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Biomedical subjects

C Sanders

Publications and source records attributed to C Sanders.

At least 19 recordsLinked to original sources
PubMed1997

K-252b potentiation of neurotrophin-3 is trkA specific in cells lacking p75NTR.

K-252b potentiates the neurotrophic effects of neurotrophin-3 (NT-3) in primary cultures of rat central cholinergic and peripheral sensory neurons and in a rat pheochromocytoma PC12 cell line. The ligand and receptor specificity, and role of the low-affinity neurotrophin receptor (p75NTR) in the potentiation response induced by K-252b, are unknown. To address the issues of ligand and receptor specificity of K-252b potentiation, we have examined neurotrophin-induced DNA synthesis ([3H]-thymidine incorporation) in NIH3T3 cells expressing trkA, trkB, or trkC. Neither NT-3 nor K-252b alone could stimulate mitogenic activity in the trkA-overexpressing clone. However, coaddition of K-252b (EC50 of approximately 2 nM) with 10-100 ng/ml NT-3 led to incorporation of [3H]thymidine in trkA expressing cells to a level induced by optimal concentrations of nerve growth factor (NGF). The K-252b- and NT-3-induced [3H]thymidine incorporation correlated with an increase in the tyrosine autophosphorylation of the trkA receptor as well as tyrosine phosphorylation of trk-associated phospholipase C-gamma 1 and SH2-containing proteins. K-252b did not potentiate submaximal doses of NGF, or maximal doses of brain-derived neurotrophic factor (BDNF) or neurotrophin-4/5 (NT-4/ 5) in trkA-expressing cells. Furthermore, K-252b did not potentiate DNA synthesis by submaximal doses of BDNF, NT-4/5, or NT-3 in trkB- or trkC-expressing NIH3T3 cells, suggesting that the potentiation profile for K-252b was specific for NT-3 in trkA-expressing cells. We found no expression of p75NTR in the trk-expressing NIH3T3 cells. This is the first demonstration that K-252b potentiates a trkA-mediated biological nonneuronal response by NT-3 that occurs independent of p75NTR and appears to be both ligand and receptor specific.

3T3 Cells↗
PubMed1996

A gene map of the human genome.

The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.

Amino Acid Sequence↗
PubMed1994

Treatment of septic shock with human monoclonal antibody HA-1A. A randomized, double-blind, placebo-controlled trial. CHESS Trial Study Group.

OBJECTIVE: To compare the effectiveness of 100 mg of HA-1A and placebo in reducing the 14-day all-cause mortality rate in patients with septic shock and gram-negative bacteremia in the Centocor: HA-1A Efficacy in Septic Shock (CHESS) trial, and to assess the safety of 100 mg of HA-1A given to patients with septic shock who did not have gram-negative bacteremia. DESIGN: Large, simple, group-sequential, randomized, double-blind, multicenter, placebo-controlled trial. SETTING: 603 investigators at 513 community and university-affiliated hospitals in the United States. PATIENTS: Within 6 hours before enrollment, the patients had been in shock with a systolic blood pressure of less than 90 mm Hg after adequate fluid challenge or had received vasopressors to maintain blood pressure. These episodes of shock began within 24 hours of enrollment. A presumptive clinical diagnosis of gram-negative infection as the cause of the shock episode and a commitment from the patients' physicians to provide full supportive care were required. MEASUREMENTS: Blood cultures were obtained within 48 hours of enrollment, and death at day 14 after treatment was recorded. Adverse events occurring within 14 days after enrollment were also tabulated. RESULTS: 2199 patients were enrolled; 621 (28.2%) met all enrollment criteria, received HA-1A or placebo, and had confirmed gram-negative bacteremia. Mortality rates in this group were as follows: placebo, 32% (95 and HA-1A, 33% (109 of 328) (P = 0.864, Fisher exact test, two-tailed; 95% CI for the difference, -6.2% to 8.6%). Mortality rates in the patients without gram-negative bacteremia were as follows: placebo, 37% (292 of 793) and HA-1A, 41% (318 of 785) (P = 0.073, Fisher exact test, one-tailed; CI, -0.8% to 8.8%). CONCLUSIONS: In this trial, HA-1A was not effective in reducing the 14-day mortality rate in patients with gram-negative bacteremia and septic shock. These data do not support using septic shock as an indication for HA-1A treatment. If HA-1A is effective in reducing the mortality rate in patients dying from endotoxemia, these patients must be identified using other treatment criteria.

Adult↗
PubMed1994

The Lactational Amenorrhea Method (LAM): a postpartum introductory family planning method with policy and program implications.

It is well accepted that breastfeeding contributes significantly to child survival and child nutrition. Healthful child spacing is associated with improved birth outcomes and maternal recovery. On a population basis, breastfeeding may contribute more to birth spacing than all family planning use combined in many countries. However, while breastfeeding does provide a period of infertility, until recently, there was no reliable way for an individual woman to capitalize on this lactational infertility for her own efficacious child spacing. The Lactational Amenorrhea Method (LAM) is a new introductory family planning method that simultaneously promotes child spacing and breastfeeding, with its optimal nutrition and disease preventive benefits for the infant. LAM, as it is called, is based on the utilization of lactational infertility for protection from pregnancy and indicates the time for the introduction of a complementary family planning method. LAM is recommended for up to six months postpartum for women who are fully or nearly fully breastfeeding and amenorrheic, and relies on the maintenance of appropriate breastfeeding practices to prolong lactational infertility, with the concomitant delay in menses return. A recent clinical trial confirmed the theoretical 98% or higher effectiveness of the method and field trials are demonstrating its acceptability. Nonetheless, some demographers and family planning organizations continue to debate its value. The development, efficacy, and sequelae of the method are presented using data from several studies by the authors.

Amenorrhea↗
PubMed1993

Polypeptide variants of beta-arrestin and arrestin3.

Retinal arrestin (S-antigen) inactivates the phototransduction cascade by binding to light-activated phosphorylated rhodopsin and thereby "arresting" coupling to the G protein transducin. beta-Arrestin (beta arr), a ubiquitous arrestin homolog, acts analogously to desensitize the beta 2-adrenergic receptor by disrupting Gs receptor interaction. In an attempt to identify additional "arrestins" which might regulate the multitude of G protein-coupled receptors, we have isolated two bovine brain cDNAs which encode polypeptide variants of an arrestin homolog which we have designated arrestin3 (arr3). The open reading frames of these two cDNAs are identical except that the long form, arr3L, contains an 11-amino-acid insert between residues 361 and 362. Arr3 is more closely related to bovine beta arr (78% identity) than to bovine visual arrestin (56% identity). Polymerase chain reaction amplification of RNA and immunoblotting of lysates with an arr3-specific antibody suggest that the short form, arr3S, is the major form of arr3 in all bovine tissues and that it is most abundant in the spleen. Furthermore, polymerase chain reaction amplification of beta arr mRNA indicates that in several tissues (lung, liver, spleen, and pituitary), the major form of beta arr lacks 8 amino acids which are present in brain beta arr. Immunoblotting with an antibody which recognizes beta arr and arr3 with equal sensitivity demonstrates that beta arr (either the long or the short polypeptide) is the major arrestin in all (non-photoreceptor bearing) tissues examined. These observations suggest that in some tissues, as many as four arrestin homolog variants may play a role in the regulation of G protein-coupled receptors.

Amino Acid Sequence↗
PubMed1993

AmpG, a signal transducer in chromosomal beta-lactamase induction.

The chromosomal ampC beta-lactamase in Citrobacter freundii and Enterobacter cloacae is inducible by beta-lactam antibiotics. When an inducible ampC gene is introduced on a plasmid into Escherichia coli together with its transcriptional regulator ampR, the plasmid-borne beta-lactamase is still inducible. We have isolated mutants, containing alterations in a novel E. coli gene, ampG, in which a cloned C. freundii ampC gene is unable to respond to beta-lactam inducers. The ampG gene was cloned, sequenced and mapped to minute 9.6 on the E. coli chromosome. The deduced amino acid sequence predicted AmpG to be a 53 kDa, transmembrane protein, which we propose acts as a signal transducer or permease in the beta-lactamase induction system. Immediately upstream of ampG there is another 579-base-pair-long open reading frame (ORF) encoding a putative lipoprotein shown to be non-essential for beta-lactamase induction. We have found that ampG and this ORF form an operon, whose promoter is located in front of the ORF. Located closely upstream of the putative promoter is the morphogene bolA, which is transcribed in the opposite orientation. However, using transcription fusions, we have found that the ampG transcription is not regulated by bolA. In addition, we show that transcription is probably not regulated by either the starvation specific sigma factor RpoS, which controls bolA, or by AmpD the negative regulator for ampC transcription.

Amino Acid Sequence↗
PubMed1992

Intrapulmonary teratoma: a case report and review of the literature.

Intrapulmonary teratomas are rare; only 30 cases have been reported in the world literature. These tumors are thought to originate from the third pharyngeal pouch. They occur equally in men and women and usually are diagnosed in the second to fourth decade of life. They are more often benign than malignant, although malignant lesions may have a favorable postoperative prognosis and benign lesions may exhibit high morbidity and mortality because of their size and location. These tumors present radiographically as lobulated masses that may contain calcification or peripheral collections of air. They most often occur in the upper lobes. The computed tomographic findings of intrapulmonary teratoma are less well known but have been described in two cases. An additional case is presented with a review of the literature and a tabular summary of the characteristics of this unusual entity.

Adult↗
PubMed1992

Transthoracic needle aspiration.

Transthoracic needle aspiration is a safe and highly accurate method in the diagnosis of intrathoracic malignancy and should be considered as the procedure of choice in metastatic disease, mediastinal masses, small peripheral nodules, and chest wall involvement. The ability of the radiologist to treat complications and to perform biopsies on an outpatient basis has led to increased acceptance and use of this procedure.

Biopsy, Needle↗
PubMed1991

Comparison of two mass-selective detectors with special reference to the analysis of residues of anabolics.

In the analysis of residues of anabolic agents the use of combined techniques, especially gas chromatography-mass spectrometry, is of increasing interest. When this method is used for the analysis of residues of anabolics it is very important to have a knowledge of the characteristics of the different types of apparatus on the market and to be sure that the results are not "apparatus-dependent". In this study two mass-selective detectors, the Hewlett-Packard 5970 and the ion trap detector 800, were compared by injecting the same samples of derivatized anabolics (standard solutions) into the two systems.

Anabolic Agents↗
PubMed1991

The radiographic diagnosis of emphysema.

There are many findings of emphysema by conventional radiography, but the most reliable and reproducible is that of overinflation, which is best judged by the height and contour of the hemidiaphragm. Even in expert hands, the diagnosis of emphysema by conventional radiography is 65% to 80% accurate, depending to a large degree on the clinical population studied. Although most patients with severe emphysema are diagnosed correctly, only half of those patients with mild-to-moderate levels of parenchymal destruction are detected. Emphysema is identified by CT as focal, unmarginated, hypodense areas unassociated with fibrosis. Emphysema also may be detected by computer programs selecting pixels with abnormally low attenuation values. By either method, CT is superior to chest radiography in detection of mild and moderate degrees of emphysema and has detection rates of more than 90% and correlation with extent and severity of disease in more than 80% of patients. CT may be more sensitive to the presence of mild emphysema than pulmonary function tests, which are global indications of lung function. HRCT appears to offer a small, but real, advantage over 10-mm collimation in identification of small areas of emphysema, but areas of emphysema smaller than 0.5 cm in diameter are commonly missed, even with HRCT. Wider use of CT for investigation of relatively asymptomatic smokers may allow early diagnosis of emphysema and provide more information of the natural history of this disease, information that is sorely lacking at this time. Assessment of potential therapy such as smoking cessation or antioxidants will only be possible with widespread use of a method that is of relatively low risk, easy to duplicate, and accurate.

Humans↗
PubMed1990

Current role of conventional and digital aortography in the diagnosis of aortic disease.

The availability of the less invasive techniques such as CT, MRI, and digital angiography require reexamination of the indications for conventional screen-film aortography. Because of poor image quality, IV digital subtraction angiography should be limited to congenital aortic disease and follow-up cases. Intraarterial digital angiography can be used as a supplement to or as a replacement for conventional aortography in most cases. Care should be used in substituting intraarterial digital angiography for conventional studies in aortic dissection and aortic rupture; continuing problems with digital subtraction artifacts may introduce error in cases with subtle abnormalities. In aortic aneurysm, CT is usually sufficient for diagnosis and surgical planning with angiography used for inconclusive examinations or more accurate determination of branch involvement. CT is the primary diagnostic examination in suspected chronic or subacute dissection and is the method of choice in sequential studies of patients following medical or surgical therapy for dissection. In acute aortic dissection, either angiography or CT may be used and are equally diagnostic. Angiography is most helpful in aortic dissection with suspected brachiocephalic vessel involvement, coexistant coronary artery disease, or in cases of indeterminate CT. In blunt chest trauma, aortography remains the examination of choice in the diagnosis of aortic transection. CT may play a role in excluding aortic damage in stable patients with a low clinical suspicion of aortic transection.

Acute Disease↗
PubMed1990

Upper respiratory tract infection in children, domestic temperatures, and humidity.

STUDY OBJECTIVE: The aim of the study was to seek for a possible association between the incidence of upper respiratory tract infections and air temperature and humidity in the home. DESIGN: Recordings of temperature and relative humidity were made in living rooms and children's bedrooms over a six month period and related to incidence of upper respiratory tract infection. SETTING: The study was carried out in one general practice of 10,000 patients. PATIENTS: 297 children aged 24-59 months were studied, selected in random order from the practice age-sex register. MEASUREMENTS AND MAIN RESULTS: Temperature and humidity recordings were made with thermohygrograph recorders over six days. Upper respiratory tract infections were recorded (a) retrospectively over the previous 12 months, and (b) during the study period. Past history of acute otitis media and recent family history of respiratory infection were also obtained. No significant association was found between the variables, although the bedrooms of children with reported upper respiratory tract infections were cooler overnight than those of non-infected children (mean difference 0.8 degrees C, 95% confidence limits 0.7 degrees C). No association was found between reported or recorded upper respiratory tract infections and age or type of home, family size, level of occupancy, social class, or smoking habits. Only 15 children (5%) were identified by their parents as having had asthma, but 58 (19.5%) had had a "wheezy chest". A greater proportion of children who wheezed slept in cooler bedrooms, had gas fires rather than central heating, and had more smokers in the house. CONCLUSIONS: No association between upper respiratory tract infection and domestic temperature or humidity levels could be shown in this study. Since dampness is repeatedly presented as a health risk, further study is required.

Child, Preschool↗
PubMed1989

Vitamin K-dependent carboxylase: influence of the "propeptide" region on enzyme activity.

The liver microsomal vitamin K-dependent carboxylase catalyzes the post-translational conversion of specific glutamyl to gamma-carboxyglutamyl (Gla) residues in precursor forms of a limited number of proteins. These proteins contain an amino-terminal extension (propeptide) that is presumed to serve as an enzyme recognition site to assure their normal processing. The free, noncovalently bound propeptide has also been shown to stimulate the in vitro activity of this enzyme. This peptide has now been shown to lower the app Km of a low-molecular-weight Glu site substrate while having no influence on the app Km of the other substrates, vitamin KH2, O2, and CO2/HCO3-. Propeptide addition was shown to have no influence on the ratio of the two products of the enzyme, Gla and vitamin K-2,3-epoxide. Stimulation of carboxylase activity by the propeptide from human factor X was observed in a number of rat tissues and in the liver of a number of different species. Stability of the enzyme in crude microsomal preparations was greatly enhanced by the presence of propeptide. These observations are consistent with the hypothesis that this region of the protein substrates for the carboxylase not only serves an enzyme recognition or docking function but also modulates the activity of the enzyme by altering the affinity for one of its substrates.

Amino Acid Sequence↗
PubMed1989

A comparison of dual-energy digital radiography and screen-film imaging in the detection of subtle interstitial pulmonary disease.

An ROC study is described which compares the performance of three types of images--conventional screen-film, single-energy digital and dual energy bone cancelled (soft tissue) digital--in detecting subtle interstitial pulmonary disease. Marginally detectable nodular and reticulonodular patterns (12 different patterns of each) were superimposed over the lungs of a frozen human chest phantom to simulate the clinical situation. The digital images were formatted on film at full size (ie, 35 cm X 43 cm). A total of 156 images (52 of each type, of which 28 were normal and 24 had simulated pathology) were used in the study and read by five experienced chest radiologists. Using a paired t-test, the areas under the individual ROC curves were compared for three combinations of images--single-energy digital and conventional, soft tissue digital and conventional, and soft tissue and single-energy digital. No statistically significant difference was observed between the conventional and single-energy digital images. The readers performed better with both conventional and single-energy digital images than with the soft tissue digital images at statistically significant levels (P = 0.05 for conventional vs. soft tissue digital and P = 0.02 for single-energy digital vs. soft tissue digital). The results suggest that there is no advantage in employing dual-energy soft tissue images to assist in diagnosing interstitial disease in the clinical setting. They also suggest that spatial resolution requirements are less demanding in digital chest systems that obtain scatter-free images than in digital systems utilizing conventional scatter control techniques.

Evaluation Studies as Topic↗