PubMed HealthSearch

Biomedical subjects

M Waterman

Publications and source records attributed to M Waterman.

16 recordsLinked to original sources

Utilization of a clinical pathway in the care of the ambulatory cataract surgical patient.

Rapid changes are occurring in healthcare today. Both customers and consumers of healthcare are demanding a change in the way business is being conducted. According to Smith (1993), healthcare organizations are being prompted to explore and implement systems which will enhance quality care as well as promote cost effective resource utilization. A notable change in recent years is the shift of ophthalmic surgical patients from inpatient to an ambulatory setting. This paper will focus on the implementation of a case management model for ophthalmic patients utilizing clinical pathways on an ambulatory unit. Emphasis will be on the provision of quality care resulting in positive patient outcomes.

Ambulatory Surgical Procedures

Estimating statistical significance of sequence alignments.

Algorithms that compare two proteins or DNA sequences and produce an alignment of the best matching segments are widely used in molecular biology. These algorithms produce scores that when comparing random sequences of length n grow proportional to n or to log(n) depending on the algorithm parameters. The Azuma-Hoeffding inequality gives an upper bound on the probability of large deviations of the score from its mean in the linear case. Poisson approximation can be applied in the logarithmic case.

Algorithms

Regulation of expression of the CYP11A (P450scc) gene in bovine ovarian luteal cells by forskolin and phorbol esters.

This study examines the transcriptional regulation of the bovine CYP11A (P450scc) gene by activators of protein kinase A and protein kinase C in bovine ovarian luteal cells. Cells were transfected with reporter gene constructs containing deletion mutations of the 5'-flanking region of the bovine CYP11A gene linked to the minimal beta-globin gene. A construct containing -118/-101 base pairs of CYP11A sequence retains the same degree of stimulation by forskolin and inhibition by co-treatment with phorbol 12-myristate 13-acetate as larger constructs. This sequence contains two putative binding sites for nuclear proteins, an AP1-like sequence and an overlapping GA box element. Gel shift analysis using nuclear extracts of bovine ovarian luteal cells demonstrated that both the wild-type -118/-101-base pair sequence and a consensus GC box bound Sp1 or Sp1-like proteins. Mutation of the GA box element completely suppressed stimulation by forskolin. Absence of binding using the same mutated sequence correlated with the reporter gene transcription results. Mutation of the AP1-like site had little effect on forskolin induction of phorbol 12-myristate 13-acetate inhibition. These results indicate that both stimulation by forskolin and inhibition by phorbol esters are mediated by the same GA box element, which binds Sp1 or an Sp1-like protein.

Animals

Structure and expression of the human trithorax-like gene 1 involved in acute leukemias.

The human trithorax-like gene 1 (Htrx1 gene) is disrupted in 11q23 translocations that are associated with acute leukemias. Sequencing of a partial human cDNA revealed an open reading frame encoding 1012 amino acids with extensive homology to the Drosophila trithorax protein, particularly in the zinc finger-like domains. Htrx1 gene appears to be unique in the human genome and has been conserved during evolution. Use of the human cDNA as a probe demonstrates that this gene is interrupted in both infant and adult acute myeloid (AML) and lymphoid (ALL) leukemia patients with 11q23 translocations. The structure of the Htrx1 gene around the breakpoints shows that this part of the human gene is interrupted by nine introns. As a result of the rearrangement, zinc finger domains are translocated in both ALL and AML patients. Expression studies reveal that the Htrx1 gene differentially expresses three transcripts within the normal lymphocyte cell lineage.

Acute Disease

Regulation of expression of the genes encoding steroidogenic enzymes.

In recent years it has become apparent that tropic hormones involved in steroidogenesis act to regulate the expression of the enzymes involved in the various steroidogenic pathways. This is particularly evident in the ovary where the episodic secretion of steroids throughout the ovarian cycle is regulated largely by changes in the levels of the particular enzymes involved in each step of the steroid biosynthetic pathways. Recently, the genes for the various cytochrome P450 species involved in ovarian steroidogenesis, namely cholesterol side-chain cleavage P450 (P450SCC), 17 alpha-hydroxylase P450 (P450(17 alpha], and aromatase cytochrome P450 (P450AROM) have been isolated and characterized, making it possible to study the regulation of expression at the molecular level. To this end, a series of chimeric constructs have been prepared in which fragments of the 5'-untranslated region of bovine P450(17 alpha) and P450SCC have been inserted upstream of the chloramphenicol acetyl transferase (CAT) and beta-globin reporter genes. These constructs have been used to transfect primary cultures of bovine luteal and thecal cells. The results indicate that cAMP responsiveness lies within defined regions of genes which do not contain a classical CRE, similar to previous results utilizing adrenal cells in culture. Furthermore, although constructs containing both the P450(17 alpha) and P450SCC 5'-upstream regions are expressed in both luteal and thecal cell cultures, only those containing the P450SCC sequences are expressed in luteal cells. Studies on the expression of P450AROM indicate that the promoter which is responsible for its expression in human placenta is not operative in the corpus luteum. Thus estrogen biosynthesis may be regulated by the differential use of tissue specific promoters, thus accounting for the complexity and multifactorial nature of the expression of this activity.

Animals

Optimizing restriction fragment fingerprinting methods for ordering large genomic libraries.

We present a statistical analysis of the problem of ordering large genomic cloned libraries through overlap detection based on restriction fingerprinting. Such ordering projects involve a large investment of effort involving many repetitious experiments. Our primary purpose here is to provide methods of maximizing the efficiency of such efforts. To this end, we adopt a statistical approach that uses the likelihood ratio as a statistic to detect overlap. The main advantages of this approach are that (1) it allows the relatively straightforward incorporation of the observed statistical properties of the data; (2) it permits the efficiency of a particular experimental method for detecting overlap to be quantitatively defined so that alternative experimental designs may be compared and optimized; and (3) it yields a direct estimate of the probability that any two library members overlap. This estimate is a critical tool for the accurate, automatic assembly of overlapping sets of fragments into islands called "contigs." These contigs must subsequently be connected by other methods to provide an ordered set of overlapping fragments covering the entire genome.

Genomic Library

Neurosteroids: cytochrome P-450scc in rat brain.

The steroid hormones corticosterone and testosterone are supplied to the central nervous system by endocrine glands, the adrenals and gonads. In contrast, the 3 beta-hydroxy-delta 5-derivatives of cholesterol, pregnenolone and dehydroepiandrosterone, accumulate in the rat brain through mechanisms independent of peripheral sources. Immunohistochemical studies have been performed with specific antibodies to bovine adrenal cytochrome P-450scc, which is involved in cholesterol side-chain cleavage and pregnenolone formation. The enzyme was localized in the white matter throughout the brain. Scarce clusters of cell bodies were also stained in the entorhinal and cingulate cortex and in the olfactory bulb. These observations strongly support the existence of "neurosteroids," which have been posited on the basis of biochemical, physiological, and behavioral studies.

Adrenal Glands

Molecular mechanisms of phorbol ester, thyrotropin-releasing hormone, and growth factor stimulation of prolactin gene transcription.

The polypeptide thyrotropin-releasing hormone (TRH) and epidermal growth factor (EGF) stimulate, within seconds to minutes, the transcription of the prolactin gene in a rat pituitary cell line (GH4). Because a series of agents that act to stimulate prolactin secretion fail to alter prolactin gene transcription, it is suggested that secretory events are neither obligatory for nor causal of hormone-induced transcriptional stimulation. Elevation of cytosolic-free calcium does not stimulate prolactin gene transcription; however, several agents that act to antagonize calcium-dependent processes inhibit or abolish both TRH and EGF stimulation of prolactin gene transcription and a specific hormone-dependent nuclear phosphorylation. In contrast, inhibitors of the slow calcium channel exert minimal effects on TRH-stimulated prolactin gene expression, suggesting that calcium influx through membrane channels is not crucial for the observed nuclear actions of TRH. Activation of protein kinase C by phorbol esters mimics the nuclear actions of TRH. In the presence of increased intracellular calcium levels, the effects of 12-O-tetradecanoyl phorbol 13-acetate on prolactin gene transcription are quantitatively identical to those observed in response to TRH or EGF.

Animals

Cyclic AMP regulation of eukaryotic gene transcription by two discrete molecular mechanisms.

In experiments designed to study the mechanism by which peptide hormones binding to their plasma membrane receptors stimulate the expression of specific genes, the transcription of two neuroendocrine genes, prolactin and growth hormone, was analyzed in a rat pituitary cell line. The results showed that cyclic adenosine monophosphate (cyclic AMP) stimulates the transcription of discrete subsets of eukaryotic genes by at least two independent molecular mechanisms. Cyclic AMP stimulated growth hormone gene transcription and phosphorylation of a 19,000-dalton nuclear protein; this appears to reflect direct nuclear actions of the cyclic AMP-dependent protein kinase. In contrast, the stimulation by cyclic AMP of prolactin gene transcription appears to reflect activation of a discrete calcium-dependent event.

Animals

Detection of myoglobin by radioimmmunoassay in human sera: its usefulness and limitations as an emergency room screening test for acute myocardial infarction.

The results indicate that serum myoglobin determinations may be obtained by radioimmunoassay utilizing time periods for the testing which allow more useful clinical evaluation of patients. The data also demonstrate, however, that there are important temporal considerations in using serum myoglobin levels for the detection of acute myocardial infarcts and, if this test is used to determine in the Emergency Room whether patients have had acute myocardial infarcts, these limitations will have to be kept in mind. In addition, three other patient subgroups that might be expected to have elevated serum myoglobin levels by radioimmunoassay have been determined. These include patients with shock (irrespective of etiology), patients with severe renal insufficiency, i.e., those with serum creatinine levels equal to or greater than 8 mg. per cent, and possibly patients who have been on alcohol binges immediately prior to being seen in the Emergency Room.

Acute Disease

E.s.r. radiation studies of erythrocyte membrane haemoglobin interaction.

The dependence of the yield of free radicals in gamma-irradiated, freeze-dried erythrocyte membranes on their haemoglobin content was studied. A non-monotonous relationship was found--different from that observed in mixtures of freeze-dried membranes and haemoglobin, which suggests the existence of radiation-energy transfer between the membranes and bound haemoglobin.

Electron Spin Resonance Spectroscopy