Nursing home ownership revisited: market, cost and quality relationships.
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Bed Occupancy↗
Biomedical subjects
M A Davis
Publications and source records attributed to M A Davis.
Fine-structure analysis of the P7 plasmid partition site.
The par region of bacteriophage P7 is responsible for active partition of the P7 plasmid prophage into daughter cells. The cis-acting partition site was defined precisely as a 75-bp sequence that was necessary and sufficient to promote correct segregation of an unstable vector plasmid when the two P7 partition proteins, ParA and ParB, were supplied in trans. Roughly the same region was necessary to exert partition-mediated incompatibility. The minimal site contains an integration host factor (IHF) protein binding site bracketed by regions containing heptamer repeat sequences that individually bind ParB. An additional sequence forms the left boundary of the site. Site-directed mutations in the latter sequence, as well as the IHF motif and the rightmost ParB box, blocked site function. Although the P7 site shares 55% sequence identity with its counterpart in bacteriophage P1, functional interactions between the partition sites and the Par proteins of the two plasmids were entirely species specific in vivo. The P1 sequence has similar IHF and ParB binding motifs, but the left boundary sequence differs radically and may define a point of species-specific contact with the Par proteins. No evidence was found for the existence of a functional P7 analog of the P1 parS core, a small subregion of the P1 site that, in isolation, acts as an enfeebled partition site with modified incompatibility properties.
Bacterial Proteins↗
Effects of a novel NMDA antagonist on experimental stroke rapidly and quantitatively assessed by diffusion-weighted MRI.
We employed diffusion-weighted MRI (DWI) to identify regions of focal brain ischemia during the first 3 hours after permanent occlusion of the middle cerebral artery in rats. Using DWI as early as 30 minutes after the onset of ischemia, it was possible to identify the areas of brain destined to progress to infarction over the next 24 hours in untreated animals, as demonstrated by postmortem evaluation. DWI studies revealed the cerebroprotective effects of a noncompetitive N-methyl-D-aspartate receptor antagonist, CNS 1102, administered 15 minutes postocclusion, both on the cortical and caudoputaminal regions during the initial 3 hours of ischemia. Although the treatment effect lessened over the next 21 hours in a few animals with lower plasma drug levels at 3 hours, postmortem studies demonstrated a 66% reduction in the total volume of infarcted tissue with the treatment and confirmed the DWI results. T2-weighted MRI obtained at similar times revealed little or no abnormality. These results suggest that DWI provides a sensitive in vivo measure of focal cerebral ischemic injury and can assess the beneficial effects of cytoprotective therapy. DWI may be useful in the early evaluation of human stroke patients and in monitoring the effects of cerebroprotective therapies in the clinical setting.
Animals↗
In vitro metabolism of cyanohydroxybutene: formation of a glutathione-S-transferase catalyzed product.
The pancreatotoxin cyanohydroxybutene (CHB) causes a significant and prolonged elevation in glutathione (GSH) in liver and pancreas (Wallig and Jeffery, 1990). Here we report that urinary thiols also increase. This suggests that CHB may react with GSH, either directly or following phase I oxidation, to form an adduct, which is further metabolized to the corresponding mercapturic acid for urinary excretion. Metabolism of CHB by hepatic mixed function oxidase and cytosolic alcohol dehydrogenase enzymes was evaluated by monitoring microsomal NADPH consumption and alcohol dehydrogenase-dependent NADH generation, respectively. There was no apparent increase in the rate of microsomal NADPH consumption or alcohol dehydrogenase-dependent NADH generation in the presence of CHB. To evaluate in vitro formation of a glutathione-S-transferase (GST) catalyzed adduct, [3H-glycyl]-GSH and [14C-cyano]-CHB were incubated at 37 degrees C for 1 h, with or without GST. Dinitrophenol derivatization and high performance liquid chromatographic (HPLC) analysis (Farris & Reed, 1987) revealed no double-labeled peaks, suggesting that no stable conjugate was formed. However a tritiated product, not present in control samples, and with an identical retention time to cysteinyl-glycine (cys-gly) was formed. In addition, the product has a fast atom bombardment mass-spectrum consistent with cys-gly. These results suggest that while CHB may not undergo phase I oxidation, in the presence of CHB, GSH may break down to form cys-gly. A mechanism for CHB-dependent breakdown of GSH to cys-gly is proposed, and the pharmacological implications of this finding are discussed.
Alcohol Dehydrogenase↗
Structural and functional analysis of the amdR regulatory gene of Aspergillus oryzae.
We have isolated the Aspergillus oryzae homologue of the amdR regulatory gene of Aspergillus nidulans by cross hybridization. Sequence analysis and functional studies have shown that the amdR genes are highly conserved and functionally interchangeable between the two species. The homology between the two genes extends throughout most of the coding sequences, including sequences encoding the DNA-binding domain and putative activation domains. Two regions of nonconserved sequence were also identified. Studies using various amdS::lacZ fusion constructs indicate that the A. oryzae gene product binds similar sequences and responds to inducer in a similar manner to the A. nidulans protein. Inactivation of the A. oryzae gene results in the inability to grow on gamma-amino-butyric acid (GABA) as a carbon and/or nitrogen source indicating that GABA utilization is amdR-dependent in A. oryzae as it is in A. nidulans.
Amino Acid Sequence↗
The potential superiority of bromodeoxyuridine to iododeoxyuridine as a radiation sensitizer in the treatment of colorectal cancer.
Although the thymidine analogues 5-bromo-2'-deoxyuridine (BrdUrd) and 5-iodo-2'-deoxyuridine (IdUrd) have been used successfully as radiation sensitizers in clinical trials, it is not clear which of these agents is the more promising to pursue. To begin to assess this question with regard to colorectal cancer metastatic to the liver, a study was carried out using HT29 human colon cancer cells in culture and implanted in nude mice as xenografts. Cells and animals were treated with BrdUrd +/- the thymidylate synthase inhibitor 5-fluoro-2'-deoxyuridine (FdUrd), and the results compared to our previous studies with IdUrd +/- FdUrd (T. S. Lawrence, M. A. Davis, P. E. McKeever, J. Maybaum, P. L. Stetson, D. P. Normolle, and W. D. Ensminger. Cancer Res., 51: 3900-3905, 1991). Using cultured cells, it was found that FdUrd (at concentrations of greater than 10 nM) increased: (a) the incorporation of BrdUrd into the DNA of cultured tumor cells; (b) BrdUrd-mediated radiosensitization; (c) BrdUrd-mediated increase in radiation-induced DNA damage; and (d) BrdUrd-mediated decrease in the repair of radiation-induced damage. The incorporation of BrdUrd was greater than or equal to the incorporation of IdUrd previously determined under the same exposure conditions. Studies using nude mice bearing HT29 xenografts showed that FdUrd increased BrdUrd incorporation more into tumors than into the normal liver. Most tumor cells incorporated BrdUrd (labeling index after a 4-day infusion = 87 +/- 2%; SE); in the liver, labeling was confined chiefly to nonparenchymal cells. In both the presence and absence of FdUrd, the incorporation of BrdUrd into tumors was significantly and consistently greater than the incorporation of IdUrd measured under the same conditions of drug administration (by a factor of 1.2-3.6). Furthermore, the administration of BrdUrd +/- FdUrd tended to produce less weight loss and hematological toxicity than IdUrd +/- FdUrd. These findings suggest that BrdUrd may be superior to IdUrd as a radiation sensitizer in the treatment of colorectal cancer metastatic to the liver.
Animals↗
Effect of recombinant alpha interferons on fertility and interestrous interval in sheep.
In Experiment 1, 12 unmated cyclic ewes received twice-daily intrauterine injections on Days 12 to 14 of one of the following treatments: 1) ovine conceptus secretory proteins (oCSP) containing 25 microg of ovine trophoblast protein-1 (oTP-1) as determined by RIA; 2) 25 or 50 microg recombinant human interferon alpha1 (rhlFN); or 3) 1500 microg of serum proteins (oSP) from a Day-16 pregnant ewe (estrus = Day 0) per uterine horn. Ewes receiving oCSP had longer interestrous intervals (27 +/- 2 days; P<0.05) than ewes receiving oSP (17 +/- 2 days). Ewes receiving either dose of rhlFN had an interestrous interval of 16 +/- 2 days which did not differ (P>0.10) from that of oSP-treated ewes. In Experiment 2, 59 normally cycling ewes, mated on Day 0, received twice-daily intramuscular injections of either 2 mg recombinant bovine interferon alpha1 (rblFN) or placebo on Days 12 to 15 post estrus. On Day 16, pregnancy was confirmed by flushing a morphologically normal conceptus from the uterus. Pregnancy rates for rblFN-treated (80%) and placebo-treated (62%) ewes were not different (P>0.10). Uterine flushings and conceptus-conditioned medium were assayed for oTP-1. Total oTP-1 in conceptus-conditioned culture medium was higher (P<0.02) when conceptuses were from placebo-treated (104 +/- 14 microg/conceptus) than from rblFN-treated (56 +/- 12 microg/conceptus) ewes; while total oTP-1 in uterine flushings was similar (P>0.10) for placebo-treated (132 +/- 15 microg/conceptus) and rblFN-treated (147 +/- 17 microg/conceptus) ewes. The interval from mating to subsequent estrus following conceptus removal was 31 +/- 1 and 28 +/- 1 days for pregnant ewes treated with rblFN and placebo, respectively. Interestrous intervals for nonpregnant ewes were longer (P<0.02) for rblFN-treated (27 +/- 3 days) than for placebo-treated (18 +/- 2 days) ewes.
Journal Article↗
Modulation of iododeoxyuridine-mediated radiosensitization by 5-fluorouracil in human colon cancer cells.
The incorporation of 5-iodo-2'-deoxyuridine (IdUrd), a thymidine analog radiosensitizer, can be increased by the use of modulators such as 5-fluorouracil (FUra). FUra is a particularly attractive potential modulator to use against colorectal cancer, as it is the most active single agent in the treatment of this disease. To begin to define the conditions for the optimal combination of IdUrd and FUra in the treatment of patients with colorectal cancer, a study was conducted of the effect of FUra on IdUrd-mediated radiosensitization in cultured HT29 human colon cancer cells. It was found that when cells were exposed to concentrations of IdUrd typical of those obtained through intravenous exposure (1-3 microM), FUra (1 microM) increased radiosensitization beyond that which would be predicted for the same extent of incorporation produced by incubation with IdUrd alone. This increase appeared to result from a combination of at least two effects: FUra-mediated cell cycle redistribution and increased IdUrd incorporation. When a higher concentration of IdUrd (10 microM) was used with FUra (1 microM), cell cycle distribution returned to nearly normal, and radiosensitization was equal to that predicted by the extent of incorporation of IdUrd. These data demonstrate that the combination of FUra and IdUrd can produce radiosensitization both through increased IdUrd incorporation and cell cycle redistribution. Furthermore, they suggest that, in the presence of a modulator, it may not be necessary to achieve high levels of IdUrd incorporation to produce significant tumor radiosensitization.
Cell Cycle↗
Prevention of urinary tract infection and bacteremia following transurethral surgery: oral lomefloxacin compared to parenteral cefotaxime.
A multicenter, randomized, open label study compared the safety and efficacy of a single dose of oral lomefloxacin, a broad-spectrum antimicrobial agent of the quinolone class, to a single parenteral dose of cefotaxime, a third generation cephalosporin, for prophylaxis in transurethral surgery. Of the 230 patients initially recruited 182 were considered evaluable: 92 in the lomefloxacin group and 90 in the cefotaxime group. Both study groups were well balanced with respect to demographics and transurethral procedures. Efficacy and safety were evaluated with urine cultures, clinical laboratory evaluations and monitoring of adverse events. The success rate among the lomefloxacin patients was 98% versus 94% in the cefotaxime patients. The difference was not statistically significant. Adverse events, regardless of attributability, were reported by 16% of the lomefloxacin patients and 17% of the cefotaxime patients, respectively. Our results indicate efficacy and safety profiles of lomefloxacin equivalent to cefotaxime. Lomefloxacin has the economic advantage of an oral route of administration compared to the parenteral route of cefotaxime for prophylaxis in transurethral genitourinary procedures.
Administration, Oral↗
In vitro dissolution of cholesterol gallstones.
RATIONALE AND OBJECTIVES: Methyl tert-butyl ether (MTBE) is the solvent most commonly used for in vivo dissolution of cholesterol gallstones. Its limitations, however, include high volatility and flammability along with potential toxicologic concerns. Therapy may take several hours. This study was initiated to identify alternate solvents which may be superior to MTBE in one or more of these areas. METHODS: MTBE was compared with several other solvents for cholesterol-dissolving capacity. Groups of human cholesterol gallstones were placed in test tubes, and, without agitation, subjected to mixtures of MTBE:ethanol or another solvent:ethanol. RESULTS: Six other solvents were found to have higher capacities. In several cases, other solvent mixtures dissolved gallstones up to twice as fast as the MTBE:ethanol mixture. These faster solvents were cyclic ethers (tetrahydrofuran [THF], methyl tetrahydrofuran [MTHF], tetrahydropyran [THP], methyl tetrahydropyran [MTHP], and possibly dimethyl tetrahydrofuran [DMTHF]) and limonene. Some of these solvents also have lower volatility and higher flash points than MTBE, resulting in safer storage and handling. THF and pyridine, however, were found to precipitate bile components when mixed with bile. CONCLUSION: The authors describe solvents that may be superior to MTBE for rapid dissolution of gallstones in vivo.
Cholelithiasis↗
Biochemical activities of the parA partition protein of the P1 plasmid.
The unit-copy P1 plasmid depends for stability on a plasmid-encoded partition region called par, consisting of the parA and parB genes and the parS site. ParA is absolutely required for partition, but its partition-critical role is not known. Purified ParA protein is shown to possess an ATPase activity in vitro which is specifically stimulated by purified ParB protein and by DNA. ParA is responsible for regulation of expression of parA and parB, and purified ParA has an ATP-dependent, site-specific DNA binding activity which recognizes a sequence that overlaps the parA promoter. The role of the ATP-dependence of the binding activity, as well as other possible functions of the ATPase activity in partition, is discussed.
Adenosine Triphosphatases↗
Identification of functional regions of the positively acting regulatory gene amdR from Aspergillus nidulans.
The amdR (intA) regulatory gene of Aspergillus nidulans encodes a 765-amino-acid polypeptide which determines the omega-amino acid induction of at least five structural genes. The AmdR polypeptide contains a potential Zn(II)2Cys6 DNA-binding motif which has been shown to be present in the N-terminal region of a large number of fungal activator proteins. In vitro mutagenesis of the fourth cysteine of this motif abolishes AmdR function as shown by loss of complementation of an amdR- mutation and by the AmdR- phenotype of a mutant gene replacement strain. Studies using constructs in which the proposed AmdR DNA-binding motif is replaced with that from another activator, FacB, shows that induction is independent of DNA-binding specificity and that sequences in the C-terminal region of AmdR are activation domains. Sequencing of several amdR mutant alleles which affect activation and/or induction, together with studies of deletion constructs indicate that changes in the conformation of the protein determines its activity and that this is modulated by inducers.
Aspergillus nidulans↗
Is calcium oxalate an adequate explanation for nonvisualization of breast specimen calcifications?
This study was initiated to determine whether the apparent calcium loss during histologic breast specimen processing could be explained by the presence of birefringent, transparent calcium oxalate crystals (type I). In previous investigations, the authors had noted a possible loss of 26.2% of calcium during the processing and sectioning of breast specimens. Two hundred thirteen histologic slides prepared from blocks demonstrating calcium radiographically but not histologically were reviewed with polarized light. An additional 506 slides from 19 malignancies appearing as microcalcifications were also reviewed with polarized light. Only one slide from each group (0.2% and 0.5% from the malignant and benign groups, respectively) demonstrated birefringent calcium oxalate (type I). Thus, the presence of calcium oxalate does not sufficiently explain the non-visualization of calcium, which is due instead to processing of breast specimens.
Biopsy↗
Reversible focal ischemic injury demonstrated by diffusion-weighted magnetic resonance imaging in rats.
BACKGROUND AND PURPOSE: Diffusion-weighted magnetic resonance imaging (DWI) can quantitatively display focal brain abnormalities within minutes after the onset of ischemia. We performed the present study to determine the effects of 1 and 2 hours of temporary ischemia on DWI. METHODS: We examined DWI and T2-weighted magnetic resonance images (T2WI) during and after 1 and 2 hours of temporary middle cerebral artery occlusion in rats (n = 10 for each group). In a subgroup of four animals from each group, we employed perfusion magnetic resonance imaging to monitor cerebral perfusion. Neurological outcome and infarct size after survival for 24 hours were compared between the groups and correlated with DWI and T2WI studies. RESULTS: Perfusion studies qualitatively documented hypoperfusion and reperfusion during and after temporary occlusion. Lesion size on DWI during reperfusion was significantly less than that during ischemia for 1 (55% decline, p less than 0.02) but not 2 hours of occlusion. The DWI signal intensity ratio (intensity compared with that in the contralateral homologous area) just before withdrawal of the occluder was significantly less in regions where the hyperintensity disappeared after withdrawal than in regions with persistent hyperintensity (p less than 0.002). The T2WI studies revealed few or no abnormalities, except after 2 hours of occlusion. The neurological outcome was significantly better in the 1-hour than in the 2-hour group (p less than 0.05). Postmortem infarct volume was significantly smaller in the 1-hour group than in the 2-hour group (p less than 0.05). The postwithdrawal DWI accurately predicted infarct size (R = 0.96, p less than 0.0001). CONCLUSIONS: The present study indicates that DWI can rapidly display not only irreversible but also reversible ischemic brain damage and enhances the importance of DWI as a diagnostic modality for stroke.
Animals↗
Diffusion-weighted magnetic resonance imaging: rapid and quantitative detection of focal brain ischemia.
We examined serial changes of diffusion- (DWI) and T2-weighted (T2WI) magnetic resonance images 30 minutes to 3 hours after intraluminal suture occlusion of the middle cerebral artery (MCA) in eight rats and after sham occlusion in four. We correlated the abnormal areas on DWI and T2WI with postmortem areas of infarction determined by 2,3,5-triphenyltetrazolium chloride (TTC), 24 hours after the operation. The 30-minute DWI in each MCA-occluded rat demonstrated increased signal intensity in the ipsilateral MCA territory, while T2WI showed no changes. At 3 hours, the ipsilateral DWI signal intensity increased further and the area of abnormality slightly increased. In some animals, the 3-hour T2WI disclosed an area of hyperintensity significantly smaller than that seen on the 30-minute DWI. TTC staining demonstrated an extensive MCA infarction in all rats with permanent MCA occlusion, confirmed by hematoxylin and eosin staining. The percent infarcted area of coronal brain sections, as determined by TTC staining, correlated significantly with areas on similar DWI sections at both 30 minutes and 3 hours. Sham-occluded control animals did not display any changes on DWI, T2WI, or TTC staining. The present study suggests that DWI is a very sensitive modality for detecting early ischemic brain injury, being highly correlated with post-mortem area of infarction, and may be useful to assess pharmacologic intervention.
Animals↗
Effects of ovine conceptus secretory proteins and progesterone on oxytocin-stimulated endometrial production of prostaglandin and turnover of inositol phosphate in ovariectomized ewes.
This study examined the effects of progesterone and intrauterine injection of ovine conceptus secretory proteins (oCSP) on endometrial responsiveness to oxytocin. Twelve ewes were ovariectomized on day 4 of the cycle (oestrus = day 0) and assigned in a 2 x 2 factorial arrangement, to receive either 1.5 mg ovine serum proteins (SP) or oCSP containing 25 micrograms ovine trophoblast protein 1 (oTP-1) (by radioimmunoassay) in 1.5 mg total protein into each uterine horn, via catheters, twice a day on days 11, 12, 13 and 14. Ewes received 200 mg progesterone per day (i.m.) from day 4 to day 10 or 15. Oxytocin-induced prostaglandin F2 alpha was measured as 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) on days 11, 12, 13 and 14 in plasma from three integrated, 10 min (10 ml) blood samples (0-10, 10-20, 20-30 min) obtained after intravenous injection of 20 iu oxytocin, and in a pre-oxytocin (-10 to 0 min) sample collected via an indwelling jugular catheter. The pre-oxytocin samples were also assayed for progesterone. Oxytocin-induced turnover of inositol phosphate was determined in endometrium on day 15 after hysterectomy. In ewes receiving progesterone to day 10, plasma progesterone decreased from about 12 to 2 ng ml-1 (SEM +/- 2.6) during the treatment period (days 11-14), but remained high (12-20 +/- 2.6 ng ml-1) in ewes that received progesterone to day 15. Intrauterine injection of oCSP resulted in high basal concentrations of PGFM on days 12 and 13 compared with SP-treated ewes (P less than 0.01). Treatments with progesterone did not affect basal PGFM concentrations. Treatment with oCSP abolished oxytocin-induced endometrial secretion of prostaglandin only if progesterone was maintained to day 15 (P less than 0.01); in ewes receiving such treatment, oCSP inhibited (P less than 0.01), but SP did not inhibit, oxytocin-induced endometrial turnover of inositol phosphate (P less than 0.06), which was greater in ewes treated with progesterone to day 10 than in those treated to day 15 (P less than 0.05). Ewes that responded to oxytocin with increased PGFM exhibited increased oxytocin-stimulated turnover of inositol phosphate on day 15. These results indicate that the antiluteolytic action oTP-1 exerts on the endometrium requires progesterone and that this mechanism involves inhibition of oxytocin-stimulated turnover of inositol phosphate.
Animals↗
Living arrangements and survival among middle-aged and older adults in the NHANES I epidemiologic follow-up study.
BACKGROUND: There is concern about but little information on how living alone affects the health and survival of older adults. METHODS: We examined the association between living arrangements (living alone, with a spouse, or with someone other than a spouse) and survival among 7651 adults, aged 45 to 74 years in the National Health and Nutrition Examination Survey (NHANES I) (1971-1975) and traced at the NHANES I Follow-up Study (1982-1984), to see whether certain sociodemographic factors (race, education, income, and employment), health behaviors (alcohol, smoking, physical activity, and obesity), or chronic medical conditions were influential in the association. RESULTS: We found a stronger association of living arrangements with survival for men than for women, and for middle-aged men than for older men. For men, those living alone and those living with someone other than a spouse were equally disadvantaged in terms of survival. Income, race, employment, and physical activity influenced the association of living arrangements and survival, but their impact varied by age, gender, and living arrangement. CONCLUSION: Living arrangements had a weak impact on survival among men, but had no effect among women.
Age Factors↗
Correlates of knee pain among US adults with and without radiographic knee osteoarthritis.
We examined the associations of sociodemographic variables, health behaviors, health status and psychological well being with radiographic knee osteoarthritis (OA) and self-reported knee pain for 4056 US adults aged 45-74 years. Among persons with or without knee OA known correlates of radiographic knee OA (age, sex, race, obesity) were generally not associated with knee pain. Radiographic severity, psychological well being and health status were associated with knee pain, both among persons with and without radiographic knee OA, suggesting that nonradiographic correlates of self-reported knee pain are independent of whether a person has radiographic knee OA.
Age Factors↗