Biomedical subjects

C M Zimmerman

Publications and source records attributed to C M Zimmerman.

6 recordsLinked to original sources

PubMed2001

Cost of diarrhea-associated hospitalizations and outpatient visits in an insured population of young children in the United States.

OBJECTIVE: To assess the financial and clinical burden of diarrhea- and rotavirus-associated disease among a population of privately insured US children. METHODS: For the period 1993 through 1996, we analyzed medical claims data from a large, administrative database containing information on approximately 300,000 children <5 years of age to examine trends in, and costs associated, with hospitalizations and outpatient visits for diarrhea. RESULTS: An annual average of 1,186 diarrhea-associated hospitalizations (35 per 10,000 children <5 years) and 33 386 outpatient visits (943 per 10,000 children <5 years) were reported, accounting for 4% of all hospitalizations and 2% of all outpatient visits among children <5 years of age. Diarrhea-associated hospitalizations and outpatient visits showed a distinct winter-spring peak consistent with that of rotavirus infection. The excess of diarrhea-associated events occurring during the winter-spring peak accounted for an average of 50% of all diarrhea-associated hospitalizations and 18% of all diarrhea-associated outpatient visits. The median cost (in 1998 constant dollars) of a diarrhea-associated hospitalization was $2,307, and that for a rotavirus-associated hospitalization was $2,303. Median costs of diarrhea- and rotavirus-associated outpatient visits were $47 and $57, respectively. CONCLUSIONS: Diarrhea is an important cause of morbidity in this insured population of young children. The epidemiologic features of diarrhea-associated events suggest that rotavirus is an important contributor to the overall morbidity from diarrhea. These disease burden and cost estimates should provide useful information with which to assess the costs and benefits of future interventions for rotavirus-associated illness.

Child, Preschool↗

PubMed2000

Transforming growth factor beta signaling mediators and modulators.

Transforming growth factor beta is a multi-functional growth and differentiation factor responsible for regulating many diverse biological processes in both vertebrate and invertebrate species. Among the most dramatic of TGFbeta's effects are those associated with specification of cell fates during development and inhibition of cell cycle progression. The core TGFbeta signaling pathway has now been described using a synergistic combination of genetic and biochemical approaches. Transmembrane receptors with intrinsic protein serine kinase activity bind ligand in the extracellular milieu and then phosphorylate intracellular proteins known as Smads. Phosphorylated Smads form heterooligomers and translocate into the nucleus where they can modulate transcriptional responses. More recent studies indicate that many other proteins serve as modulators of Smad activity, and utimately define specific cellular responses to TGFbeta. Here we describe both the simplistic core TGFbeta signaling pathway and the growing number of proteins that impinge on this pathway at the level of Smad function to either enhance or inhibit TGFbeta responses.

Animals↗

PubMed2000

Trends in intussusception-associated hospitalizations and deaths among US infants.

CONTEXT: The newly licensed tetravalent rhesus-human reassortant rotavirus vaccine has been withdrawn following reports of intussusception among vaccinated infants. OBJECTIVE: To describe the epidemiology of intussusception-associated hospitalizations and deaths among US infants. DESIGN: This retrospective cohort study examined hospital discharge data from the National Hospital Discharge Survey for 1988-1997, Indian Health Service (IHS) for 1980-1997, California for 1990-1997, Indiana for 1994-1998, Georgia for 1997-1998, and MarketScan for 1993-1996, and mortality data from the national multiple cause-of-death data for 1979-1997 and linked birth/infant death data for 1995-1997. PATIENTS: Infants (<1 year old) with an International Classification of Diseases, Ninth Revision, Clinical Modification code for intussusception (560.0) listed on their hospital discharge or mortality record, respectively. RESULTS: During 1994-1996, annual rates for intussusception-associated infant hospitalization varied among the data sets, being lowest for the IHS (18 per 100 000; 95% confidence interval [CI] = 9-35 per 100 000) and greatest for the National Hospital Discharge Survey (56 per 100 000; 95% CI = 33-79 per 100 000) data sets. Rates among IHS infants declined from 87 per 100 000 during 1980-1982 to 12 per 100 000 during 1995-1997 (relative risk =7.6, 95% CI = 3.2-18.2). Intussusception-associated hospitalizations were uncommon in the first 2 months of life, peaked from 5 to 7 months old, and showed no consistent seasonality. Intussusception-associated infant mortality rates declined from 6.4 per 1 000 000 live births during 1979-1981 to 2.3 per 1 000 000 live births during 1995-1997 (relative risk = 2.8, 95% CI = 1.8-4.3). Infants whose mothers were <20 years old, nonwhite, unmarried, and had an education level below grade 12 years were at an increased risk for intussusception-associated death. CONCLUSIONS: Intussusception-associated hospitalization rates varied among the data sets and decreased substantially over time in the IHS data. Although intussusception-associated infant deaths in the United States have declined substantially over the past 2 decades, some deaths seem to be related to reduced access to, or delays in seeking, health care and are potentially preventable.intussusception, hospitalizations, deaths, risk factors, infants.

Black People↗

PubMed1998

Smad proteins physically interact with calmodulin.

The Smad family of intracellular proteins mediates signals generated by activin and other transforming growth factor beta-related proteins via specific heteromeric complexes of transmembrane receptor serine kinases (1, 2). xSmad2 has been implicated as an activin signal mediator that may participate in transcriptional regulation (3, 4). We have employed an interaction cloning strategy to identify xSmad2-binding proteins and found that calmodulin directly associated with Smads. xSmad2, generated either by in vitro translation or by overexpression in COS cells, specifically bound to calmodulin-agarose; the association was calcium-dependent and required xSmad2 N-terminal residues. In the same assay, xSmad1 and hSmads 2, 3, and 4 also bound to calmodulin-agarose. Furthermore, a calmodulin antagonist, W13, increased expression of the activin-inducible transcriptional reporter, 3TP-Lux, whereas overexpression of calmodulin suppressed this reporter. These observations demonstrate that Smad proteins interact with calmodulin in a calcium-dependent way through conserved N-terminal amino acids and suggest a role for calmodulin in regulating Smad function.

Activins↗

PubMed1996

Formation and activation by phosphorylation of activin receptor complexes.

Activin is a protein growth and differentiation factor that initiates intracellular events through the activation of a complex of transmembrane protein serine kinases. Two subfamilies of receptor serine kinases, type I and type II, have been identified, and both receptor types may be required to generate a transmembrane signal. Investigation of the interaction between various activin receptors (ActRs) revealed that ActRs I and II could exist in a stable complex and that formation of that complex between transiently overexpressed molecules was not regulated by ligand. Analysis of phosphorylation suggested that activin induced phosphorylation of receptor I, probably at residues within a conserved glycine and serine-rich sequence in the juxtamembrane region referred to as the GS domain. Phosphorylation of the GS domain was dependent upon a functional ActRII. Introduction of an activin type I receptor, ALK4, into the mink lung epithelial cell line, L17, conferred activin responsiveness on those cells. Mutation of specific combinations of serines and threonines in the core sequence of the ALK4 GS domain to alanine rendered that receptor incompetent for signaling. Mutation of the same sets of residues to glutamic acid produced molecules that supported activin signaling but that did not display elevated basal signaling anticipated for a constitutively active receptor. However, mutation of a threonine residue in the carboxy-terminal half of the GS domain, T206, to glutamic acid yielded receptors with constitutive activity. Taken together, these results support a role for phosphorylation of type I ActRs in the generation of a biological signal.

Activin Receptors↗

PubMed1996

Activin receptors: cellular signalling by receptor serine kinases.

Activins are dimeric growth and differentiation factors which signal through a heteromeric complex of receptor serine kinases. Affinity labelling of activin-responsive cells with 125I-labelled activin A reveals activin-binding species of approximately 50 and 75 kDa, known as the type I and type II receptors, respectively. Molecular cloning has yielded genes encoding two type II receptors (ActRII and ActRIIB) and at least two type I receptors (ALK2 and ALK4). These receptors are members of a larger family of receptor serine kinases, which includes receptors for transforming growth factor beta (TGF beta), bone morphogenetic proteins and the Drosophila protein, decapentaplegic. Receptors I and II form a stable complex after ligand binding, resulting in phosphorylation of receptor I by receptor II. We have begun to identify intracellular targets of these molecules by using the intracellular domains of both ActRIs and ActRIIs as probes in the two-hybrid system, a cloning strategy designed to detect interacting proteins in yeast.

Activin Receptors↗