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PubMed1986

Medicare and Medicaid programs; conditions of participation for hospitals--HCFA. Final regulations.

These regulations revise the requirements that hospitals must meet in order to participate in the Medicare and Medicaid programs (Titles XVIII and XIX of the Social Security Act). These revisions are intended to simplify and clarify Federal requirements, to provide maximum flexibility in hospital administration while strengthening patient health and safety, to emphasize outcomes rather than processes, to promote cost effectiveness while maintaining quality care, and to achieve more effective compliance with Federal requirements. These regulations also incorporate conforming changes relating to certification of psychiatric hospitals and participation of tuberculosis hospitals made by the Deficit Reduction Act of 1984 (Pub. L. 98-369).

Centers for Medicare and Medicaid Services, U.S.↗
PubMed2004

Common carp metallothionein-1 gene: cDNA cloning, gene structure and expression studies.

Metallothionein-1 (MT-1) cDNA clones were isolated from a common carp (Cyprinus carpio) uninduced hepatopancreas cDNA library. Northern blot assay using the common carp (cc) MT-1 cDNA as a probe showed high fold induction of ccMT mRNA levels in the intestine and kidney following exposure to Cd2+ and Zn2+. Using polymerase chain reaction (PCR), primers designed from the cDNA sequences allowed the isolation of ccMT-1 gene fragments including the 5'-flanking region. The 600 bp 5'-flanking region of ccMT-1 gene carries four putative metal regulatory regions, one AP1, two SP1, one c-Jun site, and a TATA box. The 5'-flanking region of the ccMT-1 gene obtained was a functional promoter responding to the administration of various metal ions as well as hydrogen peroxide (H2O2) and lipopolysaccharide (LPS). When tested in primary cultures of cc hepatocytes, Zn2+ had the highest fold (20 times) induction of the 600 bp cloned ccMT-1 gene promoter, followed by Cu2+, Hg2+, Ni2+ and Pb2+ (4-5-fold inductions); H2O2 and LPS had a 6-7-fold induction. In conclusion, the ccMT-1 is a constitutively expressed MT and its gene promoter is inducible by various metal ions and chemical agents.

Amino Acid Sequence↗
PubMed2004

Buccal or sublingual misoprostol for cervical ripening and induction of labour.

BACKGROUND: This is one of a series of reviews of cervical ripening and labour induction using standardised methodology. Misoprostol administered by the oral and sublingual routes have the advantage of rapid onset of action, while the sublingual and vaginal routes have the advantage of prolonged activity and greatest bioavailability. OBJECTIVES: To determine the effectiveness and safety of misoprostol administered buccally or sublingually for third trimester cervical ripening and induction of labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (8 December 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), and bibliographies of relevant papers. SELECTION CRITERIA: Randomised controlled trials comparing buccal or sublingual misoprostol used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods. DATA COLLECTION AND ANALYSIS: A generic strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. Data were extracted onto standardized forms, checked for accuracy, and analysed using RevMan software. MAIN RESULTS: Three studies (502 participants) compared buccal/sublingual misoprostol respectively with a vaginal regimen (200 microg versus 50 microg) and with oral administration (50 versus 50 microg and 50 versus 100microg).The buccal route was associated with a trend to fewer caesarean sections than with the vaginal route (18/73 versus 28/79; relative risk (RR) 0.70; 95% confidence interval (CI) 0.42 to 1.15). There were no significant differences in any other outcomes. When the same dosage was used sublingually versus orally, the sublingual route was associated with less failures to achieve vaginal delivery within 24 hours (12/50 versus 19/50; RR 0.63, 95% CI 0.34 to 1.16), reduced oxytocin augmentation (17/50 versus 23/50; RR 0.74, 95% CI 0.45 to 1.21) and reduced caesarean section (8/50 versus 15/50; RR 0.53, 95% CI 0.25 to 1.14), but the differences were not statistically significant. When a smaller dose was used sublingually than orally, there were no differences in any of the outcomes. REVIEWERS' CONCLUSIONS: Based on only three small trials, sublingual misoprostol appears to be at least as effective as when the same dose is administered orally. There are inadequate data to comment on the relative complications and side-effects. Sublingual or buccal misoprostol should not enter clinical use until its safety and optimal dosage have been established by larger trials.

Administration, Oral↗
PubMed1979

Behavioral toxicology of carbon disulfide and toluene.

Organic solvents are pervasive in the communal and industrial environments. Although many are potent central nervous system agents, clearly delineated behavioral effects have played only a minor role in the formation of exposure standards. A comprehensive behavioral pharmacology and toxicology of these compounds is one aim of US/USSR collaboration. The current report describes some actions of carbon disulfide and toulene. Earlier data about the actions of carbon disulfide on pigeon operant performance indicated disruption of schedule-controlled key-pecking. Primate data are now described from a situation designed to determine aversive thresholds to electrical stimulation. Effective concentrations of carbon disulfide produced both a rise in the amount of electric shock tolerated and a diminution of the response force exerted by the monkeys. In experiments with toluene, pigeons were shown to elevate key-pecking rate in an operant situation at certain concentrations. Toluene also was studied for its capacity to maintain self-administration in the same way as drugs of abuse. Monkeys worked to gain access to toulene vapor just as they work for opiates or amphetamines. The current experiments demonstrate how comprehensive the range of behavioral toxicology needs to be to deal with environmental health issues.

Animals↗
PubMed1995

Oxytocin and the molecular basis of monogamy.

Previous studies in rats have implicated central oxytocin (OT) pathways in the onset of maternal behavior, female sexual receptivity, and the response of the pups to social separation. However, the rat is not ideal for studying effects of OT on attachment as rats fail to form selective, enduring social bonds. To study male-female pair bonds, our laboratory has focused on a microtine rodent, the prairie vole, which is monogamous and highly affiliative. Adult prairie voles form pair bonds after mating (with prolonged, repeated bouts of copulation). As mating releases OT in several species of mammals, we hypothesized that this release was important for pair bond formation in the prairie vole. Central administration of an OT antagonist (but not a V1 antagonist) prevents pair bonding without interfering with the mating behavior. Moreover, central infusion of OT (but not vasopressin, AVP) facilitates pair bonding n the absence of mating. In males, it is AVP (not OT) that appears necessary for pair bond formation. The pattern of OT (and AVP) receptor distribution in the prairie vole brain is entirely distinct from the pattern observed in the closely related non-monogamous montane vole. OT receptors (OTR) in these two species show virtually identical kinetics, specificities, and cDNA sequences (RNA from parturient uterus). In current studies, we are screening genomic libraries from prairie and montane voles to determine if species differences in OTR promoters account for the strikingly different patterns of regional expression in brain. These studies should ultimately provide insight into a neuroendocrine mechanism for pair bond formation.

Animals↗
PubMed2004

Wide range of socioeconomic factors associated with mortality among cities in Japan.

The aim of this study was to identify socioeconomic factors associated with mortality among cities in Japan. Sex-specific and age-adjusted mortality rates for 1990 and 1995 were calculated by 779 local administrative units across the nation. One hundred indicators related to socioeconomic factors were compiled and divided into eight categories: economy, education, living conditions, vegetation and open space, transport, preventive activities, medical care and demography. Composite socioeconomic indices were formulated using factor analysis of the socioeconomic indicators by category, and the association between the indices and mortality rates was examined by correlation analysis and multiple regression analysis. Nineteen composite socioeconomic indices were obtained from factor analysis, and all indices except educational expenditure-related index were significantly correlated with mortality rates. Unemployment, old housing, primary health resources and density were independently positively associated, and higher education, public library activity, health check-up participation and population growth were independently negatively associated with both 1990 and 1995 male mortality rates. For female mortality, higher income, unemployment, spacious dwelling, old housing, less vegetation, road facility, numbers of cars per population, primary health resources and density were independently positively associated, and higher education, public library activity and health check-up participation were independently negatively associated. The relationship between mortality and socioeconomic conditions was stronger in males than in females, and higher income and less vegetation were associated with higher mortality only for females. The present study demonstrated a close link between mortality and a wide range of socioeconomic conditions by using a number of indicators compiled from various data sources. The results promote a deeper understanding of socioeconomic health determinants and development of multi-sectoral health policy to improve population health.

Adult↗
PubMed2006

Attenuation of skeletal muscle reperfusion injury with intravenous 12 amino acid peptides that bind to pathogenic IgM.

BACKGROUND: The injury sustained by reperfused skeletal muscle is inflammatory and is initiated by binding of pre-formed IgM to involved tissue, followed by local complement activation and further inflammation. A clone of natural IgM has been described that initiates this injury, suggesting that specific antigens are exposed on ischemic tissues that act as ligands for this pathogenic antibody. In these experiments, we examine the properties of short peptide sequences, and their homologues, that bind to the antigen-combining site of this pathogenic IgM clone. METHODS: A 12-mer phage display library was biopanned with the pathogenic IgM clone and then negatively selected against an inactive natural IgM clone. All 8 clones that bound specifically to the pathogenic IgM had closely related amino acid sequences. P8 is the clone that bound most avidly. Tissue lysates from ischemic tissue were reacted with pathogenic IgM, and immune complexes isolated and analyzed on SDS-PAGE. Bands were excised and sequenced, identifying non-muscle myosin as the protein reacting with pathogenic antibody in ischemic gut and glycogen phosphorylase as the counterpart in ischemic skeletal muscle. Both proteins contain sequence homologous to P8; N2 and GP1 are the natural 12-mers homologues that are contained within non-muscle myosin and glycogen phosphorylase, respectively. Wild-type C57/Bl6 mice, divided into groups receiving saline, P8, N2, GP1, or a random peptide at the start of the experiment, were subjected to 2 hours of tourniquet induced hind limb ischemia and 3 hours of reperfusion. Muscle was assessed for injury with histology and for immune activation with histochemistry. RESULTS: Intravenous administration of P8, N2, and GP1 led to significant attenuation of muscle injury (13 +/- 1.8 injured fibers/50 counted, 12 +/- 0.81, 8.0 +/- 0.73 respectively) after reperfusion injury compared to animals receiving saline (26 +/- 2.3) or the same mass of a random peptide (22 +/- 2.3), P less than .05. This level of protection from injury is comparable to that seen in the absence of antibody altogether. As well, P8-treated animals exhibited a marked decrease in deposition of IgM (as well as C3) in comparison to saline treated controls. CONCLUSIONS: Specific peptide blockade of an injury-inducing IgM clone decreased the local consequences of skeletal muscle ischemia/reperfusion injury in wild-type animals that have the full repertoire of IgM specificities. This indicates that the antibodies that initiate reperfusion injury have specificity only for P8-related antigens. This could also indicate that the variety of relevant ischemic antigens is quite restricted.

Animals↗
PubMed1991

Journals indexed by the AHA Resource Center for Hospital Literature Index and HEALTH database.

The American Hospital Association (AHA) Resource Center indexes journals for the Health Planning and Administration (HEALTH) database and Hospital Literature Index (HLI). These journals, designated special list health journals, are selected to provide access to a wide and balanced coverage of hospital and health care administration and health policy literature. This article provides background information on HEALTH and HLI and describes special list health journals in detail (including historical information, information sources, and broad subject divisions). It also discusses AHA policies relating to journal and article selection and current subject distribution of special list health journals.

Abstracting and Indexing↗
PubMed2004

The selection and use of essential medicines.

This report presents the recommendations of the WHO Expert Committee responsible for updating the WHO Model List of Essential Medicines. The first part contains a progress report on the new procedures for updating the Model List and the development of the WHO Essential Medicines Library. It continues to present a summary of the Committee's considerations and justifications for additions and changes to the Model List, including its recommendations. Annexes to the main report include the revised version of the WHO Model List of Essential Medicines (the 13th) and a list of all items on the Model List sorted according to their 5-level Anatomical Therapeutic Chemical (ATC) classification codes.

Advisory Committees↗
PubMed2005

Analgesia and local anesthesia during invasive procedures in the neonate.

BACKGROUND: Preterm and full-term neonates admitted to the neonatal intensive care unit or elsewhere in the hospital are routinely subjected to invasive procedures that can cause acute pain. Despite published data on the complex behavioral, physiologic, and biochemical responses of these neonates and the detrimental short- and long-term clinical outcomes of exposure to repetitive pain, clinical use of pain-control measures in neonates undergoing invasive procedures remains sporadic and suboptimal. As part of the Newborn Drug Development Initiative, the US Food and Drug Administration and the National Institute of Child Health and Human Development invited a group of international experts to form the Neonatal Pain Control Group to review the therapeutic options for pain management associated with the most commonly performed invasive procedures in neonates and to identify research priorities in this area. OBJECTIVE: The goal of this article was to review and synthesize the published clinical evidence for the management of pain caused by invasive procedures in preterm and full-term neonates. METHODS: Clinical studies examining various therapies for procedural pain in neonates were identified by searches of MEDLINE (1980-2004), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2004), the reference lists of review articles, and personal files. The search terms included specific drug names, infant-newborn, infant-preterm, and pain, using the explode function for each key word. The English-language literature was reviewed, and case reports and small case series were discarded. RESULTS: The most commonly performed invasive procedures in neonates included heel lancing, venipuncture, IV or arterial cannulation, chest tube placement, tracheal intubation or suctioning, lumbar puncture, circumcision, and SC or IM injection. Various drug classes were examined critically, including opioid analgesics, sedative/hypnotic drugs, nonsteroidal anti-inflammatory drugs and acetaminophen, injectable and topical local anesthetics, and sucrose. Research considerations related to each drug category were identified, potential obstacles to the systematic study of these drugs were discussed, and current gaps in knowledge were enumerated to define future research needs. Discussions relating to the optimal design for and ethical constraints on the study of neonatal pain will be published separately. Well-designed clinical trials investigating currently available and new therapies for acute pain in neonates will provide the scientific framework for effective pain management in neonates undergoing invasive procedures.

Analgesia↗
PubMed1990

Characterization of rat transferrin receptor cDNA: the regulation of transferrin receptor mRNA in testes and in Sertoli cells in culture.

A 3.4 kilobase cDNA complementary to rat transferrin receptor mRNA has been isolated from an adult rat testis cDNA library. The rat transferrin receptor nucleotide sequence was shown to be 82% similar to the human transferrin receptor sequence over the amino acid coding region and over 90% similar in the sequences known to be responsible for iron regulation in the human mRNA. The mRNA was shown by Northern blot analysis to be regulated by iron levels in Sertoli cells in culture. Iron depletion resulted in at least a 5-fold increase in receptor message in Sertoli cells, as well as in an actively growing testicular cell line (S10-7). The level of transferrin receptor mRNA in cultured Sertoli cells was not influenced by hormones; however, chronic administration of testosterone or FSH to hypophysectomized rats resulted in increased transferrin receptor mRNA levels in the testis. Northern blot analysis of mRNAs from testes of rats synchronized at various stages of the cycle of the seminiferous epithelium showed that transferrin receptor mRNA was differentially regulated throughout the cycle. Northern blots of mRNA from germinal cell populations derived from synchronized tests showed that the message was regulated in the nongerminal cell components of the tubule, most likely the Sertoli cell. The comparison of transferrin receptor mRNA levels in normal testes and testes from hypophysectomized rats, as well as in isolated germinal cells and cultured Sertoli cells, suggested that transferrin receptor mRNA levels were considerably higher in Sertoli cells than in other cell types of the seminiferous tubules.

Amino Acid Sequence↗
PubMed1987

Isolation, complementary DNA sequence, and regulation of rat hepatic lauric acid omega-hydroxylase (cytochrome P-450LA omega). Identification of a new cytochrome P-450 gene family.

Lauric acid omega-hydroxylase (cytochrome P-450LA omega) was purified from livers of rats that had been given the hypolipidemic drug clofibrate. Immunoblot analysis with anti-cytochrome P-450LA omega antibody revealed the presence of two clofibrate-induced cytochrome P-450 proteins in both liver and kidney. This antibody was used to screen a lambda gt11 expression library constructed from liver mRNA isolated from rats given clofibrate. The clone, pP-450LA omega, was isolated and found to contain 2062 base pairs with an open reading frame of 509 amino acids (Mr 58,222). The pP-450LA omega cDNA insert was placed in the yeast expression vector pAAH5, and the resultant plasmid expressed a protein of the same size and activity as cytochrome P-450LA omega. The mechanism of the regulation of the cytochrome P-450LA omega gene by hypolipidemic agents was examined. The rate of cytochrome P-450LA omega gene transcription was increased as early as 1 h after administration of clofibrate, and this increase was followed by an elevation of cytochrome P-450LA omega mRNA, immunochemically detectable protein, and cytochrome P-450LA omega activity. In contrast, no increase in transcriptional activity was detected after clofibrate administration for the cytochrome P-450PCN or P-450b/e genes. The cytochrome P-450LA omega has several structural features in common with other cytochrome P-450s, including a conserved cysteine-containing heme-binding fifth ligand fragment and a hydrophobic amino terminus. Overall, cytochrome P-450LA omega shared less than 35% cDNA nucleotide and amino acid similarity with cytochromes P-450c, P-450d, P-450e, and P-450PCN, indicating that it is a member of a new cytochrome P-450 gene family. Southern blot analysis indicates that this family contains two or three genes.

Amino Acid Sequence↗
PubMed2000

Development and assessment of a radiology core curriculum in health care policy and practice.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the feasibility of implementing a core curriculum in health policy and practice for radiology residents and fellows, to determine whether such a curriculum would be considered professionally valuable by participants, and to determine if the curriculum would influence participants' careers. MATERIALS AND METHODS: A core curriculum in health policy and practice was developed, involving 19 seminars presented over 5 weeks. Twelve faculty members presented comprehensive and integrated information relevant to current and future radiology practice. Topic clusters included health care structure and payment, technology and health services, radiology practice management, and career issues. Classroom teaching was supplemented by a course syllabus and resource library. Participants were surveyed following each seminar and at the conclusion of the curriculum. RESULTS: Participants described their baseline knowledge of each topic as weak. As a result of the curriculum, self-described knowledge ratings increased considerably. Interest in curriculum topics and perception of their importance and relevance to radiology practice increased. Of respondents, 84% (26 of 31) described the curriculum as having very good or excellent educational value. All respondents indicated that the curriculum should be repeated in the future, 42% (13 of 31) indicated that the curriculum motivated them to pursue further related education, and 61% (19 of 31) developed interest in personal involvement in administrative issues and radiology organizations. CONCLUSION: A core curriculum in health policy and practice was successfully integrated into radiology training. The curriculum resulted in increased knowledge, interest, and perceived importance of medical management issues by residents and fellows and stimulated their interest in pursuing further management education and involvement in radiology administration and organizations.

Attitude of Health Personnel↗
PubMed2005

Best practice recommendations for surgical care in weight loss surgery.

OBJECTIVE: To establish evidence-based guidelines for best practices for surgical care in weight loss surgery (WLS). RESEARCH METHODS AND PROCEDURES: We carried out a systematic search of English-language literature on WLS in MEDLINE and the Cochrane Library. Key words were used to narrow the field for a selective review of abstracts. Data extraction was performed, and evidence categories were assigned according to a grading system based on established evidence-based models. RESULTS: We assessed types of WLS, recommended guidelines for appropriateness, developed strategies for medical error reduction, established criteria for credentialing of systems and practitioners, and specified research needed for the future. DISCUSSION: Surgeon training, credentialing, and type of surgery performed were identified as key factors in patient safety. Other important issues in the delivery of best practice care included appropriate patient selection; use of a multidisciplinary treatment team; facility staffing, equipment, and administrative support; and early recognition and proper management of complications.

Biliopancreatic Diversion↗
PubMed2000

New technologies to prevent and treat contact hypersensitivity responses.

Allergic contact dermatitis is a common inflammatory skin disease caused by T cells that recognize environmental and industrial allergens (i.e., haptens). Langerhans' cells (LC), which are skin-specific and "immature" members of the dendritic cell (DC) family of antigen-presenting cells, play crucial roles in the induction of contact hypersensitivity (CH) responses. Upon exposure to haptens, LC migrate from the epidermis to draining lymph nodes, mature into T cell-stimulatory DC, and activate hapten-reactive T cells. Therefore, CH responses should be preventable at the sensitization phase by interfering with one of these changes that occur in LC. Our objective is to develop new technologies for the prevention and treatment of allergic contact dermatitis. In this article, we will introduce three technologies that we have recently developed. First, using a phage display strategy, we have identified a 12-mer peptide (termed "peptide 1") that binds and blocks the function of hyaluronan (HA), which is known to serve as an adhesive substrate for LC migration. Local injection of peptide 1 in mice before topical application of DNFB blocked almost completely the emigration of LC from the epidermis to the draining lymph node, where antigen presentation takes place. Peptide 1 represents a new strategy that is designed to inhibit the initial event of CH. Second, we have established an in vitro experimental system to study the terminal maturation of LC during antigen-specific interaction with T cells. This experimental system, which employs a long-term LC line and T cell clones, should provide a unique tool for the identification of new immunosuppressive agents that block LC terminal maturation selectively. Finally, under the hypothesis that LC, which are engineered to overexpress a death ligand, would deliver apoptotic signals instead of activation signals to T cells, we created a "killer" LC clone by introducing CD95L cDNA into our long-term LC line XS106. In vivo administration of DNFB-pulsed killer LC into mice, either before or after sensitization, resulted in marked suppression of CH responses to DNFB. The killer LC technology represents an entirely new immunosuppressive therapy that is designed to eliminate only the pathogenic T cells.

Animals↗
PubMed1989

Follistatin gene expression in the ovary and extragonadal tissues.

Follistatin is a glycosylated single-chain protein originally isolated from porcine follicular fluid. It specifically inhibits the secretion of FSH from the pituitary. We have now isolated and characterized a cDNA for rat follistatin from the PMSG-stimulated ovarian library. The deduced amino acid sequence of the rat follistatin precursor is highly homologous (greater than 98%) to porcine and human follistatins including potential Asn-glycosylation sites. The genomic clone encoding rat follistatin was also isolated and revealed that the exon and intron organization of the follistatin gene structure is conserved among rat, porcine, and human. Northern analyses in rat tissues demonstrated that the follistatin gene is expressed not only in the ovary but also in the kidney and brain. In the immature rat ovary, the follistatin mRNA level is stimulated by PMSG injection (20 IU/rat), but is not affected by human CG (10 IU/rat) after PMSG administration. In situ hybridization studies revealed that the mRNA level in the ovary was low in primordial follicles, but dramatically increased in the granulosa cells of the growing secondary and tertiary follicles and then decreased in the mature preovulatory follicles. A strong follistatin mRNA signal was observed over the collecting tubules of the outer medulla of the kidney, and a weak to moderate signal was detected in brain. The broad tissue distribution of follistatin mRNA strongly suggests other physiological roles for follistatin besides the inhibition of pituitary FSH release.

Amino Acid Sequence↗
PubMed1995

Molecular cloning and sequence analysis of striped bass (Morone saxatilis) gonadotrophin-I and -II subunits.

Two types of cDNA, each encoding a different beta-subunit of striped bass (Morone saxatilis, Teleostei) gonadotrophins (GTH-I beta and GTH-II beta), as well as the glycoprotein alpha-subunit, were cloned by screening a striped bass pituitary cDNA library. The probes used for screening the library were cloned cDNA fragments, generated by PCR amplification of reverse-transcribed mRNA obtained from two pituitaries. The nucleotide sequences of the alpha-subunit, GTH-I beta and GTH-II beta are 626, 524 and 580 bases long, encoding peptides of 117, 120 and 147 amino acids respectively. Striped bass GTH-I beta and GTH-II beta share a sequence identity of 48% at the nucleic acid level, and 30% at the amino acid level. A cluster analysis of vertebrate pituitary glycoprotein beta-subunits suggests that teleost GTH-II beta is more closely related to tetrapod LH than to FSH. Administration of gonadotrophin-releasing hormone analogue ([D-Ala6,Pro9Net]-LHRH) to juvenile striped resulted in ten-, two- and fivefold increases in the expression of the alpha-subunit, GTH-I beta and GTH-II beta respectively. These results suggest that each of the GTH subunits is differentially regulated, and further corroborate the functional duality of teleost gonadotrophins.

Amino Acid Sequence↗
PubMed1985

Characterization and metabolic regulation of a liver-specific 5.4-kilobase mRNA whose synthesis is transcriptionally induced by carbohydrates and repressed by glucagon and cyclic AMP.

Four clones derived from a carbohydrate-induced rat liver cDNA library were found to hybridize with a 5.4-kilobase mRNA species encoding a 36 kDa protein. This mRNA was abundant in the liver, barely detectable in adipocytes and kidney, and absent from the other tissues tested. In the liver, the mRNA was fully induced by a carbohydrate-rich diet, but was undetectable during both starvation and feeding with a protein-rich or lipid-rich diet. Adrenalectomized, thyroidectomized and diabetic animals did not express the mRNA in their liver when re-fed with the carbohydrate-rich diet. When these animals were given the missing hormone, the amount of hybridizable RNA returned to normal values, but administration of the hormone alone failed to induce mRNA synthesis in starved animals. Both glucagon and its second messenger, cyclic AMP, abolished the induction of the mRNA in re-fed animals. Exogenous insulin, whatever the dose, did not reverse the inhibitory action of glucagon. In an isolated nuclei transcription system, no detectable RNA transcripts were found in starved animals, whereas feeding the animals with the carbohydrate-rich diet led to a maximum rate of gene transcription. Although unidentified, this mRNA proves to be a remarkable marker of dietary and hormonal control of gene expression in vivo. It will provide a useful model for further analysis of the role of cyclic AMP in regulating the transcription of eukaryotic genes.

Animals↗