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Biomedical subjects

J Hall

Publications and source records attributed to J Hall.

At least 343 records · Page 19Linked to original sources

Biodistribution and magnetic resonance imaging of cross-linked DTPA polysaccharides.

Large polysaccharide complexes, cross-linked with DTPA and chelated with gadolinium have been tested for various potential uses for magnetic resonance imaging (MRI) in rats. Biodistribution and pharmacokinetic data for several of the soluble polymers are presented and compared with Gd-DTPA and GdCl3. By varying the initial polysaccharide length and ratio of DTPA to glucose units, polymers of molecular weights (mol wt) from 17,000 to several million were formed, giving soluble material, gels, or particles. The larger polymers (mol wt greater than 100,000) demonstrate prolonged enhancement of the intravascular space, striking renal enhancement, and moderate hepatic uptake. Small particulate material (less than 10 microns) was also successfully used for intravascular enhancement. The material is metabolized and excreted in urine.

Animals↗

The N-terminal region of an endoglucanase from Pseudomonas fluorescens subspecies cellulosa constitutes a cellulose-binding domain that is distinct from the catalytic centre.

The substrate specificity of an endoglucanase (EGB) from Pseudomonas fluorescens subspecies cellulosa was determined. The enzyme was most active against barley beta-glucan, but showed significant activity against amorphous and crystalline cellulose. EGB was purified to homogeneity by affinity chromatography with crystalline cellulose (Avicel). The Mr of the purified enzyme was 50,000, which is in good agreement with the size of EGB deduced from the nucleotide sequence of the celB gene, coding for EGB. The N-terminal region of the mature form of EGB showed strong homology to another endoglucanase and to a xylanase expressed by the same organism; homologous sequences included highly conserved serine-rich regions. Truncated forms of celB, in which the gene sequence encoding the conserved domain had been deleted, directed the synthesis of a functional endoglucanase that did not bind to crystalline cellulose. This indicates that the conserved region of endoglucanases and xylanases expressed by P. fluorescens subsp. cellulosa constitutes a cellulose-binding domain, which is distinct from the active centre. The possible role of this substrate-binding region is discussed.

Amino Acid Sequence↗

Influence of branched chain amino acid infusions on wound healing.

Branched chain amino acids (BCAA) may serve as a major oxidative fuel for skeletal muscle during periods of starvation. This study compared the ability of protein-undernourished rats to heal musculo-aponeurotic wounds of the abdominal wall when they were infused with solutions containing 45% BCAA or 8% BCAA (conventional TPN). Although the provision of 45% BCAA tended to result in better nourished animals and significantly increased plasma glutamine concentrations, this was not associated with improved healing.

Amino Acids, Branched-Chain↗

Psychosocial and physical activity changes after gastric restrictive procedures for morbid obesity.

Gastric restrictive procedures for morbid obesity are frequently performed to reduce problems arising from the physical limitations and social isolation of massive obesity. Numerous reports have described changes in weight after gastric restrictive operations, yet few studies have documented changes in the secondary effects of obesity. This report deals with changes in psychosocial status and physical activity occurring in 240 patients who remained in the study 3 years after surgery. These patients were members of a group of 310 patients who were entered into a prospective randomized trial to assess the relative benefits of three forms of gastric restrictive procedure. Prior to operation, and at yearly intervals after operation, the physical activities and psychosocial status of each patient was assessed by a standardized semi-structured interview. At the time of the three-year interview the median weight loss for these patients was 29.5 kg which represents 53% of excess weight lost. This weight loss was associated with a marked reduction in the amount of food eaten. There was a significant increase in the number of patients smoking more than 20 cigarettes a day and a mild increase in alcohol intake. There were significant improvements in the level of self-image and state of happiness. The social lives and sex lives of the majority of patients were improved and a significantly greater number of patients reported being in a stable emotional relationship at 3 years after operation than did so pre-operatively. There was a marked increase in the number of patients in full-time or part-time employment from 38% prior to surgery to 60% at 3 years after operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Removal of apoprotein-B-containing lipoproteins by plasmapheresis using immobilized phosphorylcholine-binding protein affinity adsorbent.

Rat serum phosphorylcholine binding protein was earlier shown to bind lipoproteins containing apoproteins B and E from human very low and low density lipoproteins. The present studies were undertaken to show the effectiveness of rat serum phosphorylcholine-binding protein immobilized on Sepharose affinity column to remove apoprotein-B-containing lipoproteins from normal and hypercholesterolemic rabbit plasma, when used in a plasmapheresis system. The maximum in vitro binding of very low and low density lipoproteins from hypercholesterolemic rabbit plasma to the affinity adsorbent was Ca2+ dependent, and the cholesterol bound to the column at the optimum calcium concentration (2.5 mM) was 21% of the total plasma cholesterol applied. The in vivo binding of total cholesterol from normal and hypercholesterolemic rabbit plasma during plasmapheresis ranged from 0.22 to 7.7%. Total mass of cholesterol bound ranged from 3.86 and 27.52 mg at plasma cholesterol concentrations 13.8 and 282 mg/dL, respectively. Most (greater than 95%) of the bound cholesterol was associated with very low and low density lipoproteins. These studies show the ability of immobilized rat serum phosphorylcholine-binding protein to lower the atherogenic apoprotein-B-containing lipoproteins from plasma of hypercholesterolemic rabbits.

Adsorption↗

Clinical review 15: Management of ovulatory disorders with pulsatile gonadotropin-releasing hormone.

Pulsatile GnRH therapy has yet to achieve widespread acceptance as an alternative to exogenous gonadotropin therapy in women with hypothalamic amenorrhea and complete GnRH deficiency. However, when a physiologically based replacement regimen of pulsatile GnRH is used, a high rate of ovulation and conception can be anticipated in patients with complete GnRH deficiency and hypothalamic amenorrhea. Women with polycystic ovarian syndrome may also benefit from pulsatile GnRH, although rates of ovulation are lower. Pretreatment with a GnRH agonist may improve these rates considerably, but experience is limited. Whether an iv or sc route of administration is chosen, a simplified clinical monitoring protocol can be created which requires a minimum of patient monitoring while assuring maximum safety. Seventy five nanograms per kg appears to be a reasonable initiating dose, with subsequent increases in those who do not respond. The frequency of GnRH administration is best based on the GnRH pulse frequency in normal women. However, further information is needed to determine whether such a variable frequency is clearly superior to a fixed frequency regimen. When used appropriately, pulsatile GnRH is safe, effective, and offers an excellent alternative to conventional gonadotropin therapy for women with disordered endogenous GnRH secretion. Most importantly, and as opposed to exogenous gonadotropin therapy, pulsatile GnRH can be administered by most physicians in the office setting without the necessity of on-line E2 monitoring. This feature will enable more patients to receive treatment by their local physicians, whereas exogenous gonadotropin therapy should be administered by appropriately equipped referral centers. In the future, further studies will be required to determine which other categories of patients might benefit from pulsatile GnRH.

Adult↗

Improved survival in ARDS patients associated with a reduction in pulmonary capillary wedge pressure.

The survival and ICU length of stay of 40 ARDS patients admitted to the ICU were analyzed to determine if a management strategy of lowering the pulmonary capillary wedge pressure (Ppw) was associated with an increased survival or a decreased ICU length of stay. ARDS was defined as three or four quadrant alveolar filling roentgenographically, a PaO2 less than 80 mm Hg with an FIO2 greater than .5 and a Ppw less than 18 mm Hg. Patients were divided into two groups: group 1 included all patients in whom there was a reduction of Ppw by at least 25 percent, and group 2 included patients in whom there was no, or less than a 25 percent reduction in Ppw. Survival was statistically different between the groups with 12 of 16 group 1 patients and seven of 24 group 2 patients surviving to hospital discharge. This difference remained statistically significant after stratifying patients by age and the APACHE II severity of illness index. We conclude that this retrospective analysis supports the notion that treatment of low pressure pulmonary edema with reduction of Ppw is associated with an increased survival.

Adult↗

Intra-abdominal pressure and renal function after surgery to the abdominal aorta.

It has been suggested that an elevated intra-abdominal pressure (IAP) can impair renal function. In a prospective longitudinal study, the IAP of 42 patients admitted to an intensive care unit after abdominal aortic surgery was monitored. When compared with the other patients, the 22 patients (53%) who developed renal impairment had higher IAP (17.8 +/- 6.0 mmHg versus 14.1 +/- 4.8 mmHg; P less than 0.01) and APACHE II scores (15.6 +/- 6.0 versus 9.8 +/- 4.6; P less than 0.01). Each of the 10 patients who were re-explored because of haemodynamic instability and oliguria had an IAP of greater than 18 mmHg (positive predictive value = 85%, negative predictive value = 62%). Following re-exploration, the urinary output increased by 115 +/- 40 mL/h (P less than 0.01), and the IAP decreased by 10 +/- 3 mmHg (P less than 0.01). Although it is concluded that an IAP greater than 18 mmHg is a significant risk factor for the development of impaired renal function, it was not possible to prove a causal relationship between these events. Nevertheless, such a relationship has been demonstrated in animal and human models.

Abdomen↗

Accuracy of prediction of the liveweight of horses from body measurements.

Fifty-three horses, all but two of them over two years of age and varying in type, sex and liveweight (230 to 707 kg) were weighed and seven different body measurements were recorded in duplicate by a single operator. The best overall prediction of liveweight using an equation with two variables was found to be: liveweight (kg) = (umbilical girth [cm])1.78 X (length of body from tuber ischii to elbow [cm]0.97/3011). This equation had an adjusted R2 value of 94.9 per cent and was derived from the pooled data, because differences of sex, type and weight did not significantly affect the relationship. The stable behaviour of the relationship was demonstrated by the fact that about 95 per cent of the residuals lay within +/- 53 kg, giving an average error of 4.7 per cent. The accuracy of prediction of the equation was better than the accuracy of four other established equations. A nomogram based on the equation is given.

Animals↗

Further studies on the mechanism of inhibition of intestinal chylomicron transport by Pluronic L-81.

This study explored further the hypothesis that intestinal cells have two pathways for producing large triacylglycerol-rich lipoprotein particles. The hydrophobic surfactant Pluronic L-81 (L-81) inhibits formation of chylomicrons (containing triacylglycerol synthesized from dietary fatty acids and monoacylglycerol, through the monoacylglycerol pathway), but not formation of very-low-density lipoproteins. L-81 does not inhibit lymphatic lipid transport during infusion of egg phosphatidylcholine, whose fatty acid is processed through the alpha-glycerol phosphate pathway and is transported in lymph in very-low-density lipoproteins. Thus, the first part of this study tested whether L-81 cannot inhibit the alpha-glycerol phosphate pathway, and thus L-81 can only affect chylomicron lipid secretion. Intestinal lymph fistula rats were infused with a lipid emulsion containing [1-14C]oleic acid, but no monoacylglycerol, to ensure that the oleic acid will be channeled to the alpha-glycerol phosphate pathway. Experimental rats received 1 mg/h of L-81 in their emulsion whereas control rats lacked L-81. Lymphatic triacylglycerol output, measured both chemically and radioactively, was markedly suppressed in the experimental rats as compared to the controls. Thus, these data indicate that the reason why lipid transport was unaffected by L-81 when egg phosphatidylcholine was infused was not because of the pathway used for the resynthesis of triacylglycerol from phosphatidylcholine. In the second part of this study, we measured the appearance time for chylomicron (in control rats) and for very-low-density lipoprotein (in L-81-treated rats). The appearance time is defined as the time between placement of radioactive fatty acid into the intestinal lumen and the appearance of radioactive lipid in the central lacteal. The average appearance time for the control rats was 10.8 min, which was significantly shorter than the 16.2 min in the L-81-treated experimental rats. This difference in appearance time further supports the hypothesis that chylomicron and very-low-density lipoprotein are packaged separately in the enterocytes and only the formation of chylomicron is inhibited by L-81.

Animals↗

Hyaluronic acid-stimulating activity in sera from the bovine fetus and from breast cancer patients.

The sine qua non of malignancy is the ability of tumor cells to migrate and invade surrounding tissue. There are many substances that have been described that enhance cell motility and hyaluronic acid is prominent among these. Hyaluronic acid is a high molecular weight alternating disaccharide polymer found in abundance in extracellular matrices whenever rapid cell proliferation or tissue regeneration and repair occur. It creates a permissive environment for cell motility during embryogenesis, and high levels of hyaluronic acid also correlate with increased tumor cell invasion and aggressiveness. Little is known about the regulation of hyaluronic acid production, either in normal tissue or in malignancy. In this study, we characterize a hyaluronic acid-stimulating activity in fetal calf serum and describe a similar activity in the sera of breast cancer patients. The stimulating activity was measured by placing aliquots of test substance on fibrosarcoma cells. These indicator cells, which synthesize copious quantities of hyaluronic acid, respond to stimulation in a time- and dose-dependent fashion. The fetal calf serum hyaluronic acid-stimulating activity is maximum early in gestation and then falls rapidly to essentially no activity at term. This activity was partially purified from 120-day fetal calf serum by concanavalin A-Sepharose affinity and ion exchange chromatography and is accounted for by a glycoprotein with a molecular weight of 150,000 on gel filtration under native conditions. The sera of breast cancer patients with measurable burden of disease also contained hyaluronic acid-stimulating activity, which was not present in normal serum donors or in breast cancer patients without evidence of disease. The production of this stimulating activity may contribute to the development of the malignant phenotype by inducing hyaluronic acid-rich microenvironments that are permissive to tumor cell invasion and metastases.

Animals↗

Role of specific lysine residues in the reaction of Rhodobacter sphaeroides cytochrome c2 with the cytochrome bc1 complex.

The reaction of Rhodobacter sphaeroides cytochrome c2 with the Rb. sphaeroides cytochrome bc1 complex was studied by using singly labeled cytochrome c2 derivatives. Cytochrome c2 was treated with chlorodinitrobenzoic acid to modify lysine amino groups to negatively charged carboxydinitrophenyllysines and separated into eight different fractions by ion-exchange chromatography on a Whatman SE 53 (sulfoxyethyl)cellulose column. Peptide mapping studies indicated that six of these fractions were modified at single lysine amino groups. Each of the derivatives had the same Vmax value as native cytochrome c2 in the steady-state reaction with the Rb. sphaeroides cytochrome bc1 complex. However, the Km values of the cytochrome c2 derivatives modified at lysines 10, 55, 95, 97, 99, and 106 were found to be larger than that of native cytochrome c2 by factors of 6, 2, 3, 32, 13, and 8, respectively. These results indicate that lysines located in the sequence 97-106 on the left side of the heme crevice have the greatest involvement in binding the cytochrome bc1 complex. The involvement of lysine 97 is especially significant because it is located in an extra loop comprising residues 89-98 that is not present in eukaryotic cytochrome c.

Amino Acid Sequence↗

Effects of chlorinated benzenes on diatom fatty acid composition and quantitative morphology. I. 1,2,4-Trichlorobenzene.

Cells of the diatom Cyclotella meneghiniana were exposed in a closed system to 0.245 ppm 1,2,4-trichlorobenzene. Response to this chlorinated benzene was monitored over a period of 5 days by quantitative ultrastructure and fatty acid percent composition. Over the time period examined, 41 significant morphological changes and 12 significant changes in fatty acid composition were observed. Autophagic-like vacuoles were frequently observed, indicating lysis of cellular constituents. In general, there was an increase in the C20:5 fatty acid, which may be indicative of photosynthetic impairment, since this fatty acid probably substitutes for linolenic acid in diatoms. The most significant numbers of changes were observed after 8 hr of exposure to this lipophilic toxicant, and these changes occurred in membranous organelles. It is suggested that the daily photoperiodic variation in lipid content of phytoplankton may be an important consideration in evaluating effects of lipophilic toxicants.

Chlorobenzenes↗