Biomedical subjects

C L Clark

Publications and source records attributed to C L Clark.

At least 37 records · Page 2Linked to original sources

PubMed1998

Separate DNA elements containing ATF/CREB and IE86 binding sites differentially regulate the human cytomegalovirus UL112-113 promoter at early and late times in the infection.

The human cytomegalovirus (HCMV) UL112-113 promoter represents a useful model for studying temporal regulation of viral gene expression. Stimulation of this promoter by the 86-kDa immediate-early protein (IE86) is controlled by sequences between nucleotides -113 and -59, which include both an ATF/CREB and an IE86 binding site. In transient assays, the ATF/CREB site is essential, and the IE86 site, although nonessential, can enhance transcription. With recombinant viruses, we have assessed the function of these promoter elements in the context of the viral genome. Transcription from the inserted UL112-113 promoter shows the same temporal pattern as the endogenous promoter, including the switch to an upstream RNA start site late in infection. Deletion of sequences containing the IE86 site results in a decrease in the level of early transcription and elimination of late transcription. In contrast, when the ATF/CREB site is deleted, early RNA synthesis is almost completely abolished, but late transcription is comparable to that of the wild type, with repositioning of the RNA start site downstream by the number of nucleotides deleted. Replacement of sequences between -108 and -95 with the HCMV cis-repression signal from the major immediate-early promoter had no effect on the level of late RNAs but resulted in the repositioning of the RNA start site 39 nucleotides upstream. These results suggest that the ATF/CREB site is functional only at early times, while sequences containing the IE86 site modulate the level of early RNAs and may be required for activating late transcription in a distance-dependent manner.

Base Sequence↗

PubMed1998

Trends in alcohol consumption patterns among whites, blacks and Hispanics: 1984 and 1995.

OBJECTIVE: To report national trends in alcohol consumption patterns among whites, blacks and Hispanics between 1984 and 1995, in relation to the recent decline in per capita consumption in the United States. METHOD: Data were obtained from two nationwide probability samples of U.S. households, the first conducted in 1984 and the second in 1995. The 1984 sample consisted of 1,777 whites, 1,947 blacks and 1,453 Hispanics; the 1995 sample consisted of 1,636 whites, 1,582 blacks and 1,585 Hispanics. On both occasions, interviews averaging 1 hour in length were conducted in respondents' homes by trained interviewers. RESULTS: Between 1984 and 1995, the rate of abstention remained stable among whites but increased among blacks and Hispanics. Frequent heavy drinking decreased among white men (from 20% to 12%), but remained stable among black (15% in both surveys) and Hispanic men (17% and 18%). Frequent heavy drinking decreased among white women (from 5% to 2%), but remained stable among black (5% in both surveys) and Hispanic women (2% and 3%). White men and women were two times more likely to be frequent heavy drinkers in 1984 than in 1995. CONCLUSIONS: The reduction in per capita consumption in the U.S. is differentially influencing white, black and Hispanic ethnic groups. The stability of rates of frequent heavy drinking places blacks and Hispanics at a higher risk for problem development than whites. This finding is, therefore, a concern to public health professionals and others interested in the prevention of alcohol-related problems among ethnic groups in the United States.

Adult↗

PubMed1998

Rates of intimate partner violence in the United States.

OBJECTIVES: Estimates of intimate partner violence in the United States based on representative samples have relied on data from one person per household or limited numbers of indicators from both partners. The purpose of this study was to estimate nationwide rates of intimate partner violence with data from both couple members by using a standardized survey instrument, the Conflict Tactics Scale. METHODS: A multistage probability sampling design was used to conduct separate face-to-face interviews in respondents' homes with both members of 1635 representative couples living in the 48 contiguous states. RESULTS: Both partners' reports were used to estimate the following lower- and upper-bound rates: 5.21% and 13.61% for male-to-female partner violence, 6.22% and 18.21% for female-to-male partner violence, and 7.84% to 21.48% for any partner-to-partner violence. CONCLUSIONS: High rates of intimate partner violence in the United States corroborate previous claims that the amount of intimate partner violence is substantial.

Adult↗

PubMed1998

Prevalence, trends, and incidence of alcohol withdrawal symptoms: analysis of general population and clinical samples.

Analyses of the prevalence and incidence of withdrawal symptoms in the general population can provide an estimate of the frequency of alcohol dependence in the population. Similar analyses in people who are being treated for alcoholism or alcohol-related problems can identify the need for and specific types of treatment required for these populations. Three national surveys found that the prevalence of withdrawal symptoms was relatively low in the general population and has remained stable over the past 15 years. The likelihood of experiencing withdrawal symptoms increased with increasing alcohol consumption. No differences in the prevalence of withdrawal symptoms existed among ethnic groups in the general population. In a sample of patients undergoing alcoholism treatment, the prevalence of withdrawal symptoms generally was high, with lower rates among blacks than among whites and Hispanics. The prevalence of withdrawal symptoms in people undergoing treatment after being convicted of driving under the influence fell between that of the general population and that of the treatment sample.

Clinical Trials as Topic↗

PubMed1998

Alcohol consumption among racial/ethnic minorities: theory and research.

Ethnic minorities (e.g., Hispanics, blacks, Asian-Americans, and Native Americans) are still underrepresented in alcohol research in the United States. Furthermore, existing studies often do not take into consideration the variability that exists within each ethnic group, resulting in inaccurate generalizations. Studies among Hispanics have found substantial differences among Hispanic subgroups in drinking patterns and rates of alcohol-related problems. Moreover, no single variable can explain the observed patterns. Similarly, numerous factors have been shown to shape drinking patterns among blacks, including individual and environmental characteristics as well as historical and cultural factors. Different subgroups of Asian-Americans also vary substantially in their rates of drinking and heavy drinking, although their lifetime alcohol use is lower than the national average. Genetic and cultural factors, as well as stress and historic experiences, may influence drinking patterns of Asian-Americans. The widely differing drinking patterns among Native Americans also are likely shaped by a variety of influences.

Alcohol Drinking↗

PubMed1998

Trends in alcohol-related problems among whites, blacks, and Hispanics: 1984-1995.

The objective of this study was to report trends in alcohol problems among whites, blacks, and Hispanics between 1984 and 1995. Data were obtained from two nationwide probability samples of U.S. households, the first conducted in 1984 and the second in 1995. The 1984 sample consisted of 1777 whites, 1947 blacks, and 1453 Hispanics. The 1995 sample included 1636 whites, 1582 blacks, and 1585 Hispanics. On both occasions, interviews (average length, 1 hr) were conducted in respondents' homes by trained interviewers. The results indicate that between 1984 and 1995, alcohol problems were stable among white and black men and increased among Hispanic men. The rates of three or more alcohol problems for men of each ethnic group for 1984 and 1995 were: 12% and 11% for white men, 16% and 13% for black men, and 9% and 16% for Hispanic men, respectively. Problem prevalence was stable and relatively low among women in all three ethnic groups. Overall, the prevalence of alcohol problems continues to be high among men in the United States. Even though recent research has shown that rates of frequent heavy drinking among white men have declined, we found no corresponding decrease in problem prevalence. Rates of frequent heavy drinking and alcohol-related problems between 1984 and 1995 have remained especially high among black and Hispanic men, suggesting that men of these two ethnic groups should be specifically targeted for renewed prevention efforts.

Adolescent↗

PubMed1997

CD, absorption and thermodynamic analysis of repeating dinucleotide DNA, RNA and hybrid duplexes [d/r(AC)]12.[d/r(GT/U)]12 and the influence of phosphorothioate substitution.

Circular dichroism (CD) spectra and melting temperature (Tm) data for five duplexes containing phosphorothioate linkages were compared with data for four unmodified duplexes to assess the effect of phosphorothioate modification on the structure and stability of DNA. DNA and DNA.RNA duplexes. Nine duplexes were formed by mixing oligomers 24 nt long in 0.15 M K+(phosphate buffer), pH 7.0. Unmodified DNA.DNA and RNA.RNA duplexes were used as reference B-form and A-form structures. The CD spectra of the modified hybrids S-d(AC)12.r(GU)12 and r(AC)12.S-d(GT)12 differed from each other but were essentially the same as the spectra of the respective unmodified hybrids. They were more A-form than B-form in character. CD spectra of duplexes S-d(AC)12.d(GT)12 and d(AC)12.S-d(GT)12 were similar to that of d(AC)12.d(GT)12, except for a reduced long wavelength CD band. Sulfur modifications on both strands of the DNA duplex caused a pronounced effect on its CD spectrum. The order of thermal stability was: RNA.RNA > DNA.DNA > DNA.RNA > S-DNA.DNA > S-DNA. RNA > S-DNA.S-DNA. Phosphorothioation of one strand decreased the melting temperature by 7.8+/-0.6 degrees C, regardless of whether the substitution was in a hybrid or DNA duplex. Thermodynamic parameters were obtained from a multistate analysis of the thermal melting profiles. Interestingly, the destabilizing effect of the phosphorothioate substitution appears to arise from a difference in the entropy upon forming the DNA.DNA duplexes, while the destabilizing effect in the DNA.RNA hybrids appears to come from a difference in enthalpy.

Circular Dichroism↗

PubMed1997

Safely withdrawing patients from chronic glucocorticoid therapy.

The withdrawal of patients from chronic glucocorticoid therapy can be a vexing problem. Symptoms of adrenal insufficiency are often subtle, and the potential complications of too-rapid withdrawal are catastrophic. The increased use of inhaled, intranasal and "superpotent" topical preparations will place more and more patients at risk for hypocortisolism. This article presents a safe, practical algorithmic approach to steroid withdrawal that can be determined in the physician's office. The recognition that patients are on maintenance steroid therapy should prompt a constant reevaluation of the need for such therapy, including consideration of an alternate-day drug regimen. The keys to success in withdrawing patients from steroid therapy include improving patient awareness of the signs and symptoms of steroid withdrawal, close follow-up and correct performance of the cosyntropin challenge, which is safe, practical and reliable. During the steroid withdrawal period, it is extremely important that the patient be proactive in identifying subtle symptoms and bringing them to the physician's attention.

Algorithms↗

PubMed1997

Potential availability of patients in a short stay ward for medical student teaching.

The trend towards shorter hospital in-patient stays has decreased the availability of patients for undergraduate medical student teaching. We surveyed 100 consecutive short stay surgical inpatients admitted to hospital on the day of planned operation to determine whether they might be available for student teaching before surgery. We found that there was a median delay of three hours (standard deviation +/-2.3 hours) between the completion of all medical and nursing procedures and the departure of the patient for the operating theatre. All patients were asked if they would agree in principle to participate in student teaching. 98 per cent said they would be willing to be taught upon. We argue that surgical patients attending the short stay ward are a valuable potential source of teaching material.

Education, Medical, Undergraduate↗

PubMed1996

Evidence that orthotopic transposition following rat heterotopic small bowel transplantation corrects overgrowth of potentially pathogenic bacteria.

An overgrowth of pathogenic organisms occurs following rat heterotopic small bowel transplantation. This study assessed whether the bacterial microflora return to normal following subsequent orthotopic transposition of the graft. After 14 days the heterotopic graft was placed into continuity following resection of 15 cm of the host midintestinal loop. Quantitative and qualitative analyses of the intraluminal bacteria were performed studying the resected host intestine, the heterotopic graft at 14 days, and the graft 14 days after transposition. A group of normal rats were used as controls. An overgrowth of Staphylococcus epidermidis evident in the heterotopic graft at 14 days returned to a more normal bacterial profile following orthotopic transposition. These findings suggest that early interposition of a small bowel graft into an orthotopic position may prevent an alteration in the small bowel ecology toward potentially pathogenic organisms capable of translocation.

Abdominal Muscles↗

PubMed1996

Depleted internal store-activated Ca2+ entry can trigger neurotransmitter release in bovine chromaffin cells.

A potential role of the intracellular Ca2+ stores in modulating catecholamine release has been investigated in bovine chromaffin cells maintained in tissue culture. Pharmacological depletion of the stores with a combination of caffeine, histamine and thapsigargin in Ca2+-free media resulted in a significantly greater release of catecholamines on re-exposure to Ca2+-containing media compared with that from non-store depleted cells. The increase in catecholamine release was prevented by intracellular BAPTA indicating that the increase was caused by a rise in Ca2+. Measurement of intracellular free Ca2+ concentration with the fluorescent indicator, fura-2, over the same time-course as the catecholamine release experiments showed that upon restoration of external Ca2+ there was an immediate, substantial and maintained increase in cytosolic Ca2+. It is most probable that the increase in catecholamine release was a consequence of an increase in Ca2+ influx triggered by prior depletion of the internal Ca2+ stores. However, the data suggest that capacitative Ca2+ entry is poorly linked to catecholamine release; although Ca2+ entry on restoration of external Ca2+ was immediate and substantial, the increase in catecholamine release, although quantitatively significant, was slowly realised.

Animals↗

PubMed1996

A difference in the cellular mechanisms of secretion of adrenaline and noradrenaline revealed with lanthanum in bovine chromaffin cells.

A comparison of the effectiveness of the trivalent cation, lanthanum (La3+) relative to Ca2+ in causing adrenaline and noradrenaline release from bovine adrenal medullary chromaffin cells has been made. In cells maintained in tissue culture and permeabilised with digitonin, both La3+ and Ca2+ triggered catecholamine release. La3+ was more effective than Ca2+: the EC50 for La3+ was shifted to the left of that for Ca2+ by close to one order of magnitude for both adrenaline and noradrenaline. With respect to adrenaline, the same maximal release was triggered by the two cations, but with respect to noradrenaline, La3+ triggered a significantly greater release than did Ca2+. Mixtures of experimental media containing both La3+ and Ca2+ caused release of adrenaline and noradrenaline in amounts that approximated closely the sum of the releases caused by Ca2+ and La3+ alone. The data strongly imply that either the release mechanisms for adrenaline and for noradrenaline from their respective chromaffin cells are different, or the cellular mechanisms that regulate release from the two cells are different.

Adrenal Medulla↗

PubMed1996

Identification, analysis, and evolutionary relationships of the putative murine cytomegalovirus homologs of the human cytomegalovirus UL82 (pp71) and UL83 (pp65) matrix phosphoproteins.

We have identified three open reading frames (ORFs) in murine cytomegalovirus (MCMV), designated M82, M83, and M84, which likely encode homologs of the human cytomegalovirus (HCMV) UL82 and UL83 matrix phosphoproteins. These ORFs, in the HindIII C fragment of MCMV, are colinear with the UL82, UL83, and UL84 ORFs of HCMV. M82 encodes a 598-amino-acid (aa) protein with homology to UL82, M83 encodes an 809-aa protein with homology to UL82 and UL83, and M84 encodes a 587-aa protein with homology to UL83 and UL84. Analysis of transcription by Northern (RNA) blotting indicated that the M82 and M83 ORFs are transcribed as 2.2- and 5-kb mRNAs, respectively, at 24 to 48 h postinfection (p.i.), while M84 is transcribed as a 6.9-kb mRNA only at 8 h p.i. All transcripts appear to terminate at the same position 3' of the M82 ORF. Of the products of the three ORFs, only M83 is strongly recognized by hyperimmune mouse serum. The M83 protein is a virion-associated phosphoprotein with an apparent molecular mass of 125 kDa. In MCMV-infected cells, it is detectable by Western blotting (immunoblotting) only at 48 h p.i. in the absence of phosphonoacetic acid, consistent with late gene expression. The M83 ORF is also expressed at high levels in cells infected by a recombinant vaccinia virus and yields a protein which is serologically cross-reactive and comigrates with the authentic MCMV protein in sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

3T3 Cells↗

PubMed1996

Complications of gastroesophageal reflux disease. Esophagitis, acid laryngitis, and beyond.

Gastroesophageal reflux disease is a common disorder that can result in various esophageal and extraesophageal complications. Reflux of gastric contents can cause esophageal mucosal abnormalities, such as ulcers and peptic strictures, as well as pulmonary and otolaryngologic symptoms, including reflux-induced asthma and acid laryngitis. Left untreated, some complications can lead to more severe disorders, such as esophageal adenocarcinoma that develops in patients with Barrett's esophagus. Accurate recognition of these diverse manifestations allows improved identification of patients at risk for reflux-related disorders and aids in proper evaluation and treatment.

Asthma↗

PubMed1996

The immune response in small bowel transplantation.

The immunological problems of small bowel transplantation have not yet been overcome. Frequent severe rejection episodes are common in clinical practice, and GVHD may emerge as a significant complication once rejection is more effectively controlled. Both are caused by the large number of lymphocytes in the graft. There is extensive exchange migration of lymphocytes between graft and host even in the absence of rejection, and persisting donor cells in the host may carry the propensity for GVHD. Various techniques including analysis of host peripheral blood samples are being developed to enable earlier and easier diagnosis of rejection, which should facilitate early treatment and reduce infective complications. The balance between rejection and GVHD can be manipulated experimentally, and clinical trials are under way to determine whether such techniques can improve the outcome for human transplant recipients.

Acute Disease↗

PubMed1995

Content of advertisements for junior doctors: is there sufficient detail?

OBJECTIVE: To determine whether employers follow BMA guidelines on advertisements when advertising for junior doctors. DESIGN: Survey of advertisements for junior doctors in the BMJ's classified advertisements supplement from 12 March to 14 May 1994. SUBJECTS: 300 advertisements for substantive posts for junior doctors. OUTCOME MEASURES: Compliance with BMA guidelines, compared by grade, specialty, and employer (trust or regional health authority); observation of any useful information not included in the guidelines. RESULTS: Only eight advertisements included all the recommended information. Amount of information given was related to grade, specialty, or employer in only one respect: advertisements for basic trainees were more likely than those for higher specialist trainees to include information on pay and hours of work (P < 0.001). CONCLUSION: Advertisements for junior doctors in the BMJ do not comply with BMA guidelines and often contain little useful information for potential applicants.

Advertising↗

PubMed1995

Presence and localization of tumor necrosis factor alpha in the corpus luteum of nonpregnant and pregnant pigs.

The objectives of this study were to determine whether tumor necrosis factor alpha (TNF alpha) is present in porcine corpus luteum (CL) and, if so, to ascertain which cells of the CL were associated with TNF alpha. The influence of the reproductive state of the animals on the amount or cellular localization of TNF alpha in the CL was also investigated. Western blot analysis demonstrated the presence of a 34-kDa immunoreactive TNF alpha-like protein in CL from nonpregnant and pregnant pigs. The intensity of TNF alpha immunostaining in bands observed in Western blots did not differ when luteal protein from nonpregnant pigs or from pregnant pigs was analyzed. Positive immunostaining for TNF alpha, determined by immunocytochemistry, was localized within endothelial cells of luteal sections. Positive immunocytochemical staining was recorded in all reproductive states examined except in CL that had undergone functional luteolysis (reduced progesterone concentration). A single-cell assay for TNF alpha secretion (a reverse hemolytic plaque assay) confirmed in vitro secretion of TNF alpha by a cell type in luteal tissue with a size and nuclear morphology similar to an endothelial cell. The presence of TNF alpha in the endothelial cells in functional CL is consistent with a role for TNF alpha in the regulation of vascular development of the CL in swine.

Animals↗

PubMed1995

Treatment of hypophosphatemia in patients receiving specialized nutrition support using a graduated dosing scheme: results from a prospective clinical trial.

OBJECTIVE: To determine the safety and efficacy of a graduated dosing scheme of phosphorus replacement therapy in patients with hypophosphatemia receiving specialized nutrition support. DESIGN: Prospective clinical trial. SETTING: A 455-bed tertiary care institution, with Level I trauma designation. PATIENTS: Seventy-eight adult patients, followed and co-managed by a multidisciplinary Nutrition Support Service, with a serum phosphorus concentration of < 3 mg/dL (< 0.97 mmol/L) and no evidence of renal insufficiency, calcium or parathyroid disorders, or obesity. INTERVENTIONS: Patients were enrolled into one of three categories based on their serum phosphorus concentration: mild hypophosphatemia (2.3 to 3 mg/dL [0.74 to 0.97 mmol/L]), moderate hypophosphatemia (1.6 to 2.2 mg/dL [0.52 to 0.71 mmol/L]), or severe hypophosphatemia (< 1.5 mg/dL [< 0.48 mmol/L]). Each patient received one intravenous phosphorus bolus dose, based on the assigned category of hypophosphatemia, according to a graduated dosing scheme: 0.16 mM/kg (mild), 0.32 mM/kg (moderate), or 0.64 mM/kg (severe). Serum/blood concentrations of phosphorus, calcium, albumin, magnesium, urea nitrogen, and creatinine were measured for three consecutive days. MEASUREMENTS AND MAIN RESULTS: Sixty-seven patients completed the protocol. There were 31 patients with mild hypophosphatemia, 22 patients with moderate hypophosphatemia, and 14 patients with severe hypophosphatemia. Serum phosphorus concentrations increased significantly (p < .001) in all groups after the phosphorus bolus: 2.6 +/- 0.6 to 3.3 +/- 0.6 mg/dL (0.84 +/- 0.19 to 1.1 +/- 0.19 mmol/L) for the mild group; 1.9 +/- 0.6 to 2.7 +/- 0.6 mg/dL (0.61 +/- 0.19 to 0.87 +/- 0.19 mmol/L) for the moderate group; 1.3 +/- 0.8 to 2.3 +/- 0.8 mg/dL (0.42 +/- 0.26 to 0.74 +/- 0.26 mmol/L) for the severe group. There were no clinically significant changes in serum/blood calcium, albumin, urea nitrogen, or creatinine concentrations and no adverse reactions to the phosphorus regimens throughout the 3-day study period. CONCLUSION: The graduated dosing scheme of phosphorus replacement therapy is both safe and efficacious in patients receiving specialized nutrition support.

Adult↗