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Biomedical subjects

D Klein

Publications and source records attributed to D Klein.

At least 55 records · Page 3Linked to original sources

Genetic targeting: the serotonin N-acetyltransferase promoter imparts circadian expression selectively in the pineal gland and retina of transgenic rats.

The arylalkylamine N-acetyltransferase (AA-NAT) gene is strongly expressed in the rat primarily in the pineal gland; low levels of expression are also found in the retina. AA-NAT catalyzes the key regulatory step controlling rhythmic melatonin output: the acetylation of serotonin. In the rat, the AA-NAT gene is expressed at night. This is controlled partly by cyclic AMP (cAMP) acting through a composite cAMP-responsive element-CCAAT site located upstream of the transcription start point. In the present study, we have extended our previous in vitro findings and found that additional elements in the 5' flanking region and first intron play an important role in the regulation of the AA-NAT gene. This led us to test the influence of an AA-NAT 5' flanking segment on the expression of the bacterial chloramphenicol acetyltransferase gene in a rat transgenic model. The results of this study clearly demonstrate that the segment of the AA-NAT gene that encompasses the minimal promoter and the first intron is able to confer the highly specific pineal/retinal and time-of-day patterns of AA-NAT gene expression. This advance also provides a tool that selectively targets genetic expression to pinealocytes and retinal photoreceptors, providing new experimental opportunities to probe gene expression in these tissues.

Animals↗

Striving toward continuous quality improvement: a case study of Saint Mary's Hospital.

This case analysis is the result of a year-long study designed to identify and assess the ingredients that led to the successful implementation of a continuous quality improvement (CQI) program at Saint Mary's Hospital in Grand Rapids, Michigan. The key ingredients of success included: (1) an organizational structure and leadership commitment for identifying and improving processes, (2) use of data-based statistical and analytical tools to study processes, (3) empowerment of teams of employees to take charge of the operations of their own work tasks in a manner that encourages continuous learning, (4) involvement of internal and external customers through the improvement process, and (5) development of effective measures for monitoring improvement. The benefits of the CQI efforts at Saint Mary's have been remarkable and hospital-wide.

Critical Pathways↗

The collaboration process in HIV prevention and evaluation in an urban American Indian clinic for women.

Collaboration between providers and researchers can be key to doing women's HIV prevention that is holistic, gender sensitive, and responsive to communities. This report centers on providers' and evaluators' experiences in developing and implementing a project promoting "healthy relationships" with low-income women from different ethnicities at an urban American Indian clinic. During planning, decisions on the health problems to be targeted, division of labor, program goals, resource allocation, evaluation design, and outcome measures were jointly made. Other factors were the input of participants and the influence of American Indian values at the clinic. The implementation process was fully collaborative. There are implications for creating conditions for successful collaborations in health education.

Community Networks↗

Forming collaborative relationships.

No more separate assessments--the Collaborative History and Physical form facilitates communication between nurses and physicians while it decreases duplication of data and increases patient satisfaction.

Cooperative Behavior↗

Maintenance phase efficacy of sertraline for chronic depression: a randomized controlled trial.

CONTEXT: The chronic form of major depression is associated with a high rate of prevalence and disability, but no controlled research has examined the impact of long-term treatment on the course and burden of illness. OBJECTIVE: To determine if maintenance therapy with sertraline hydrochloride can effectively prevent recurrence of depression in the high-risk group of patients experiencing chronic major depression or major depression with antecedent dysthymic disorder ("double depression"). DESIGN: A 76-week randomized, double-blind, parallel-group study, conducted from September 1993 to November 1996. SETTING: Outpatient psychiatric clinics at 10 academic medical centers and 2 clinical research centers. INTERVENTION: Maintenance treatment with either sertraline hydrochloride (n = 77) in flexible doses up to 200 mg or placebo (n = 84). PATIENTS: A total of 161 outpatients with chronic major or double depression who responded to sertraline in a 12-week, double-blind, acute-phase treatment trial and continued to have a satisfactory therapeutic response during a subsequent 4-month continuation phase. MAIN OUTCOME MEASURE: Time to recurrence of major depression. RESULTS: Sertraline afforded significantly greater prophylaxis against recurrence than did placebo (5 [6%] of 77 in the sertraline group vs 19 [23%] of 84 in the placebo group; P = .002 for the log-rank test of time-to-recurrence distributions). Clinically significant depressive symptoms reemerged in 20 (26%) of 77 patients treated with sertraline vs 42 (50%) of 84 patients who received placebo (P = .001). With use of a Cox proportional hazards model, patients receiving placebo were 4.07 times more likely (95% CI, 1.51-10.95; P = .005) to experience a depression recurrence, after adjustment for study site, type of depression, and randomization strata. CONCLUSIONS: Maintenance therapy with sertraline is well tolerated and has significant efficacy in preventing recurrence or reemergence of depression in chronically depressed patients.

Adult↗

Composition of parental mitochondrial DNA in cloned bovine embryos.

We have investigated parental mitochondrial DNA (mtDNA) in cloned bovine embryos obtained by intraspecific cytoplast-blastomere fusion. Analysis of two-cell to blastocyst stage embryos revealed that in contrast to the exclusion of paternal (sperm) mtDNA during sexual inheritance in the cytoplast-blastomere fusion complexes, there was mixing and co-existence of parental mtDNA. The mixing of mtDNA was non-balanced with the minority deriving from the blastomere. The constant content of mtDNA during embryogenesis until the blastocyst stage suggesting an absence of mtDNA replication was shown for conventional 'in vitro fertilised' (IVF) embryos and for cloned embryos. The ratio of parental mtDNA was in accordance with the estimated quantitative participation of mtDNA from the fusion partners.

Animals↗

Growth of tobacco in short-day conditions leads to high starch, low sugars, altered diurnal changes in the Nia transcript and low nitrate reductase activity, and inhibition of amino acid synthesis.

Diurnal changes in carbohydrates and nitrate reductase (NR) activity were compared in tobacco (Nicotiana tabacum. L.cv. Gatersleben) plants growing in a long (18 h light/6 h dark) and a short (6 h light/18 h dark) day growth regime, or after short-term changes in the light regime. In long-day-grown plants, source leaves contained high levels of sugars throughout the light and dark periods. In short-day-grown plants, levels of sucrose and reducing sugars were very low at the end of the night and, although they rose during the light period, remained much lower than in long days and declined to very low levels again by the middle of the night. Starch accumulated more rapidly in short-day-than long-day-grown plants. Starch was completely remobilised during the night in short days, but not in long days. A single short day/long night cycle sufficed to stimulate starch accumulation during the following light period. In long-day-grown plants, the Nia transcript level was high at the end of the night, decreased during the day, and recovered gradually during the night. In short-day-grown plants, the Nia transcript level was relatively low at the end of the night, decreased to very low levels at the end of the light period, increased to a marked maximum in the middle of the night, and decreased during the last 5 h of the dark period. In long-day-grown plants, NR activity in source leaves rose by 2- to 3-fold in the first part of the light period and decreased in the second part of the light period. In short-day-grown plants, NR activity was low at the end of the night, and only increased slightly after illumination. Dark inactivation of source-leaf NR was partially reversed in long-day-grown plants, but not in short day-grown plants. In both growth regimes, mutants with one instead of four functional copies of the Nia gene had a 60% reduction in maximum NR activity in the source leaves, compared to wild-type plants. The diurnal changes in NR activity were almost completely suppressed in the mutants in long days, whereas the mutants showed similar or slightly larger diurnal changes than wild-type plants in short days. When short-day-grown plants were transferred to long-day conditions for 3 d, NR activity and the diurnal changes in NR activity resembled those in long-day-grown plants. Phloem export from source leaves of short-day-grown plants was partially inhibited by applying a cold-girdle for one light and dark cycle. The resulting increase in leaf sugar was accompanied by an marked increase in the Nia transcript level and a 2-fold increase in NR activity at the end of the dark period. When wild-type plants were subjected to a single short day/long night cycle of increasing severity, NR activity in source leaves at the end of the night decreased when the endogenous sugars declined below about 3 mumol hexose (g FW)-1. In sink leaves in short-day conditions, sugars were higher and the light-induced rise in NR activity was much larger than in source leaves on the same plants. The source leaves of wild-type plants in short-day conditions contained very high levels of nitrate, very low levels of glutamine, low levels of total amino acids, and lower protein and chlorophyll, compared to long-day-grown plants. Plants grown in short days had relatively high levels of glutamate and aspartate, and extremely low levels of most of the minor amino acids in their source leaves at the end of the night. Illumination led to a decrease in glutamate and an increase in the minor amino acids. A single short day/long night cycle led to an increase in glutamate, and a large decrease in the minor acids at the end of the dark period, and reillumination led to a decrease in glutamate and an increase in the minor amino acids. It is proposed that sugar-mediated control of Nia expression and NR activity overrides regulation by nitrogenous compounds when sugars are in short supply, resulting in a severe inhibition of nitrate assimilation. It is also proposed that su

Amino Acids↗

Dissolution of multicomponent microbubbles in the bloodstream: 2. Experiment.

The effect of the nature of the filling gas on the persistence of microbubbles in the bloodstream was studied. All the microbubbles were covered with the same shells. Various perfluorocarbons and perfluoropolyethers alone and as mixtures with nitrogen were used as the filling gases. The persistence time of microbubbles in the bloodstream tau increased with the molecular weight of the filling gas, from approximately 2 min for perfluorethane, to > 40 min for perfluorodiglyme, C6F14O3, and then decreased again to 8 min for C6F14O5. An acceptable ultrasound scattering efficacy was exhibited by the filling gases with intermediate molecular weights that possessed both a high saturated vapor pressure and a comparatively low water solubility (Ostwald coefficient). On the basis of the experimental data, it is concluded that the microbubble persistence tau is controlled primarily by the dissolution of microbubbles and not by the removal of the microbubbles by the reticular endothelial system. Although the qualitative experimental trends are in good agreement with the theoretical model developed previously, there are some quantitative differences. Possible reasons for these differences are discussed.

Air↗

Dissolution of multicomponent microbubbles in the bloodstream: 1. Theory.

The problem of dissolution of a bubble in the bloodstream is examined. The bubble is assumed to be filled with a mixture of a sparingly water-soluble gas (osmotic agent) and air. The dissolution of the bubble has three definite stages. In Stage 1, the bubble quickly swells in air. The swelling ratio depends on the surface tension, blood pressure, level of oxygen metabolism and initial mole fraction of osmotic agent in the bubble. In Stage 2, the osmotic agent slowly diffuses out of the bubble. The squared radius decreases nearly linearly with time, at a rate proportional to the Ostwald coefficient and diffusivity of the osmotic agent. In Stage 3, the partial pressure of the osmotic agent becomes so high that it condenses into a liquid. In order to prolong the lifetime of 5-micron bubbles in the bloodstream from < 1 s (as found with pure air), the osmotic agent must have a low Ostwald coefficient (< or = 10(-4)) and a relatively high saturated vapor pressure at body temperature (> or = 0.3 atm = 3 x 10(4) Pa).

Air↗

First report on the identification of microcystin in a water bloom collected in Belgium.

A toxic cyanobacterial bloom dominated by Microcystis aeruginosa occurred in 1995 in three adjacent ponds near Liège (Belgium) where at the same time conspicuous bird deaths were observed. The toxicity assay using primary rat hepatocytes indicated a high hepatoxicity. A 4 h incubation yielded a LD50 of 0.23 mg bloom material (dry weight)/ml cell culture medium. Toxicity was due to hepatotoxins of the microcystin class, microcystin-LR and-RR being the major microcystins present as determined by RP-HPLC absorption spectra, 1H NMR, and ESMS spectra. Additionally, the bloom sample contained small amounts of microcystin-YR. The microcystin content of the dry bloom biomass was 870 micrograms/g (on the basis of the hepatotoxicity assay) and 556 micrograms/g (on the basis of the RP-HPLC peak area). A higher yield of microcystins was obtained by acetic acid extraction instead of methanol extraction, whereas different extraction temperatures (20 degrees C, 40 degrees C) had no effect on the yield.

Animals↗

Association of copper to metallothionein in hepatic lysosomes of Long-Evans cinnamon (LEC) rats during the development of hepatitis [se e comments].

BACKGROUND: The Long-Evans cinnamon (LEC) rat has a mutation homologous to the human Wilson's disease gene, leading to copper-induced hepatotoxicity. The mechanism of how excess copper damages the liver or what chemical form of copper is toxic is still unclear. RESULTS: In liver cytosol, copper levels were highest just before the onset of hepatitis and declined thereafter. In cytosol, total copper was bound to metallothionein (MT). Considerable amounts of both copper and iron accumulated in lysosomes with increasing age and development of liver damage. Lysosomal levels of presumably reactive non-MT-bound copper were increased. In severely affected livers, large amounts of copper were associated with insoluble material of high density which, upon ultrastructural information, was found to be derived from the lysosomes of Kupffer cells. This copper-rich material is considered to consist of polymeric degradation products of copper-MT. CONCLUSION: We suggest that chronic copper toxicity in LEC rats involves the uptake of copper-loaded MT into lysosomes, where it is incompletely degraded and polymerizes to an insoluble material containing reactive copper. This copper, together with iron, initiates lysosomal lipid peroxidation, leading to hepatocyte necrosis. Subsequent to phagocytosis by Kupffer cells, the reactive copper may amplify liver damage either directly or through stimulation of these cells.

Animals↗

Continuous quality improvement, total quality management, and reengineering: one hospital's continuous quality improvement journey.

In recent years, there has been significantly increasing interest in the application of continuous quality improvement (CQI) and total quality management (TQM) in the health care arena. This case analysis is designed to identify and assess the strategies and processes that led to the successful implementation of CQI in the Emergency Care Center at St. Mary's Hospital in Grand Rapids, MI.

Admitting Department, Hospital↗

Signal-enhancing switched protocols to study higher-order cognitive tasks with PET.

UNLABELLED: We tested the effectiveness of a switched protocol when it is used to detect signals that result from the study of a higher-order cognitive task with PET. Using language tasks that have been studied extensively in our laboratories, we compared the signal-to-noise ratio (S/N) and statistical significance of the activation signals detected in PET images of regional cerebral blood flow (rCBF), obtained using a standard activation protocol, and of activity concentration, obtained using a switched protocol. METHODS: Four volunteers were studied with PET while they were performing synonym-generation and word-repetition tasks (activation and baseline tasks, respectively). Each volunteer had three activation/baseline and three baseline/ activation scans. Data for each scan were collected in two frames (60 and 120 sec long). During the first 60 sec, data were collected using a standard activation protocol. Subjects then switched tasks, and acquisition continued for 120 sec. Two images were obtained from each scan: an rCBF image using the first frame and an activity-concentration image using both frames. Images were transformed into Talairach space, subtracted and averaged within and across subjects. Parametric t-statistic images were generated for each protocol, and the magnitude and significance of the activation signals yielded by the two acquisition methods were compared. RESULTS: All the activation foci detected using measurements of rCBF were detected when the switched protocol was used; this protocol, in addition, yielded better S/N values. The cognitive component introduced by task-switching in switched protocols did not yield extra statistically significant foci. In single subjects, the average improvement in the signal significance from regions of activation, at a 95% confidence level, was between 6% and 25%. When scans were averaged across subjects, the switched protocol yielded improvements in signal statistical significance of up to 38%. CONCLUSION: We present evidence suggesting that switched protocols can be used to study higher-order cognitive tasks and that they yield activation foci with S/N values that are greater than those of equivalent foci detected using an rCBF protocol. Switched protocols appear to be easy to apply to the testing of higher-order cognitive functions. However, the extra cognitive requirement of switching tasks during data acquisition may be a limiting factor when switched protocols are used to study memory processes.

Adult↗

Alcohol and drug CAGE screeners for pregnant, low-income women: the California Perinatal Needs Assessment.

The purpose of this study is to evaluate a revised CAGE and a new drug version of the CAGE as screeners for risk of heavier or problem alcohol and/or drug use among a population of low-income, pregnant women and adolescents (n = 1147) recruited from 19 agencies in two California counties. Two versions of the CAGE were used in this analysis: (1) the 4-item Alcohol CAGE, using the year before knowing about pregnancy as the timeframe (as opposed to lifetime prevalence), and (2) a newly developed 4-item Drug CAGE using the same timeframe. The two instruments were assessed on sensitivity, specificity, and area under the receiver operating characteristic curve by using self-reported periconceptional heavier or problem alcohol and drug use as the criteria for the 12 months before knowing about the pregnancy. The results indicate that, for the Alcohol CAGE, the cut-point of 1 yielded the highest sensitivity, while maximizing sensitivity and specificity (receiver operating characteristic analysis) for this sample. For heavier drug use, the Drug CAGE had a high sensitivity rate with a cut-point of 3. The Drug CAGE was not a useful screener for periconceptional lighter drug and marijuana use. These results demonstrate the utility of a revised version of the Alcohol CAGE that incorporates a more specific timeframe (the year before pregnancy) to screen pregnant, low-income women for at-risk heavier or problem alcohol use. The Drug CAGE, which uses the same timeframe, seems to be an effective tool for identifying pregnant, low-income women at risk for heavier drug use only. More psychometric works needs to be done to refine the Drug CAGE for detecting at-risk use of lighter drugs and marijuana.

Adolescent↗

Obligatory role of the LIFG in synonym generation: evidence from PET and cortical stimulation.

We report results from a patient in whom we obtained converging evidence from positron emission tomography (PET) and intraoperative stimulation mapping to support a one-way dissociation between the functional areas involved in word repetition and synonym generation. Intraoperative stimulation mapping interfered with synonym generation but did not disturb word repetition at the same left inferior frontal site at which a cerebral blood flow (CBF) increase had been observed for a synonym generation task. The results for this single subject suggest that the functional areas involved in different aspects of linguistic processing are dissociable and that specific disruption under conditions of cortical stimulation can be correlated with the brain regions identified via PET as the most active during performance of a specific task.

Adult↗