel (LYN) protein tyrosine kinase (PTK) appear to play a role in B-cell-IgM and FcERI receptor signaling. The cDNAs lynA and lynB encoding these two forms were isolated and sequenced; they were derived from rat mucosal mast cell and human myeloid cell lines. The nucleotide (nt) and deduced amino acid (aa) sequences share 94 and 97% identity between rat and mouse lyn, respectively, and 88 and 96% identity between rat and human lyn. In all three species, a region of 20 aa is uniformly inserted at an identical site and its sequence is highly conserved. This suggests an important regulatory role for this region mediated by this PTK.
Amino Acid Sequence↗
Upregulation of AP-2 in the skin of Xenopus laevis during thyroid hormone-induced metamorphosis.
During amphibian metamorphosis dramatic changes occur in the morphogenesis and differentiation of the epidermis. Concurrently with these changes, the 63 kDa keratin gene is upregulated from low basal levels to high levels. What makes these processes unique is that they are controlled by triiodothyronine (T3) and can be duplicated in cultures of purified epidermal cells. Since there is a 2 day lag period between the addition of T3 and the upregulation of keratin gene expression and terminal differentiation, recent studies have focused on identifying the genes activated during the lag period. We assume that the transcription factors required for upregulation of the keratin gene are induced by T3 during the lag period, and therefore we have cloned the keratin gene so that promoter analyses can be conducted. S1 mapping assays have shown that the same transcription start sites are used during premetamorphosis when the keratin gene is basally expressed, during metamorphosis when it is T3-upregulated, and in the adult epidermis where it is expressed independently of T3. During the early part of the lag period TR beta and AP-2 mRNA levels are upregulated in the epidermis by T3. The transcription factor AP-2 is expressed at high levels in the skin of premetamorphic larvae and induced about fivefold by T3 but is not induced in an epithelial cell line (XL-177). Since the keratin mRNA, AP-2 mRNA, and other genes induced during the lag period are expressed in premetamorphic larvae it appears that T3 functions by upregulating the expression of genes previously activated by a T3-independent process. This preprogramming may account for the tissue specificity of T3 action during metamorphosis.
Animals↗
Molecular characterization of a plasmid-borne (pGT633) erythromycin resistance determinant (ermGT) from Lactobacillus reuteri 100-63.
Lactobacillus reuteri 100-63 contains a 9.8 kb plasmid (pGT633) encoding resistance to the macrolide-lincosamide-streptogramin (MLS) type B antibiotics. The restriction endonucleases AccI, BamHI, BclI, EcoRI, EcoRV, HhaI, HindII, HpaI, KpnI, SalI, and SspI were employed to establish a physical map of pGT633. Next, genetic transfer experiments were conducted to establish the host range of pGT633. The results revealed that pGT633 replicated autonomously and encoded constitutive resistance to erythromycin in a variety of bacterial hosts, including Bacillus subtilis BD170, Streptococcus sanguis DL1, Staphylococcus aureus RN4220, and Enterococcus faecalis 19433, as well as several Lactobacillus spp. A 2.2 kb BamHI fragment of pGT633 containing the genetic determinant (ermGT) encoding resistance to erythromycin was cloned into Escherichia coli. Determination of the nucleotide sequence of ermGT revealed a methylase gene 731 bp in length that was highly related (ca. 81% nucleotide and ca. 78% amino acid identity) to the ermC gene from S. aureus plasmid pE194. The leader sequences of ermGT and ermC were identical except for a single base change at nt 51.
Amino Acid Sequence↗
Molecular characterization of the DNA-binding and dimerization domains of the bZIP transcription factor, EmBP-1.
The wheat basic-leucine zipper (bZIP) DNA-binding protein EmBP-1 has been implicated in the mechanisms of abscisic acid (ABA) mediated gene regulation. Sequence and structural homology to the yeast bZIP protein GCN4 has been used to predict the location of the functional domains of EmBP-1. In order to test these predictions, the presumptive DNA-binding and dimerization domains of EmBP-1 were mapped by producing a series of truncated protein fragments and functionally testing them in vitro. Deletion of 5 amino acids of the predicted basic domain resulted in a loss of all DNA-binding activity. A fragment containing all six leucine repeat elements showed strong DNA-binding activity. Sequential deletion of the leucine repeat elements resulted in first an increase in DNA-binding activity (-L6 and -L5) followed by a reduction in binding activity (-L4) and eventually complete elimination of all detectable DNA-binding activity (-L3 and -L2). This demonstrates the importance of an intact leucine zipper domain of at least 4 repeat elements for efficient DNA-binding. The smallest polypeptide that retained DNA-binding activity is a fragment spanning amino acid residues 248-308 (ca. 8.4 kDa) consisting of minimal basic and leucine zipper domains. Dimerization of EmBP-1 was demonstrated by co-translation of fragments of differing molecular weights and identification of a DNA-protein complex with intermediate mobility to that produced by each fragment alone. A unique leucine-proline repeat element found N-terminal to the DNA-binding domain of EmBP-1 does not appear to play a role in DNA-binding or dimerization. These results confirm the locations of the functional domains of EmBP-1 predicted by similarity to GCN4. The high degree of functional conservation of the bZIP proteins spanning organisms from plants to fungi highlights the ancient origin of this class of transcription factors and of the mechanisms of gene regulation in which they participate.
Abscisic Acid↗
Long-term results in surgically managed esophageal achalasia.
The long-term clinical results of surgical treatment for esophageal achalasia were reviewed in 35 patients having a minimum follow-up of 10 years. Group A (n = 22) are those patients whose first procedure (myotomy and Belsey partial fundoplication) was done at our hospital. Group B (n = 13) are those who had undergone one or more previous operations elsewhere. In group A good to excellent results occurred in 21/22 patients (95%) at 1 year, 17/22 (77%) at 5 years, 15/22 (68%) at 10 years, 11/16 (69%) at 15 years, and 6/9 (67%) at 20 or more years. Two patients underwent early reoperation (2 and 5 years) for dysphagia due to incomplete myotomy. Three patients underwent esophagectomy (7, 19, and 23 years) and one patient underwent an antrectomy and Roux-en-Y diversion (23 years) for late-onset complications of reflux. Three of 13 group B patients had had multiple prior operations and had severe reflux damage at presentation and underwent immediate esophagectomy. Ten patients had one or more conservative operations in our hospital, and 4 of these eventually required esophagectomy for disabling reflux. Therefore, there were 10 patients (groups A+B) who underwent esophageal resection, all but 1 of whom had endoscopically documented reflux and 5 of whom had peptic strictures. Six of the 10 esophagectomies were performed more than 10 years (13 to 23 years) after the first operation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Clinical comparison of the Baxter MicroScan Yeast Identification Panel and the Vitek Yeast Biochemical Card.
To determine the reliability of the Baxter MicroScan Yeast Identification Panel, processed by the Walkaway-96, and the Vitek Yeast Biochemical Card, 150 clinical yeast isolates (30 Candida albicans, 67 Candida species, not albicans, 26 Torulopsis glabrata, 13 Cryptococcus neoformans, 4 Saccharomyces cerevisiae, 6 Trichosporon beigelii, 3 Rhodotorula species, and 1 Geotrichum species) were tested on both systems. Results were compared with those obtained by the API 20C and the appearance of yeast cells on cornmeal Tween-80 agar. After inoculation of each system, results were available in 4 hours with MicroScan panels, 24-48 hours with Vitek cards, and 72 hours with the API 20C strips. On initial testing, 101 (67%) and 128 (85%) isolates, respectively, were correctly identified by MicroScan and Vitek. After repeat testing, the number of correctly identified isolates increased to 123 (82%) by MicroScan and to 142 (95%) by Vitek. Yeasts most commonly misidentified were Candida tropicalis, T glabrata, and Candida parapsilosis by MicroScan and C tropicalis and T glabrata by Vitek.
Mycology↗
Experimentally induced septic arthritis in chimpanzees infected with Mycoplasma hominis, Mycoplasma pneumoniae, and Ureaplasma urealyticum.
Mycoplasma hominis was isolated in pure culture from septic synovial aspirates from an individual (patient A) during 16 different bouts of exacerbation over a 70-month period of observation. Two isolates, 10(7) and also 10(6) color-changing units (CCU) of the 1620 isolate and 5 x 10(4) CCU of the 1628 isolate, caused inflammation in chimpanzees inoculated intraarticularly. Inflammation was also induced with 10(7) CCU of the 2010B isolate, serovar VII of Ureaplasma urealyticum, recovered from an agammaglobulinemic individual (patient B) with septic polyarthritis and with 3 x 10(6) CCU of the PI-1428 isolate of Mycoplasma pneumoniae. Inflammation persisted for up to 36 days and was self-limiting. The aspirates contained up to 220,000 white blood cells/mm3 and up to 10(7) CCU/mL. There was good correlation between the severity of inflammation and the numbers of organisms, but antibody was not detected in aspirates during the peak severity of disease. As the numbers of organisms, decreased, detectable levels of antibody increased, thus suggesting that antibody may have been bound to antigen. Chimpanzees previously infected with either the 1628 isolate of M. hominis or the 2010B isolate of U. urealyticum were protected on challenge with > 100 times the minimal dose causing arthritis. Chimpanzees showed little or no inflammation when inoculated intraarticularly with 5 x 10(8) CCU of the type strain PG-21 of M. hominis or with the type strain CO of U. urealyticum or when inoculated intravenously with 3 x 10(8) CCU of the arthrogenic 1620 isolate of M. hominis.
Animals↗
Assessing patient dependence in Alzheimer's disease.
BACKGROUND: While cognitive and functional deficits are the hallmark of Alzheimer's disease (AD), loss of social function (and the dependence this implies) is also critical, especially in early stages of disease. Little attention has been directed to this facet of dementing disease. We describe a scale for assessing dependency in AD and present a baseline profile of dependency in a cohort of AD patients. METHODS: In a study of the predictors of the course of AD, 233 patients in early stages of disease (modified MMS > or = 30) were assessed. Psychometric properties of the dependence scale were established. To validate the scale, dependence scores at baseline were correlated with a series of measures assessing cognition and function. The course of dependency over 18 months of follow-up was also analyzed. RESULTS: The scale shows adequate reliability (test-retest, intraclass correlation). Dependence stage was related to other measures of disease severity. Scalogram analysis shows that the dependence scale is consistent with the course of functional loss established for dementing disease. Prospective data indicate sensitivity of the scale to disease progression. CONCLUSION: Dependency is a distinct, measurable component of dementing disease and should be considered an important outcome in studies of AD.
Activities of Daily Living↗
Hypertriglyceridemic serum, very low density lipoprotein, and iron enhance Mycobacterium avium replication in human macrophages.
The growth of Mycobacterium avium 7497, serovar 4, in cultured human macrophages is enhanced by Fe3+ and serum lipids over 7 days. Iron (1-80 micrograms/mL) added to macrophages cultured in normal serum resulted in 10-fold increases in growth. If iron-supplemented macrophages were cultured in serum from hypertriglyceridemic donors after infection, M. avium growth increased 10(3)- to 10(4)-fold. Without macrophages, differences in bacterial growth between sera were not seen. Removal of very low density lipoprotein (VLDL) eliminated the differences between sera. Isolated VLDL from hyperlipidemic serum resulted in 10(5)-fold increases in growth over that seen with VLDL from normal sera. Accelerated M. avium growth in macrophages cultured with hyperlipidemic serum was partly inhibited by the addition of superoxide dismutase (1000 IU/mL). Results suggest that iron stimulates O2-induced oxidation of VLDL and its subsequent accumulation in macrophages. The resultant iron- and lipid-laden cells become excellent hosts for mycobacterial growth.
Acquired Immunodeficiency Syndrome↗
A dose intensity study of FLAC (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy and Escherichia coli-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) in advanced breast cancer patients.
BACKGROUND: It has been demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) can ameliorate chemotherapy-induced neutropenia. The extent to which GM-CSF can increase the actual delivered dose intensity of combination chemotherapy over multiple cycles of therapy to patients with advanced breast cancer has not been well defined. We conducted a phase I/II study of dose-intensive FLAC chemotherapy (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) in combination with GM-CSF in patients with locally advanced and metastatic breast cancer to study the acute and cumulative toxicities, anti-tumor activity and dose-intensity achievable with this regimen. METHODS: Eighty-one patients with newly diagnosed stages IIB, III and IV breast cancer who were previously untreated with chemotherapy and who had measurable disease received multiple cycles of FLAC chemotherapy plus E. coli-derived GM-CSF administered every three weeks. RESULTS: FLAC plus GM-CSF as associated with significant cumulative hematologic toxicity. Ninety-eight percent of patients developed grade 4 neutropenia; 29% of all cycles administered required hospitalization for fever and neutropenia; 41% and 22% of cycles required red blood cell and platelet transfusions, respectively. Other significant toxicities with E. coli-derived GM-CSF included mild to moderate first dose effects (hypotension, dyspnea, abdominal cramping) in 30% of patients; late occurring anaphylactoid reactions in 11% of patients; and vascular thromboses. The average delivered dose intensities over all cycles were cyclophosphamide, 210 mg/m2/week; doxorubicin, 14.8 mg/m2/week and 5-fluorouracil, 342 mg/m2/week. The overall clinical response rates were 100% and 83% for LABC and metastatic patients, respectively. There were 23% (6/26) pathologic CR's in the LABC patients given neoadjuvant FLAC and 22% (12/54) clinical CR's in the stage IV patients. The median survival of the LABC patients has not been reached (> 26 months) and is 30 months for the stage IV patients. CONCLUSIONS: The administration of multiple cycles of FLAC plus E. coli-derived GM-CSF therapy is associated with cumulative, dose-limiting myelosuppression, especially thrombocytopenia, as well as significant clinical toxicity. A modest increase in FLAC dose intensity over the starting doses was achievable with the addition of GM-CSF. FLAC chemotherapy has substantial antitumor activity in the treatment of advanced breast cancer. The potential usefulness of FLAC plus GM-CSF must be balanced by its considerable cost and alteration in patients' quality of life due to toxicity. Combination hematopoietic growth factor strategies may be able to reduce the toxicity of FLAC and to allow further increase dose intensity.
Adult↗
Magnetic resonance imaging of in situ mammary prostheses.
A study was conducted at the University of Virginia Health Sciences Center to examine the effectiveness of magnetic resonance imaging in detecting rupture or deflation of in situ mammary prostheses. Thirty-three women with 59 prostheses were included in the study. Fifteen of the 33 patients had undergone surgery for removal or replacement of 21 implants. Positive findings for rupture were accurately predicted for 15 implants and confirmed at surgery. Negative findings for rupture were accurately predicted in the remaining 6 implants and confirmed at surgery. Although it is a more costly procedure than either mammography or ultrasonography, we believe that magnetic resonance imaging is also more accurate in detecting damaged implants, particularly when they are contained within an intact capsule or when the implants are stacked. Unlike mammography, magnetic resonance imaging requires no ionizing radiation or breast compression. Magnetic resonance imaging of the in situ breast prosthesis may be a useful adjunct when other modalities yield inconclusive results or when a contained rupture is suspected.
Adolescent↗
Prevention of "temporal hollowing" after fronto-orbital advancement for craniosynostosis.
Depression of profile in the temporal region is commonly seen after orbital rim advancement procedures. A newly developed temporalis musculoosseous flap has been designed with the intent to prevent this postoperative occurrence.
Craniosynostoses↗
Achalasia in Down's syndrome.
Gastrointestinal disorders, including motor disorders of the esophagus, occur more frequently in patients with Down's syndrome than in the general population. We recently diagnosed achalasia in a man with Down's syndrome, an association reported only once before. Of the 643 patients with achalasia treated at our institution over a 30-year period (1962-1992), a total of three had Down's syndrome. We report their clinical, radiological, and manometric findings. Achalasia may be underdiagnosed in patients with Down's syndrome because their intellectual impairment may interfere with their ability to report symptoms adequately. All three patients responded well to conventional treatment.
Adult↗
Establishing partnerships with family caregivers. Local and cosmopolitan knowledge.
1. The concepts of local and cosmopolitan knowledge may be used by gerontological nurses in creating partnerships with family caregivers to frail older people. 2. Local knowledge is the understanding and skills that the family brings to the caregiving situation; cosmopolitan knowledge is the understanding and skills that the gerontological nurse brings to the situation. 3. Four nursing interventions are guided by the conceptualization of local and cosmopolitan knowledge: acknowledging and affirming local knowledge when it is adequate; developing or enhancing local knowledge when it is inadequate; assisting family caregivers to apply local knowledge to problem solving; and blending local and cosmopolitan knowledge.
Aged↗
Commercial isotope venture from defunct SSC.
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Cancer Care Facilities↗