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Biomedical subjects

J Whitley

Publications and source records attributed to J Whitley.

At least 19 recordsLinked to original sources
PubMed2005

Dynamic imaging of the lungs using x-ray phase contrast.

High quality real-time imaging of lungs in vivo presents considerable challenges. We demonstrate here that phase contrast x-ray imaging is capable of dynamically imaging the lungs. It retains many of the advantages of simple x-ray imaging, whilst also being able to map weakly absorbing soft tissues based on refractive index differences. Preliminary results reported herein show that this novel imaging technique can identify and locate airway liquid and allows lung aeration in newborn rabbit pups to be dynamically visualized.

Animals↗
PubMed1999

Active immunoneutralization of somatostatin in the sheep: effects on gastrointestinal somatostatin expression, storage and secretion.

In the absence of somatostatin antagonists, somatostatin antisera administered acutely or animals chronically immunized against somatostatin have been used to define the functions of somatostatin. However, the circulating immunoglobulins from immunized animals may contain substantial quantities of endogenous hormones. This has not been examined for somatostatin. We have measured the amount of free somatostatin bound to circulating immunoglobulins in somatostatin-immunized animals and the effect of this sequestering of the free peptide on somatostatin secretion and gastric somatostatin synthesis and storage. The average concentration of somatostatin bound to the antisera was 6.9 nmol/l, about 1000-fold higher than normal circulating levels. Compared to control animals, there was a doubling of somatostatin mRNA in the fundus and a 4-fold increase in fundic somatostatin peptide. Similar increases were seen in pancreas, but the antrum was not significantly affected providing further evidence of distinct regulatory mechanisms between the antrum and fundus. We suggest that withdrawal of active somatostatin activates a regulatory loop to increase fundic somatostatin biosynthesis and storage. The data support the concept that somatostatin autoregulates its own expression at both the RNA and peptide level.

Animals↗
PubMed1998

Adenoviral expression of murine serum amyloid A proteins to study amyloid fibrillogenesis.

Serum amyloid A (SAA) proteins are one of the most inducible acute-phase reactants and are precursors of secondary amyloidosis. In the mouse, SAA1 and SAA2 are induced in approximately equal quantities in response to amyloid induction models. These two isotypes differ in only 9 of 103 amino acid residues; however, only SAA2 is selectively deposited into amyloid fibrils. SAA expression in the CE/J mouse species is an exception in that gene duplication did not occur and the CE/J variant is a hybrid molecule sharing features of SAA1 and SAA2. However, even though it is more closely related to SAA2 it is not deposited as amyloid fibrils. We have developed an adenoviral vector system to overexpress SAA proteins in cell culture to determine the ability of these proteins to form amyloid fibrils, and to study the structural features in relation to amyloid formation. Both the SAA2 and CE/J SAA proteins were synthesized in large quantities and purified to homogeneity. Electron microscopic analysis of the SAA proteins revealed that the SAA2 protein was capable of forming amyloid fibrils, whereas the CE/J SAA was incapable. Radiolabelled SAAs were associated with normal or acute-phase high-density lipoproteins (HDLs); we examined them for their clearance from the circulation. In normal mice, SAA2 had a half-life of 70 min and CE/J SAA had a half-life of 120 min; however, in amyloid mice 50% of the SAA2 cleared in 55 min, compared with 135 min for the CE/J protein. When the SAA proteins were associated with acute-phase HDLs, SAA2 clearance was decreased to 60 min in normal mice compared with 30 min in amyloidogenic mice. Both normal and acute-phase HDLs were capable of depositing SAA2 into preformed amyloid fibrils, whereas the CE/J protein did not become associated with amyloid fibrils. This established approach opens the doors for large-scale SAA production and for the examination of specific amino acids involved in the fibrillogenic capability of the SAA2 molecule in vitro and in vivo.

Acute-Phase Proteins↗
PubMed1996

The pregnant ovine endometrium constitutively expresses and secretes a highly stable bombesin-like peptide, which shares C-terminal sequence but differs structurally from gastrin-releasing peptide.

Previous studies have shown that a peptide closely related to gastrin releasing peptide (GRP) is expressed by the pregnant ovine endometrium throughout gestation, however its molecular form and the mode of its secretion have not been defined. We have partially purified the endometrial GRP-like peptide and characterised it chromatographically. In contrast to other tissues, the main molecular form of endometrial GRP is larger (6-8 kDa versus 1-3 kDa), and based on the increased hydrophobicity of its circulating form after reduction, contains at least one disulfide bond. Reduction and treatment with chaotropic agents showed that the protein is not a cleavage product of pro-GRP bound to a binding protein. Tryptic cleavage demonstrated that the C-terminus of the peptide is closely related to GRP18-27 suggesting that bioactivity is likely. The partially purified peptide remained intact after incubation in ovine plasma for 16 h indicating that it is extremely stable and consistent with an hormonal role during pregnancy. Quantification of peptide from monolayer cultures of ovine endometrial cells showed that the GRP-like peptide was secreted constitutively. These data show that a stable, GRP-like peptide, distinct from the known processing products of pre-pro-GRP is constitutively expressed by the gravid ovine endometrium. Since endometrial GRP has an intact bioactive C-terminus and is mitogenic for numerous tissues including the uterus, then it is likely to play an important regulatory role in ovine pregnancy.

Amino Acid Sequence↗
PubMed1994

A peptide related to gastrin releasing peptide is synthesised and secreted by the ovine endometrium in early pregnancy.

We have previously shown that the peptide immunoreactivity related closely to the mitogen GRP is expressed by the pregnant ovine endometrium during the final third of pregnancy. In this study we have established that GRP is also expressed early in ovine pregnancy and have quantified the temporal changes in synthesis, storage and secretion of GRP in the peri- and post-attachment period. Secreted GRP peptide levels rise 10 fold just prior to implantation, while endometrial peptide and mRNA concentrations increase 4 and 13 fold respectively between day 17 and 20, immediately following attachment and corresponding to the onset of placentome development. The main molecular form of endometrial GRP has similar binding characteristics on RP-HPLC to GRP 18-27, but is larger. We conclude that a GRP-like peptide is expressed by the pregnant ovine endometrium from early in pregnancy until term, and that it is likely to play an important role in fetal or uterine maturation.

Animals↗
PubMed1989

Bedside blood gas and electrolyte monitoring in critically ill patients.

A major advantage of near-patient testing is time savings that facilitate important diagnostic and therapeutic decisions. Recent technologic advances have made available a number of systems that allow for near-patient testing. The reliability of these instruments must be validated in the clinical setting in the hands of their intended users. We evaluated the Gemstat blood gas, electrolyte, and Hct portable analyzer in the critical care setting when used by numerous individuals with no previous laboratory training. Blood gas, Na, K, and Hct results were highly correlated with those from the clinical laboratories (PaO2, r = .96; PaCO2, r = .92, pH, r = .96; Na, r = .93; K, r = .95; Hct, r = .91). The Gemstat represents a new generation of portable, rapid, safe, and accurate instruments that are well suited for ICU settings. The instrument can facilitate clinical management of patients, and may improve patient care.

Blood Gas Analysis↗
PubMed1989

Tumor volume and treatment outcome in small cell lung carcinoma.

The volume of some tumors correlates with local disease control, response, and survival. Small cell lung carcinoma presents with variable and often large intrathoracic masses. We assessed volume by two methods (summation of cross-sectional areas and Simpson's rule for estimating volume) and correlated volume with treatment outcome. Twenty-nine patients with small cell lung carcinoma (12 limited disease and 17 extensive disease) were analyzed for volume outcome correlations. There were five early deaths. Twenty-four had response correlations (11 limited disease and 13 extensive disease). Eighteen of the twenty-four achieved complete response. There was no apparent correlation between complete and/or partial response and pretreatment tumor volume. There was no apparent correlation between survival and volume. The methods of volume assessment correlate well with each other (r = 0.88) and either can be used with accuracy. So far there is also no correlation between chest tumor volume and intrathoracic recurrence. Our projections suggest that there is a low probability of correlating chest tumor volume and either response or survival. This is in keeping with the disseminated nature of the tumor which is its limiting factor in survival.

Carcinoma, Small Cell↗
PubMed1982

Volume determinations in computed tomography.

Modern computed tomographic (CT) scanners allow reasonably high-resolution cross-sectional visualization of most viscera and masses. To determine the accuracy of CT volume estimation, CT volumes of inanimate objects, cadaver kidneys and spleens, and in vivo balloons were performed. Regions of interest were outlined by a hand-operated cursor, and the computer program calculated the cross-sectional area in square millimeters and in pixels. A second computer program used Simpson's rule to calculate the volume from these multiple cross-sectional area. Calculated CT volumes were within +/-10% of directly measured volumes. Tumor masses being treated by chemotherapy were followed up clinically and by CT. Volume changes determined by CT are believed to be equal to and frequently more sensitive than clinical examination. From our experimental CT and clinical experiences, accuracy can be affected by (1) respiratory movement; (2) rapid changes in in vivo blood volume; (3) low CT number-gradient at the objects' periphery; (4) observer error in cursor tracing of the desired structure; and (5) mathematical errors inherent in Simpson's rule. We conclude that CT can estimate volumes of CT definable masses and can be useful in following tumor response to therapy.

Female↗
PubMed1982

Computed tomographic evaluation of carcinoma of the cervix.

To assess the accuracy of computed tomography (CT) in staging advanced carcinoma of the cervix, 18 staging evaluations were performed in 16 patients with locally advanced (FIGO Stage IB-IVA) cervical carcinoma. CT staging results were compared with the results of clinical staging and postoperative staging. CT was accurate in 12/18 (66%) cases, clinical staging was accurate in 10/18 (55%) cases, and clinical staging with cystoscopy was accurate in 14/18 (78%) cases. CT staging failed to detect microscopic pelvic sidewall involvement and bladder involvement when there was no contrast material in the bladder. In the detection of para-aortic lymph node involvement by tumor, there were 12 true-negative, 4 true-positive, 1 false-positive, and 1 false-negative study (sensitivity = 80%, specificity = 92%). It is concluded that CT is equal in accuracy to other clinical staging techniques and offers the advantage of visualizing the tumor, which allows for more accurate determination of radiation portals.

Carcinoma↗
PubMed1982

Liver injury and complications in the postoperative trauma patient: CT evaluation.

Twenty-eight patients with surgically documented and classified hepatic injury were studied by computed tomography (CT) in the postoperative period. CT demonstrated no abnormalities in 12 of these patients, most of whom had sustained simple lacerations of the liver. Of the 16 patients with abnormal scans, perihepatic fluid collections were present in six, five of whom had simple lacerations at surgery. The other 10 patients had CT evidence of parenchymal abnormalities, and all of these had sustained major hepatic injuries. CT is useful in depicting the postoperative anatomy, and in many cases demonstrates the nature and extent of damage; the likelihood of finding an abnormality varies with the severity of the injury, even though repair has been attempted. The frequent problem of postoperative sepsis is also amenable to CT evaluation, but the changes demonstrated are often nonspecific and the possibility of residual hepatic injury has to be considered. Finally, CT can document healing of parenchymal injury.

Abscess↗
PubMed1979

Digital radiology in trauma using small-dose exposure.

The microdose radiology system produces a large-field examination within thirty seconds on a video monitor. This video image can be manipulated in the same manner as a computed tomography (CT) scan. The system was installed at the Maryland Institute for Emergency Services (MIEMS) to examine severely injured patients. No major abnormalities were overlooked during the examination of these patients. The microdose system is useful in providing extensive radiologic information immediately applicable to the care of massively traumatized patients.

Evaluation Studies as Topic↗
PubMedDate not supplied

Effectiveness of small-group self-instruction in radiographic anatomy.

A small-group self-instructional program with 11 slide-tape units was designed to teach medical students radiographic anatomy concurrently with their course in gross anatomy. The effectiveness of the program was examined by administering an objective multiple choice examination at three medical schools. One school offered the slide-tape program alone; one, the slide-tape program plus lecture-demonstrations; and one acted as a control. The results indicate that students will, on their own, learn some radiographic anatomy. With exposure to an objectives-based, small-group slide-tape program, the students can learn significantly more. Such a slide-tape program plus lecture-demonstrations can further enhance learning. Student attitudinal results were uniformly positive toward this slide-tape program.

Anatomy↗
PubMedDate not supplied

Use of the computed tomographic whole body scanner to stage and follow patients with advanced ovarian carcinoma.

Advanced ovarian carcinoma continues to be a difficult tumor to evaluate noninvasively. Recent developments in chemotherapy have enhanced response rates in this disease, thus improving the likelihood of tumor regression. Computed Tomography (CT) allows the noninvasive estimation of tumor extent in patients with ovarian carcinoma. Seventeen patients with epithelial ovarian carcinoma had 22 whole body CT scans performed either just prior to or following laparotomy. For determination of tumor involvement, when the CT was positive, a high pathologic correlation was found at liver, ascitic, peritoneal, mesenteric, and omental sites (sensitivity). When the cT was negative, high pathologic correlation was found at ascitic and mesenteric sites (specificity). Lower and negative correlation at other disease sites is attributed to difficulty of CT detection of small (1 cm) tumor nodules on visceral surfaces. Eighteen patients with advanced ovarian carcinoma were followed prospectively during treatment with repetitive CT scans. CT results were compared with physical examination, other radiologic studies, and clinical status. In 83% (15/18) of patients and 88% (59/67) of CT scans performed, CT was found to contribute useful management information. Clinical decisions were made on the basis of CT alone in 43% (29/67) of scans performed. These data suggest that CT scanning is very useful in the staging and follow-up of patients with ovarian carcinoma and can replace other radiologic procedures, but it is not completely accurate and needs to be correlated with physical examination and in cases without tumors visible with CT, with laparotomy.

Female↗
PubMedDate not supplied

Foetal metabolism, placental transfer and origin of gastrin releasing peptide in the sheep.

1. Plasma gastrin releasing peptide (GRP) is elevated in the foetal and maternal circulations of pregnant sheep. To determine the mechanisms for this increase the synthesis, secretion rate, metabolism and placental transfer of GRP were measured. 2. Foetal metabolic clearance rate of GRP was significantly increased (P < 0.05) compared to the non-pregnant ewe (19.9 +/- 2.6 (s.e.m.) and 11.8 +/- 2.0 mL/min per kg, respectively). Production rate of GRP in the foetus was four-fold higher than in the non-pregnant ewe reflecting the combination of the increased basal concentration and metabolic clearance rate in the foetus. 3. Infused GRP did not cross the placenta. However, endogenous GRP was higher in the umbilical vein than in the umbilical artery, suggesting a uteroplacental origin for some of the GRP in the foetal circulation. 4. Gastrin releasing peptide mRNA was synthesized in the pregnant endometrium with lower amounts found in the pregnant myometrium. No GRP mRNA was detected in the amnion or chorioallantois. 5. The results show that the previously reported increase in foetal concentration of GRP is from foetal and uteroplacental sources and is not a result of immaturity of clearance mechanisms but rather from an increased production of GRP. With the demonstration that the uteroplacental unit synthesizes and stores GRP, additional studies on the regulation of GRP production from these sources were warranted.

Animals↗