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Biomedical subjects

T Hall

Publications and source records attributed to T Hall.

At least 73 records · Page 4Linked to original sources

Enhancing magnetic resonance images using water bags.

Fascial planes between tissues are separated by connective tissue, fat, and blood vessels. Magnetic resonance imaging displays surface anatomy and soft tissues. Our team has been successful in demonstrating brachial plexus nerves as a model of magnetic resonance anatomy. Radiologists have devised methods to increase the resolution of images by suppressing noise and increasing the sharpness of the image. We added water bags to a 0.3 tesla permanent magnet suppressing the noise and increasing the signal to image our patients. The images proved to be sharper.

Humans↗

Circumsporozoite protein heterogeneity in the human malaria parasite Plasmodium vivax.

Phenotypic heterogeneity in the repetitive portion of a human malaria circumsporozoite (CS) protein, a major target of candidate vaccines, has been found. Over 14% of clinical cases of uncomplicated Plasmodium vivax malaria at two sites in western Thailand produced sporozoites immunologically distinct from previously characterized examples of the species. Monoclonal antibodies to the CS protein of other P. vivax isolates and to other species of human and simian malarias did not bind to these nonreactive sporozoites, nor did antibodies from monkeys immunized with a candidate vaccine made from the repeat portion of a New World CS protein. The section of the CS protein gene between the conserved regions I and II of a nonreactive isolate contained a nonapeptide repeat, Ala-Asn-Gly-Ala-Gly-Asn-Gln-Pro-Gly, identical at only three amino acid positions with published nonapeptide sequences. This heterogeneity implies that a P. vivax vaccine based on the CS protein repeat of one isolate will not be universally protective.

Amino Acid Sequence↗

Expression site associated genes of Trypanosoma brucei rhodesiense.

Upstream of at least some telomere-linked genes for the variant surface glycoproteins (VSGs) of African trypanosomes are expression site associated genes (ESAGs) whose transcription is co-ordinated with the transcription of the adjacent VSG gene [Cully et al. (1985) Cell 42, 173-182]. The function of the corresponding ESAG proteins is not known. Here we show the sequences of two members of the ESAG-I family that are upstream of the VSG genes expressed in metacyclic variant antigen types 4 and 7 of Trypanosoma brucei rhodesiense. The corresponding metacyclic ESAG-I proteins of about 330 amino acids display extensive positional identity both with each other and with two other ESAG-I proteins of Trypanosoma brucei brucei. Only about 7% of the positions are occupied by a different amino acid in each of the four putative ESAG proteins while 40% of the positions are identical. Thus, the ESAG-I proteins are much more highly conserved than are the VSGs studied to date.

Amino Acid Sequence↗

Specificities of antibodies that inhibit merozoite dispersal from malaria-infected erythrocytes.

When malaria schizont-infected erythrocytes are cultured with immune serum, antibodies prevent dispersal of merozoites, resulting in the formation of immune clusters of merozoites (ICM) and inhibition of parasite growth. Antigens recognized by these antibodies were identified by probing two dimensional immunoblots of Plasmodium falciparum antigens with antibodies dissociated from immune complexes present at the surface of merozoites in ICM. Total immune serum recognized 88 of the 135 protein spots detected by colloidal gold staining, but antibodies dissociated from immune complexes recognized only 15 protein spots attributable to no more than eight distinct antigens. Antigens recognized by antibodies that inhibit merozoite dispersal include the precursor to the major merozoite surface antigens (gp195), a 126-kDa serine-repeat antigen (SERA), the 130-kDa protein that appears to bind to glycophorin (GBP130), and the approx. 45-kDa merozoite surface antigen. One other antigen (230/215-kDa doublet) was identified by using antibodies affinity purified from recombinant expression proteins. The identities of the other three antigens (150 kDa, 127 kDa and less than 30 kDa) were not determined. This approach provides a strategy for identifying epitopes accessible at the merozoite surface which may be important components of a multivalent vaccine against blood stages of P. falciparum.

Amino Acid Sequence↗

Chlorpromazine, administered in vivo and in vitro, inhibits the efflux of bile acids in freshly isolated rat hepatocytes.

Although it has been speculated that chlorpromazine may alter the transhepatic movement of bile acids from plasma to bile, the effect of chlorpromazine on various determinants of bile acid transport in isolated rat hepatocytes remains incompletely defined. In particular, there is little information about the effect of chlorpromazine on the release of bile acids from freshly isolated hepatocytes. Therefore, we examined the effect of chlorpromazine, administered in vivo and in vitro, on the efflux rate of radiolabeled bile acids in freshly isolated rat hepatocytes. In an isolated haptocyte system, it is not possible to distinguish the sinusoidal plasma membrane function of efflux (back diffusion) from the canalicular plasma membrane function of excretion. Therefore, efflux, as used in this manuscript, reflects both back diffusion and excretion. In vitro, chlorpromazine produced a rapid dose dependent significant (P less than 0.05) decrease of the bile acid efflux rate in freshly isolated hepatocytes. This decrease in bile acid efflux was observed at chlorpromazine concentrations which did not alter hepatocyte plasma membrane permeability (viability), as measured by intracellular potassium content, release of lactate dehydrogenase, and trypan blue exclusion. Moreover, in freshly isolated hepatocytes from chlorpromazine pretreated rats, a significant (P less than 0.05) decrease in the bile acid efflux rate was also observed, and this decrease in efflux was similar in magnitude to the decrease in bile acid efflux observed following exposure of freshly isolated hepatocytes to chlorpromazine in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cranial arteriovenous malformations in neonates: color Doppler imaging with angiographic correlation.

Five neonates with cranial arteriovenous malformations were studied with color Doppler sonography. Excellent correlation was found between sonography and subsequent angiography. In three patients with vein of Galen aneurysms, sonography showed a cystic structure with rapid or swirling flow. Careful adjustment of the color Doppler system was required to demonstrate flow in another patient with a dural arteriovenous malformation. An arteriovenous fistula in a fifth patient appeared as an area of increased flow. Arterial feeders and major draining veins were visualized in all five patients. Color Doppler imaging also was used to assess the effect of embolic or operative therapy in three of the patients. We conclude that color Doppler sonography is able reliably to characterize flow patterns in neonatal cranial arteriovenous malformations. Color Doppler imaging also is helpful in assessing flow after embolic or surgical therapy.

Cerebral Angiography↗

Primary structure of a Plasmodium falciparum malaria antigen located at the merozoite surface and within the parasitophorous vacuole.

DNA encoding an antigen of 101,000 apparent molecular weight from the human malaria parasite Plasmodium falciparum was cloned and sequenced. Genomic DNA from the Camp strain covering the complete coding region along with cDNA from the FCR3 strain covering 81% of the coding region were obtained. The cloned DNA specified a full-length protein of 743 amino acids which included two tandemly repeated regions, one near the amino terminus containing eight hexapeptide repeats of sequence TVNDEDED, and the second near the carboxyl terminus containing primarily KE and KEE repeats. The latter repeated region is encoded by a 174-base stretch of mRNA containing only a single pyrimidine. Except for a putative leader sequence located at the amino terminus of the protein, the protein is hydrophilic and highly charged with a calculated isoelectric point of 5.6. Sequences from the Camp and FCR3 strains are very close and are also nearly identical to the partial cDNA sequence of the acidic basic repeated antigen (ABRA) protein from the FC27 strain (Stahl, H.D., Bianco, A.E., Crewther, R.F., Anders, R.F., Kyne, A.P., Coppel, R. L., Mitchell, G.F., Kemp, D.J., and Brown, G.V. (1986) Mol. Biol. Med. 3, 351-368). ABRA was previously shown to be located at the merozoite surface and in the parasitophorous vacuole. Because of its location and because it becomes complexed to merozoites when schizonts rupture in the presence of immune serum, ABRA is a candidate component of a malaria vaccine.

Amino Acid Sequence↗

Oxmetidine (H2 receptor antagonist) induced cytotoxicity in isolated rat hepatocytes.

Oxmetidine, a new and more potent analogue of the H2 receptor antagonist, cimetidine, was recently withdrawn from clinical trials because of associated hepatotoxicity. We investigated the potential hepatotoxicity of the drug in vitro and in vivo in the rat. In addition, we investigated, in in vitro experiments, the potential hepatoxicity of other gastric acid inhibitory drugs (cimetidine, ranitidine, omeprazole and nolinium bromide). In in vitro experiments, oxmetidine, at various concentrations, was added to isolated hepatocyte incubations and cytotoxicity was assayed by trypan blue exclusion. In in vivo experiments, oxmetidine was administered both i.p. and orally, and hepatotoxicity was assessed by serum biochemical measures (transaminases, alkaline phosphatase, 5' nucleotidase, gamma glutamyl transpeptidase) and liver histopathology. In the in vitro studies, the addition of oxmetidine to the hepatocyte incubations was associated with significant (P less than 0.001) dose and time dependent cytotoxicity. However, the in vivo experiments revealed no significant changes in serum biochemistry and no significant alterations in liver histopathology up to 72 h following the administration three different dosages of oxmetidine. Of the other gastric acid inhibitory drugs, only nolinium bromide was associated with significant (P less than 0.001) in vitro cytotoxicity. Our in vitro observations establish that oxmetidine is cytotoxic to isolated rat hepatocytes and suggest that nolinium bromide be further evaluated for potential hepatotoxicity.

Aniline Compounds↗

Radionuclide evaluation of liver transplants.

Orthotopic liver transplantation is now an established technique for treating patients with various forms of end stage liver disease. The number of centers performing the procedure is increasing and, as the number of transplant recipients in the population increases, many institutions performing nuclear medicine studies will be confronted with requests to evaluate these patients. While a variety of radionuclides are proving useful in this evaluation, the 99mTc iminodiacetic acid (IDA) compounds, particularly 99mTc diisopropyl IDA (DISIDA), will probably account for the majority of radionuclide evaluations of these patients because they are well suited to monitor both structural and functional changes of the graft. The primary application of radionuclide studies is focused in the postoperative period, when problems with the vascular and biliary anastomoses, rejection, infections, and bile leaks all produce alterations in radionuclide hepatobiliary studies. Abnormalities such as rejection and infection produce primarily functional, rather than structural changes and are not easily differentiated based upon the kinetics of 99mTc-DISIDA extraction and excretion by the liver, serial imaging and correlation with clinical data is necessary in such situations. Quantitative analyses of kinetic 99mTc IDA (DISIDA) studies and quantitative approaches with other compounds such as 99mTc galactosyl-neoglycoalbumin (NGA) may permit better assessments of relatively subtle changes in liver function in the posttransplant period.

Bile Duct Diseases↗

Effects of adsorbed water vapor on the adsorption rate constant and the kinetic adsorption capacity of the Wheeler kinetic model.

A recent trend in occupational safety and health has focused on the use of respiratory protective equipment to supplant engineering controls as the primary means of protecting workers from toxic substances. Respirator adsorbent cartridges have been demonstrated to have a finite capacity to adsorb toxic vapors. The knowledge of when this limit is approached or has been exceeded is crucial to the user. The Wheeler kinetic breakthrough model has been shown to describe accurately organic vapor penetration through beds of activated carbon. The model, however, does not account for competitive adsorption of water vapor or other organic vapors. The investigations reported here demonstrate the effect of adsorbed water vapor on the kinetic adsorption parameters (kinetic rate constant and kinetic saturation capacity) of the Wheeler equation. Adsorbent beds were equilibrated at varying concentrations of water vapor and then challenged with carbon tetrachloride vapor-laden air. Dry carbon had an initial rate constant of 62.5 s-1 and a kinetic adsorption capacity of 0.36 g of adsorbed CCl4/gram (g/g) of adsorbent. These parameters decreased in proportion to the amount of water vapor adsorbed, with the minimum predicted values occurring at 100% relative humidity. The minimum experimental value for the kinetic rate constant was 17.6 s-1, a decrease of 73% from the dry carbon values. The minimum predicted value for the kinetic adsorption capacity was 0.16 g/g, a decrease of 45%.

Adsorption↗

Primary liver tumors in children: comparison of CT and MR imaging.

A prospective study was performed at two institutions to determine the role of magnetic resonance (MR) imaging in the evaluation of primary pediatric liver tumors. The study compared the usefulness of MR imaging and computed tomography (CT) in providing a correct diagnosis, assessing resectability, and determining tumor recurrence in 23 children with liver tumors. The information obtained with both modalities was correlated with surgical data. The results indicate that the accuracy of MR imaging in helping to differentiate benign from malignant lesions is high and identical to that of CT, but not good enough to obviate surgical diagnosis. While all five hepatocellular carcinomas were correctly diagnosed preoperatively with both modalities, neither CT nor MR imaging could help differentiate these carcinomas from aggressive hepatoblastoma or primary hepatic lymphoma. MR imaging helped correctly predict tumor resectability in all 18 children with malignant hepatic tumors; in one, exact tumor extension was misjudged with CT. Postoperative MR studies suggested tumor recurrence in three children who had unremarkable CT examinations. Second-look surgery showed recurrent tumor in two and fibrosis with chronic inflammation at the surgical margin in the third child.

Adolescent↗

Expression of estramustine-binding protein (EMBP) and the proliferation-associated antigen Ki-67 in prostatic carcinomas.

The expression of EMBP and the proliferation-associated antigen Ki-67 was studied in in vitro cultured prostatic carcinoma cells and in tumor tissues removed by transurethral electroresection (TUR). EMBP was found to be expressed predominantly in the moderately differentiated carcinomas. A technique based on the immunohistochemical analysis of fine needle specimens was also evaluated. This technique is of potential interest in prospective studies and in monitoring the effect of therapy. Ki-67 was found to be expressed in the prostatic carcinoma cell line (DU-145) studied, as well as in TUR specimens. This antigen reflects the proliferative characteristics of the tumor and may prove useful with respect to prognostic information and choice of appropriate therapy.

Antibodies, Monoclonal↗

Elevation of serum aluminum in humans on a two-day sucralfate regimen.

Serum aluminum concentrations were determined in ten healthy subjects treated with phenytoin 500 mg and with sucralfate and phenytoin in a crossover fashion. Each subject received four 1,000-mg sucralfate tablets between 8 AM and 10 PM one day before the study, and this was repeated during the study day. A total of eight doses of sucralfate was administered over the two-day period. Serum samples were drawn at 0, 2, 4, 8, 12, 24, 32, and 48 hours after administration. The areas under the serum aluminum concentration-time curves before and after sucralfate (mean +/- SD) were 496.0 +/- 80.9 and 770.9 +/- 146.6 hr-ng/mL, respectively. This increase is statistically significant (P less than .01), indicating that serum aluminum levels are elevated even after two days of treatment with sucralfate. The results from this study are not in agreement with the only other report on this subject.

Adult↗

CT-findings in ARDS.

The CT features of 28 patients with ARDS are described. Diffuse lung consolidation, multifocal patchy involvement and lobar or segmental disease were observed. Large lung cysts as well as small cysts producing a "swiss-cheese" appearance of the parenchyma, were detected. These findings were not regularly appreciated on chest radiographs. The overall mortality of our 28 patients was 72.7% (22 out of 28). Patients with lung cysts showed a trend toward higher mortality (87.5% or 13 out of 16). Other unexpected findings were basilar lung abscesses and an empyema. In 15 out of 28 patients, CT scans provided additional information, not obvious on bedside chest radiographs and led to a change in management in five patients.

Adult↗

Surgical management of peritoneal dialysis catheters in children: five-year experience with 1,800 patient-month follow-up.

Currently at our institution more than 90% of the children with end-stage renal disease are managed with continuous ambulatory peritoneal dialysis (CAPD) in preference to hemodialysis until a successful transplant is accomplished. Recent refinements in CAPD catheters and dialysis techniques have greatly added to the many medical, psychological, and economic advantages of CAPD compared with chronic hemodialysis. Ninety-three patients less than 21 years of age underwent insertion of 167 peritoneal dialysis (PD) catheters over a 5-year period. A variety of PD catheters were used, including 121 (73%) double-cuff Tenckhoff catheters, 22 (13%) single-cuff, and 24 (14%) column disc catheters (Lifecaths, Physio-Control Corp, Redmond, WA). There were three (3%) noncatheter-related mortalities and minimal significant morbidity during the 1,819 patient-months of catheter use. Exit site infections (61%) and peritonitis (59%) were frequent but minor complications, occasionally requiring catheter replacement. Other noninfectious complications included abdominal hernias (42%), dialysis leaks (14%), distal cuff extrusion (11%), catheter obstruction (7%), and hydrothorax (2%). Forty-five of the 60 hernias (75%) were surgically repaired in patients while receiving CAPD. Persistent or recurrent peritonitis was common with Pseudomonas, Serratia, and fungal infections and often resulted in catheter removal and loss of the peritoneal dialysis membrane. Catheter survival for the double-cuff Tenckhoff was significantly better (P .005) than the single-cuff or Lifecath. Based on this experience we have found that using specific operative techniques for CAPD catheter placement and early surgical management for severe peritonitis reduces the incidence of complications and modality failure.

Adolescent↗

Determination of organic vapor respirator cartridge variability in terms of degree of activation of the carbon and cartridge packing density.

The protection provided by carbon-containing organic vapor respirator cartridges depends in part on the packing density of the carbon in the cartridges and its degree of activation. Large variations in these parameters could have significant effects on the service-life of respirator cartridges. Variability among commercially available organic vapor respirator cartridges was examined with regard to the following characteristics: the particle size distribution, amount of carbon and packing density of the carbon in the cartridges and the degree of activation of the carbon. The degree of activation was determined by measuring the maximum adsorption space and the structural constant of the carbon. These two parameters--Wo (cm3/g) and k (cal/M)-2--are constants in the Dubinin/Radushkevich (D/R) model from which physical absorption onto microporous adsorbents, such as activated carbon, are described. Respirator cartridges from three different suppliers were examined. Significant variability (11-40%) in the amount and the degree of activation of the carbon occurred between cartridges of different manufacturers, as well as among cartridges of an individual manufacturer.

Carbon↗