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C C Case

Publications and source records attributed to C C Case.

17 recordsLinked to original sources
PubMed2004

Characteristics of US adults with the metabolic syndrome and therapeutic implications.

BACKGROUND: The third Adult Treatment Panel (ATP III) of the National Cholesterol Education Program defines clinical criteria for diagnosis of the metabolic syndrome, which increases cardiovascular risk and is a target for therapy. AIM: We analysed the third National Health and Nutrition Examination Survey (NHANES III; 1988-94) to determine how many US adults meet these criteria and are recommended for lipid-modifying drug therapy by ATP III. METHODS: NHANES III data were used to estimate the number of individuals with the metabolic syndrome and the number recommended for treatment by ATP III, based on 1990 census data. RESULTS: An estimated 36.3 million (23%) US adults have the metabolic syndrome. Of these, 84% met the criterion for obesity, 76% for blood pressure, 75% for HDL-C, 74% for triglycerides and 41% for glucose. Most (54%) are in the higher risk categories of ATP III, yet only 39% overall are recommended for drug therapy by ATP III cutpoints; of these, most will achieve LDL-C targets with reductions of 35-40%. Of the 15.3 million individuals with the metabolic syndrome and triglycerides > or = 2.26 mmol/l (200 mg/dl), non-HDL-C is above ATP III recommendations in 11.6 million. CONCLUSIONS: Of the large number of Americans with the metabolic syndrome, ATP III recommends drug therapy for only a minority, because LDL-C typically is not substantially elevated. Instead, high triglycerides and low HDL-C are more common; clinical trial data are needed to determine whether optimal therapy should focus on reductions in LDL-C or on comprehensive improvements to the lipid profile.

Adult↗
PubMed2002

Diabetic ketoacidosis associated with Metabolife: a report of two cases.

AIM: To describe two cases of diabetic ketoacidosis in newly diagnosed type 1- and type-2-diabetic individuals associated with Metabolife-356. METHODS: We report the acute hospitalizations and clinical courses of two individuals with diabetic ketoacidosis taking Metabolife-356. RESULTS: Both patients presented without a previous diagnosis of diabetes mellitus. One patient clinically has type 1 diabetes (positive islet cell antibodies and subnormal pancreatic beta cell function to glucagon stimulation) and is treated with insulin. The second patient, after 5 days of treatment with intravenous insulin of up to 25 units per hour, is now treated with oral medications. Several possible mechanisms may exist, including the increases in catecholamines and in blood glucose after ingestion of the ingredients of these supplements. Recent clinical trial data shows an increase in blood glucose (in non-diabetics) with these supplements despite significant weight loss at 8 weeks, although no association with diabetes mellitus has been shown in these closely monitored studies. CONCLUSIONS: Although no precipitating factor of diabetic ketoacidosis was found in these individuals, the dietary supplement Metabolife cannot be established as a precipitant. However, patients with diabetes should take this supplement only after consultation with their health care provider, as stated on the product label. Most individuals using this supplement meet the current criteria for screening to detect undiagnosed diabetes mellitus and should consider these tests.

Acute Disease↗
PubMed2002

Impact of weight loss on the metabolic syndrome.

AIM: Individuals with the metabolic syndrome (MS), a clustering of risk factors [triglycerides, glucose, high-density lipoprotein cholesterol, blood pressure (BP), abdominal obesity] defined by the National Cholesterol Education Program (NCEP), are at high risk for coronary heart disease and type 2 diabetes mellitus, and may benefit from aggressive lifestyle modification. METHODS: We reviewed 1 year of consecutive patients' charts to determine the prevalence of the MS in obese individuals enrolled in a medically supervised rapid weight loss programme, the correlation of weight change with the components of the MS, and response to diet-induced weight loss. RESULTS: Out of 185 individuals, 125 (68%) met the NCEP definition of the MS. A moderate decrease in weight (6.5%) induced by a very low calorie diet (VLCD) resulted in substantial reductions of systolic (11.1 mmHg) and diastolic (5.8 mmHg) blood pressure (BP), glucose (17 mg/dl), triglycerides (94 mg/dl) and total cholesterol (37 mg/dl) at 4 weeks (all p < 0.001). These improvements were sustained at the end of active weight loss (average 16.7 weeks; total weight loss 15.1%), with further significant reductions in BP and triglycerides. Weight loss was related to the changes in each criterion of the metabolic syndrome. CONCLUSIONS: The MS is prevalent in two-thirds of obese individuals enrolling in a structured weight loss programme. Moderate weight loss with a VLCD markedly improved all aspects of the MS.

Blood Pressure↗
PubMed2002

Vasoactive intestinal polypeptide-secreting tumor (VIPoma) with liver metastases: dramatic and durable symptomatic benefit from hepatic artery embolization, a case report.

Neuroendocrine tumors often manifest an excess production of hormones that create severe metabolic abnormalities resulting in significant patient morbidity, independent of the tumor burden itself. VIPomas are rare neuroendocrine tumors arising from the pancreas and are associated with secretory diarrhea and electrolyte disturbances. We present a patient with VIPoma and hepatic metastases who had greater than 10 loose stools a day for 4 yr since diagnosis, despite debulking surgery, multiple antidiarrheal medications, large doses of octreotide, and targeted radioisotope injections. The patient required several hospitalizations for treatment of dehydration and electrolyte disturbances, despite receiving daily intravenous fluids at home. Hepatic artery embolization (HAE) immediately stopped the patient's diarrhea and provided a return to normal formed stools without any other symptom-support measures. One year after HAE, the patient remains asymptomatic and has returned to a productive life. HAE can be a very effective and durable treatment modality for patients with metastatic VIPomas (or other neuroendocrine tumors) and who are clinically symptomatic from the effects of hormone hypersecretion.

Antidiarrheals↗
PubMed2001

Regulation of an endogenous locus using a panel of designed zinc finger proteins targeted to accessible chromatin regions. Activation of vascular endothelial growth factor A.

We have mapped conserved regions of enhanced DNase I accessibility within the endogenous chromosomal locus of vascular endothelial growth factor A (VEGF-A). Synthetic zinc finger protein (ZFP) transcription factors were designed to target DNA sequences contained within the DNase I-hypersensitive regions. These ZFPs, when fused to either VP16 or p65 transcriptional activation domains, were able to activate expression of the VEGF-A gene as assayed by mRNA accumulation and VEGF-A protein secretion through a range exceeding that induced by hypoxic stress. Importantly, multiple splice variants of VEGF-A mRNA with defined physiological functions were induced by a single engineered ZFP transcription factor. We present evidence for an enhanced activation of VEGF-A gene transcription by ZFP transcription factors fused to VP16 and p65 targeted to two distinct chromosomal sites >500 base pairs upstream or downstream of the transcription start site. Our strategy provides a novel approach for dissecting the requirements for gene regulation at a distance without altering the DNA sequence of the endogenous target locus.

Cell Line, Transformed↗
PubMed2000

Synthetic zinc finger transcription factor action at an endogenous chromosomal site. Activation of the human erythropoietin gene.

We have targeted the activation of an endogenous chromosomal locus including the human erythropoietin gene using synthetic transcription factors. These transcription factors are targeted to particular DNA sequences in the 5'-flanking region of the erythropoietin gene through engineering of a zinc finger DNA binding domain. The DNA binding domain is linked to a VP16 transcriptional activation domain. We find that these synthetic transcription factors invariably activate transiently transfected templates in which sequences within the 5' flank of the erythropoietin gene are fused to a luciferase reporter. The efficiency of activation under these circumstances at a defined site is dependent on DNA binding affinity. In contrast, only a subset of these same zinc finger proteins is able to activate the endogenous chromosomal locus. The activity of these proteins is influenced by their capacity to gain access to their recognition elements within the chromatin infrastructure. Zinc finger transcription factors will provide a powerful tool to probe the determinants of chromatin accessibility and remodeling within endogenous chromosomal loci.

Cells, Cultured↗
PubMed1996

Fetal surgical protocols in Yucatan miniature swine.

Thirty-nine Yucatan miniature swine were used in three fetal surgical experimental protocols. They involved antiarrhythmic administration, pacemaker implantation, and in-utero diagnosis of ventricular septal defect by intraoperative echocardiography. Because of problems encountered with surgical protocols in the initial stages, modifications were made to prevent fetal hypothermia and intraoperative mortality. These modifications included environmental temperature support, staple surgical techniques to reduce operative time, and development of fetal catheters designed to facilitate cannulation of small vessels. Postoperative care protocols were intensive and included antibiotics, analgesics, and supportive care designed to reduce discomfort and prevent abortion and sepsis. Thirty-seven of 39 sows survived the surgical procedures; experiments were performed on 117 fetuses. Twenty-two fetuses died either intraoperatively or postoperatively because of complications related to the experimental protocols. Modification of surgical and postsurgical protocols for these projects demonstrates the feasibility of using miniature swine as a model for fetal surgery, when their use was appropriate for anatomic and physiologic reasons.

Animals↗
PubMed1992

Prediction of hospital discharge in immediate survivors of ventricular fibrillation or asystole.

Survival from ventricular fibrillation and asystole is influenced by variables measured during resuscitation that affect both immediate survival and discharge from hospital. These variables have been used to develop a formula to calculate an individuals chances of immediate survival and hospital discharge. It has allowed this heterogenous group to be subdivided into groups which can be compared both within and between institutions for the purposes of audit and evaluation of resuscitation protocols. This study evaluates the addition of clinical parameters to the prognostic index. One hundred twelve immediate survivors of ventricular fibrillation or asystole were examined immediately after resuscitation and clinical parameters measured and recorded. At the same time parameters previously described were recorded. The increase in the numbers of survivors improved the reliability (area under the receiver operator curve (ROC) improved from 0.79 to 0.83) of the index for predicting hospital discharge. Addition of the clinical variables of conscious state, respiratory state, blood pressure and pulse rate improved the prognostic index further to an ROC area of 0.86. This ensures that the predictive power of the new index is now highly reliable for predicting hospital discharge after successful resuscitation from ventricular fibrillation and asystole.

Aged↗
PubMed1991

Prediction of survival from resuscitation: a prognostic index derived from multivariate logistic model analysis.

Despite advances in resuscitation, the ability to predict survival at cardiac arrests remains unsophisticated. We identified the factors determining outcome of all cardiopulmonary resuscitations performed at our institution over a 4-year period, and used a Cox multivariate regression model to design prognostic indices to assess the probability of successful resuscitation and hospital discharge. Cardiac arrests (710) were studied, and 193 (28%) were successfully resuscitated. The most influential variables, judged by the size and significance of their logistic regression coefficients, were rhythm, resuscitation delay, and age (for successful resuscitation), and rhythm, performance of intubation and defibrillation, defibrillation delay, and age (for survival until discharge). The combination of these in a prognostic index reliably predicted both outcome (area under the receiver operating curve of 0.78), and survival until discharge (area under the curve of 0.80).

Aged↗
PubMed1990

The IS10 transposase mRNA is destabilized during antisense RNA control.

RNA stability is an important component of gene expression, and antisense RNAs have been proposed to alter target RNA stability. We show here that the IS10 transposase mRNA, RNA-IN, is rendered unstable during control by the IS10 antisense RNA, RNA-OUT. Destabilization requires RNA-OUT/RNA-IN pairing and ribonuclease III cleavage. Independent of such cleavage, RNA-OUT is rendered unstable through disruption of its secondary structure. Pairing has no other obvious effects on RNA-IN transcription or stability. Nevertheless, RNA-IN destabilization is not required for antisense control in vivo. In the accompanying paper [Ma,C. and Simons, R.W. (1990) EMBO J., 9, 1267-1274 we show that pairing blocks ribosome binding to RNA-IN. Were it not for control at this level, destabilization would play a more prominent role.

Base Sequence↗
PubMed1990

Radiation doses to the lens of the eye during computerised tomography of the orbit; a comparison of four modern computerised tomography units.

A previous study has looked at the estimated radiation dose to the lens of the eye during CT scanning of the orbit, pituitary fossa and brain with a recently installed GE 9800 Quick CT using a phantom simulating the lens of the eye. In this study the same phantom was used to compare the estimated radiation dose delivered to the lens of the eye by three other newly installed CT units of different manufacture. There was significant variation between the doses measured from the four machines when operated with the parameters commonly used in clinical practice. However, in all cases scanning of the phantom using routine techniques delivered a dose to the simulated lens which was much lower than the threshold dose for cataracts. There is, never-the-less, a potential for delivery of much higher doses.

Humans↗
PubMed1989

The unusual stability of the IS10 anti-sense RNA is critical for its function and is determined by the structure of its stem-domain.

IS10 transposition is regulated by an approximately 70 nt anti-sense RNA, RNA-OUT. RNA-OUT folds into a duplex 'stem-domain' topped by a loosely paired 'loop-domain'. The loop-domain is critical for RNA-RNA pairing per se; pairing initiates by interaction of the RNA-OUT loop with the 5' end of the target mRNA. We show here that RNA-OUT is unusually stable in vivo (half-life 60 min) and that this stability is conferred by specific features of the RNA-OUT stem-domain. One critical feature is stable base-pairing: mutations that disrupt stem pairing destabilize RNA-OUT in vivo and abolish anti-sense control; combinations of mutations that restore pairing also restore both stability and control. We propose that the stem renders RNA-OUT resistant to 3' exoribonucleases. Other features of the stem-domain prevent this essential duplex from being an effective substrate for double-strand nucleases: two single base mutations disrupt antisense control by making RNA-OUT susceptible to RNase III. Mutations in the loop region have little effect on RNA-OUT stability. Implications for IS10 biology and the design of efficient anti-sense RNAs are discussed.

Bacteriophage lambda↗
PubMed1988

Analysis of the promoters and transcripts involved in IS10 anti-sense RNA control.

Genetic analysis of eleven mutations affecting the IS10 promoters, pIN and pOUT, involved in anti-sense RNA control of transposase gene expression, and characterization of the transcripts, reveal that: (i) The transposase message (RNA-IN) and the anti-sense RNA (RNA-OUT) have been unambiguously identified in vivo. (ii) Five mutations affect pIN activity, and establish that pIN is the only IS10 promoter transcribing the tnp gene, and the only such IS10 promoter that responds to DNA-adenine methylation. (iii) Six mutations alter pOUT activity, and establish that pOUT is the only IS10 promoter specifying the anti-sense RNA-OUT. (iv) The latter, however, need not be so: heterologous promoters, if properly positioned, can also specify active anti-sense RNAs. (v) These heterologously promoted anti-sense RNAs are processed to species closely resembling native RNA-OUT.

Bacteriophage lambda↗
PubMed1986

Contrasting mechanisms of envZ control of mal and pho regulon genes in Escherichia coli.

The envZ11 missense mutation in the regulatory gene envZ pleiotropically repressed synthesis of OmpF, alkaline phosphatase, and several proteins of the maltose regulon. Procaine treatment of wild-type cells resulted in the same phenotype through an envZ+-mediated mechanism. Here we show that envZ11-procaine act differently on the mal and pho regulons. In the mal system, the expression of the positive regulator gene malT, measured as beta-galactosidase activity of a malT-lac+ operon fusion, was drastically reduced by procaine treatment or by the envZ11 mutation. In contrast, expression of the positive regulator of the pho regulon phoB was not reduced by procaine treatment. The products of the regulatory genes phoM, phoR, and phoU were also not required for procaine action. Procaine and envZ11 inhibited expression of only two products of the pho regulon, alkaline phosphatase and the PhoE porin. The conclusion that envZ11-procaine act differently on the mal and the pho regulons is supported by our ability to isolate second-site mutations with a Mal+ PhoA- phenotype in an envZ11 strain.

Alkaline Phosphatase↗
PubMed1984

envZ mediates transcriptional control by local anesthetics but is not required for osmoregulation in Escherichia coli.

Expression of a particular set of exported protein genes (ompF, ompC, phoA, and malE) can be specifically altered in three ways: variation in the osmotic strength of the growth medium, mutations in the regulatory locus envZ, or treatment with sublethal concentrations of the local anesthetic procaine. To clarify relationships among these factors in the regulation of transcription, expression of the affected genes was compared in envZ+ and envZ22(Am) mutant strains grown in media of differing osmolarities with and without procaine. Loss of the envZ product resulted in complete resistance of gene expression to procaine, supporting the hypothesis that envZ mediates procaine inhibition. The specific activity of the phoA product, alkaline phosphatase, was elevated in envZ22 mutant strains, while the amounts of both the OmpC and OmpF porins were reduced. Osmotic control of phoA and ompC was retained in the absence of envZ function, but osmoregulation of ompF was lost. Therefore, the envZ product is somehow involved in the complex regulation of all four target genes, but is not solely responsible for osmoregulation.

Bacterial Proteins↗