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Biomedical subjects

K L Cox

Publications and source records attributed to K L Cox.

At least 19 recordsLinked to original sources
PubMed1992

Graft involvement by Legionella in a liver transplant recipient.

Legionella pneumophila, serogroup 1, was identified by direct immunofluorescence in the lung and liver graft from a 2 1/2-month-old infant who underwent orthotopic liver transplantation because of fulminant hepatic failure secondary to neonatal hepatitis. The patient died of respiratory failure owing to this infection 22 days after transplantation despite treatment with erythromycin lactobionate. To our knowledge, this represents the first reported case of hepatic infection with Legionella in liver transplant recipients.

Fluorescent Antibody Technique↗
PubMed1991

Effects of alcohol intake on plasma fatty acids assessed independently of diet and smoking habits.

1. This study was designed to determine prospectively whether changing alcohol consumption influenced the proportion of plasma linoleic acid independently of diet or smoking habits, and to evaluate changes in the plasma linoleic acid concentration as a potential marker of changes in alcohol consumption. 2. Fasting plasma fatty acid profiles were investigated in 72 male drinkers who were randomly assigned to drink low-alcohol beer or to maintain their usual drinking habits for a period of 4 weeks. 3. At entry to the study, a higher alcohol intake was associated with lower proportions of plasma linoleic acid, arachidonic acid and dihomolinolenic acid and higher proportions of plasma palmitoleic acid, independently of changes in body mass index. Smoking habits were unchanged and there were no major changes in diet during the period of the intervention. 4. Because the plasma palmitoleic acid concentration has been suggested as a possible marker of 'at risk' drinking, we investigated plasma fatty acid concentrations as indicators of alcohol intake. The plasma palmitoleic acid concentration was not a useful discriminator. Indices determined using logistic regression and combining plasma apolipoprotein A-II and linoleic acid concentrations gave better discrimination than either variable alone.

Adult↗
PubMed1991

Liver transplantation in Langerhans' cell histiocytosis (histiocytosis X).

Two children with biopsy-proven LCH underwent successful hepatic transplantation for end-stage liver disease. These patients were thought not to have active LCH disease at the time of transplantation, although one had developed a new osteolytic lesion a few months before the operation and the other had suspicious osteolytic lesions at the time of transplantation. The histologic examination of the excised liver showed features consistent with primary sclerosing cholangitis. The two patients had an excellent recovery with no evidence of progression of LCH or recurrence of the underlying disease in the hepatic allograft at 1 and 3 years after organ transplantation.

Adolescent↗
PubMed1990

Mediastinal pancreatic pseudocysts in children.

Mediastinal pseudocyst is an unusual complication of pancreatitis, with only four cases previously reported in children. The extent of the pseudocyst can be defined by computed tomography or magnetic resonance imaging scan and preoperative aspiration of cyst fluid for amylase level can establish the diagnosis. Endoscopic retrograde cholangiopancreatography to define ductal anatomy can help plan the appropriate drainage procedure. Although exceedingly rare, the diagnosis of pseudocyst should be considered for any cystic mass in the abdomen or thorax, even in the absence of elevated amylase or history suggesting pancreatitis.

Amylases↗
PubMed1990

Controlled comparison of effects of exercise and alcohol on blood pressure and serum high density lipoprotein cholesterol in sedentary males.

1. Seventy-two sedentary male drinkers, aged 20-45 years, and with mean blood pressure (BP) at entry of 132 +/- 1.2/73 +/- 0.9 mmHg, completed a 4 week study during which they were assigned randomly to either drink a low alcohol beer (effectively reducing their weekly alcohol intake from 481 +/- 47 mL to 52 +/- 5 mL) or to continue their normal drinking habits. 2. Within these two groups subjects were further assigned to either a moderate exercise programme of three 30 min sessions per week of stationary cycling at 60-70% maximum workload or to a control light exercise programme where they pedalled against zero or minimal resistance. 3. Both alcohol restriction and moderate exercise were associated with mean falls in bodyweight of 0.5 kg. After adjustment for bodyweight a significant main effect of alcohol restriction on systolic BP (-4.1 +/- 1.7 mmHg, P less than 0.05) and diastolic BP (-1.6 +/- 0.8 mmHg, P = 0.05) was demonstrated. There was no significant main effect of moderate exercise on systolic or diastolic blood pressure despite a significant improvement in physical fitness (maximal oxygen uptake increasing from 33.2 +/- 0.8 mL/kg per min to 35.5 +/- 0.1 mL/kg per min). 4. Significant falls in high density lipoprotein cholesterol (HDLC) and triglyceride levels seen with alcohol restriction were unaffected by the increase in fitness, the magnitude of the fall being similar in both the moderate and light exercise groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Characterization of cholecystokinin receptors on the sphincter of Oddi.

To characterize directly the ability of cholecystokinin (CCK) to interact with receptors on the sphincter of Oddi (SO), we measured binding of 125I-labeled Bolton-Hunter-labeled COOH-terminal octapeptide of cholecystokinin (125I-BH-CCK-8) to tissue sections from the guinea pig SO. Autoradiography localized binding of 125I-BH-CCK-8 over the SO smooth muscle layer. Binding was saturable, specific, dependent on time, pH, and temperature, and was reversible. Binding of 125I-BH-CCK-8 was inhibited by various CCK receptor agonists with the following potencies: CCK-8 much greater than des(SO3)CCK-8 much greater than gastrin-17-I and by various CCK receptor antagonists with the following potencies: L-364,718 greater than proglumide analogue 10 much greater than carbobenzoxy-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-NH2 greater than N2,O2' dibutyryl guanosine 3',5'-cyclic monophosphate. The potencies of agonists in stimulating and of antagonists in inhibiting CCK-8-stimulated SO contractions correlated closely with their abilities to inhibit binding of 125I-BH-CCK-8. Analysis of binding of 125I-BH-CCK-8 to SO tissue sections revealed two classes of CCK binding sites: a high-affinity site [dissociation constant (Kd) 0.2 nM] and a low-affinity site (Kd 70 nM). Atropine or tetrodotoxin (TTX) caused a similar rightward shift of the CCK-8 dose-response curve for stimulation of SO contraction. Comparison of receptor occupation to CCK-8-induced contraction suggested that CCK-8 occupation of the high-affinity binding site correlated with contraction in the absence of atropine and the low-affinity CCK binding with contraction in the presence of atropine or TTX.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Determination of triacylglycerol lipase activity using carbon-13-labeled triacylglycerols and nuclear magnetic resonance spectroscopy: evidence that hepatic lipase hydrolyzes medium-chain triacylglycerols.

Triacylglycerol lipase activity was studied using glycerol [1-13C]trioctanoate mixed with postheparin rat plasma. 13C NMR spectroscopy demonstrated triacylglycerol hydrolysis into free fatty acids with no difference at the 1,3 or 2 glycerol positions. There was no inhibition by high sodium concentration, consistent with lipase of hepatic origin.

Animals↗
PubMed1989

Intravital microscopy: a new in vivo technique for visualizing and quantifying effects of regulatory peptides on choledochoduodenal junction motility.

Using intravital microscopy, we studied the in vivo effects of regulatory peptides on choledochoduodenal junction motility in guinea pigs. During basal and hormone-stimulated periods, intravital microscopy documented rhythmic, asymmetrical, "milking" contractions of the sphincter ductus choledochi (SDC) which occurred independent of sphincter ampullae (SA) contractions or were followed by SA contractions. Cholecystokinin octapeptide (CCK-8) (greater than or equal to 0.01 micrograms/kg) increased the frequency of SDC contractions and at higher doses (greater than or equal to 0.1 microgram/kg) increased the frequency of SA contractions. Pentagastrin (greater than or equal to 1.0 microgram/kg) and secretin (10 micrograms/kg) decreased the contraction frequencies of both sphincters. Biliary manometry demonstrated similar effects of these peptides on the frequency of the SDC and SA contractions, but also showed that CCK-8 (0.1 microgram/kg) increased the amplitude of SDC and SA contractions while pentagastrin (1 microgram/kg) decreased the amplitude of only SDC contractions. Tetrodotoxin and atropine did not affect hormone-induced changes in frequency, but tetrodotoxin reduced the increase in amplitude of contraction caused by CCK-8. We concluded that intravital microscopy provides a sensitive, in vivo technique to visualize and quantify the complex motility of a small structure like the choledochoduodenal junction.

Animals↗
PubMed1989

Bile flow rates and biliary motility quantitated by intravital microscopy.

Intravital microscopy was adapted to document and quantitate in vivo biliary motility and bile flow rates in guinea pigs. The movement of 10 microns diameter fluorescent beads in the bile duct was used to measure bile flow rates. Using this method, bile flow rates were comparable to those determined by measuring the volume of bile collected from the papilla, but greater (P less than 0.01) than the volume of bile collected from a bile duct cannula. During intravital microscopy, biliary contractions were only detected at the choledochoduodenal junction. While fasting, the sphincter ductus choledochi contracted at 6.0 +/- 1.0 per min and the ampulla at 1.2 +/- 0.2 per min. Postprandially, sphincter contractions had a decreased frequency and an increased duration while both duration and frequency of ampullary contractions increased. The volume of bile collected from a bile duct cannula postprandially did not change. This data suggested that the choledochoduodenal junction had a propulsive function and postprandial changes in motility were due to neurohumoral factors rather than passive response to changes in bile flow rates. Intravital microscopy proved to be a sensitive in vivo technique in which to quantitate bile flow rates and biliary motility.

Animals↗
PubMed1988

Identification of serotonin from rabbit upper stomach as a stimulant of in vitro gallbladder contraction.

Using an in vitro rabbit gallbladder bioassay, the distribution and identification of bioactive substances in rabbit gastrointestinal tract were investigated. Comparison of the bioactivities of tissue extracts before and after cholecystokinin was removed by affinity chromatography demonstrated that the distributions of cholecystokinin and non-cholecystokinin substances were different. While cholecystokinin bioactivity per g of tissue was highest in the duodenum, non-cholecystokinin bioactivity was greatest in the upper stomach. The biochemical properties of the non-cholecystokinin substance in the upper stomach could not be distinguished from those of serotonin. These included molecular weights of 176, identical ultraviolet spectra, similar nuclear magnetic resonance spectra, and co-chromatography in HPLC. By weight, serotonin had 1/6th of the bioactivity of cholecystokinin octapeptide. We conclude that the principal gallbladder-contracting substance in rabbit upper stomach is serotonin.

Animals↗
PubMed1988

The noninvasive determination of linoleic acid content of human adipose tissue by natural abundance carbon-13 nuclear magnetic resonance.

A new method to assess noninvasively the proportionate storage of poly- and mono-unsaturated fatty acids in human adipose tissue is described. The method is based on in vivo natural abundance 13C NMR at 1.9 T using a TMR 32/200. Data were acquired with a concentric coil system placed below subcutaneous adipose tissue of the calf or the lower arm. Continuous single-frequency decoupling was used to optimize the signal in the spectral region of interest and minimize potential heating effects. Only adipose triglycerides contributed significantly to the resonance intensities. Typical linewidths for the in vivo 13C resonances were 10-14 Hz resulting in excellent resolution in the region of the unsaturated carbons. Signal-to-noise ratios for the resonance at 128.4 ppm (due to carbon atoms of polyunsaturated fatty acids) were typically 50-90 in 8 min using 0.25s repetition time. The relative storage of polyunsaturated fatty acids was determined by comparing the peak intensity at 128.4 ppm with the intensities of the peaks due to the carbonyl, the glycerol, or the main methyl carbons. High-resolution in vitro NMR of adipose biopsies and various mixtures of triglycerides studied with the in vivo NMR protocols provided further evidence that the described in vivo NMR methods allowed precise information on the relative storage of linoleic acid, the main constituent of the pool of polyunsaturated fatty acids. Conventional gas chromatography was performed on adipose biopsies of two volunteers and resulted in close agreement with the in vivo NMR methods. The average polyunsaturated fatty acid concentration in adipose tissue in seven healthy volunteers was 19.83 mol% +/- 1.74 (SD) as determined by in vivo NMR, consistent with conventional studies based on gas chromatography of biopsied material. Preliminary data on three cystic fibrosis patients showed a decreased polyunsaturated fatty acid concentration of 13.12 mol% +/- 2.73 (SD). The high accuracy of this method and its noninvasive character should be especially valuable in clinical research and diagnosis as repetitive adipose biopsies can be avoided.

Adipose Tissue↗
PubMed1988

Adipose tissue abnormalities in cystic fibrosis: noninvasive determination of mono- and polyunsaturated fatty acids by carbon-13 topical magnetic resonance spectroscopy.

Natural abundance in vivo carbon-13 topical magnetic resonance (TMR) spectroscopy was used to assess human adipose tissue stores of essential (polyunsaturated) fatty acids. TMR spectra were obtained from 17 normal volunteers and nine cystic fibrosis patients using an Oxford TMR-32 with a surface coil that sampled tissue less than 1 cm below the surface of an extremity. Spectra were taken of lower leg adipose tissue. Polyunsaturated fatty acid content was determined by comparing peak heights of the polyunsaturated peak (internal unsaturated carbons, 128 ppm) to C-1 carboxyl groups (173 ppm). Monounsaturated fatty acid content was determined by subtracting the polyunsaturated peak from the peak observed for all unsaturated carbons (external unsaturated carbon, 130 ppm) and dividing this ratio by the carboxyl peak. In vivo TMR of normal volunteers resulted in observed polyunsaturated fatty acid content of 17.8 +/- 2.1% and a monounsaturated content of 44.8 +/- 3.8%. The polyunsaturated and monounsaturated fatty acid content of adipose tissue from the cystic fibrosis patients was 15.0 +/- 2.0% (p less than 0.005 versus normal volunteers) and 47.8 +/- 6.5% (NS), respectively. One cystic fibrosis patient without fat malabsorption had decreased adipose polyunsaturates, whereas another patient on high calorie gastrostomy feeds had normal levels. Carbon-13 TMR spectroscopy is a sensitive, noninvasive technique for determining essential fatty acid status in subcutaneous adipose tissue of patients with cystic fibrosis.

Adipose Tissue↗
PubMed1987

Highly transformable mutants of Streptomyces fradiae defective in several restriction systems.

Streptomyces fradiae JS85 is a mutant defective in tylosin production and an efficient recipient for conjugal transfer of tylosin genes. JS85 was mutagenized with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and derivatives defective in restriction were isolated by sequential selection for increased transformability by several plasmid DNAs. From the number of mutation and selection cycles required to eliminate most restriction, it was estimated that wild type S. fradiae expressed at least five restriction systems. From the patterns of restriction enzyme digestion of chromosomal DNA observed in the series of mutants that became progressively less restricting, it was suggested that wild type S. fradiae normally expresses modification (and presumably restriction) systems similar or analogous to PstI, XhoI, ScaI and EcoRI. The least restricting mutant of S. fradiae was readily transformable by many plasmids, including a bifunctional cosmid vector containing a large insert of Streptomyces DNA.

Bacteriophages↗
PubMed1987

Effects of growth and maturation on biliary structures of guinea pigs.

The biliary system and major duodenal papilla of male guinea pigs were examined in vivo using intravital microscopy. Study of the photomicrographs and videotape recordings indicated that biliary organs changed with age and growth of the guinea pigs. Physiological data including the frequency of sphincteric contractions were recorded and efforts were made to correlate these data with changes in structure thought to be due to maturation. The volume of smooth muscle in the bile duct sphincter (measured using histological sections) increased with age as did surface area of the mucosa. The bile duct was separate from the pancreatic duct in each of 28 guinea pigs. Study of the guinea pig extrahepatic biliary system (EBS) allowed the isolated examination of effects of maturation on bile duct capacity. The anatomical reason for this is that the ampulla of the bile duct emptied into the duodenum (independently of the pancreatic duct) at the major duodenal papilla. The duct of the pancreas entered the duodenum distally (caudally) to the major duodenal papilla on the minor duodenal papilla. The separation of biliary and pancreatic ducts simplified the making of casts of the EBS. It is important to consider this feature in selection of a model for studies of bile duct function in living animals. Three anatomical techniques were selected to focus from differing perspectives on growth-related changes that occurred among the EBS of neonatal, juvenile and adult animals. These techniques were: The capacity (volume) of bile contained within the EBS was determined using plastic casts of the system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Biliary motility: postnatal changes in guinea pigs.

Intravital microscopy, a new in vivo technique, documented age-dependent changes in choledochoduodenal junction motility in male guinea pigs. In the guinea pig, the choledochoduodenal junction served as a pump that actively emptied its luminal contents into the duodenum. In the neonates (less than or equal to 1 wk old), this choledochoduodenal junction pump was not fully developed. Unlike the older guinea pigs, some neonates had an incompetent sphincter ductus choledochi (SDC) allowing retrograde flow of bile during ampullary contractions. While fasting, neonates had decreased frequency of SDC (1.2 +/- 0.4 contractions/min) and ampullary (0.1 +/- 0.1 contractions/min) contractions as compared to juveniles (4-6 wk old) (SDC = 6.4 +/- 1.0; ampulla = 1.2 +/- 0.2 contractions/min) and adults (greater than 1 yr old) (SDC = 6.7 +/- 1.6; 0.8 +/- 0.2 contractions/min). Following a meal (Ensure), unlike older guinea pigs, the neonate did not have a significant increased duration and decreased frequency of SDC contractions. Altered neonatal SDC motility correlated with an incompletely developed SDC including decreased muscle mass and mucosal thickness. By 4 wk of age, choledochoduodenal junction motility was similar to that of the adult. These developmental alterations in junctional motility and structure may affect the flow of bile into the duodenum contributing to physiologic cholestasis and decreased intraduodenal bile acids seen in neonates.

Animals↗
PubMed1987

Orthotopic liver transplantation in patients with cystic fibrosis.

An 11-year-old boy who had cystic fibrosis underwent an orthotopic liver transplantation. His immediate postoperative course was not unusually complicated when compared with other liver transplant recipients. Transplantation did not correct abnormalities in the sweat test or the respiratory disease. Cholestasis due to obstruction of the recipient duct with tenacious bile was cleared by instilling N-acetylcysteine into the duct. On the 48th day after the transplantation, he died of an intraventricular and intracerebral hemorrhage caused by an Aspergillus brain abscess. We conclude that certain patients with cystic fibrosis may be appropriate candidates for liver transplantation, but their pre- and post-operative management may need to differ from other liver transplant recipients.

Aspergillosis↗
PubMed1986

Cloning and expression of a tylosin resistance gene from a tylosin-producing strain of Streptomyces fradiae.

A gene conferring high-level resistance to tylosin in Streptomyces lividans and Streptomyces griseofuscus was cloned from a tylosin-producing strain of Streptomyces fradiae. The tylosin-resistance (Tylr) gene (tlrA) was isolated on five overlapping DNA fragments which contained a common 2.6 Kb KpnI fragment. The KpnI fragment contained all of the information required for the expression of the Tylr phenotype in S. lividans and S. griseofuscus. Southern hybridization indicated that the sequence conferring tylosin resistance was present on the same 5 kb SalI fragment in genomic DNA from S. fradiae and several tylosin-sensitive (Tyls) mutants. The cloned tlrA gene failed to restore tylosin resistance in two Tyls mutants derived by protoplast formation and regeneration, and it restored partial resistance in a Tyls mutant obtained by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) mutagenesis. The tlrA gene conferred resistance to tylosin, carbomycin, niddamycin, vernamycin-B and, to some degree, lincomycin in S. griseofuscus, but it had no effect on sensitivity to streptomycin or spectinomycin, suggesting that the cloned gene is an MLS (macrolide, lincosamide, streptogramin-B)-resistance gene. Twenty-eight kb of S. fradiae DNA surrounding the tlrA gene was isolated from a genomic library in bacteriophage lambda Charon 4. Introduction of these DNA sequence into S. fradiae mutants blocked at different steps in tylosin biosynthesis failed to restore tylosin production, suggesting that the cloned Tylr gene is not closely linked to tylosin biosynthetic genes.

Cloning, Molecular↗