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Biomedical subjects

D Brown

Publications and source records attributed to D Brown.

At least 883 records · Page 49Linked to original sources

Evidence for a possible regulatory gene (Suc-1) controlling sucrase expression in mouse intestine.

Assays for sucrase carried out on intestinal sonicates prepared from 18 different strains of mice revealed a threefold variation in specific activity, the values for CBA/Ca mice being significantly less than for any other strain. Further comparison of the CBA/Ca versus the C57BL/6J mouse showed this deficiency, which became established 2-4 weeks after birth, to apply to isomaltase as well as sucrase but not to maltase or trehalase. Backcross experiments indicated that this deficiency in sucrase activity was inherited as a single codominantly expressed genetic factor. The ability of the CBA/Ca mouse to regulate sucrase activity in response to changes in diet was also reduced compared to that of the C57BL/6J mouse. No difference could be detected in the affinity of sucrase for its substrate or in the ability of heat to denature sucrase prepared from CBA/Ca and C57BL/6J mice. It is suggested that part of the regulatory region of the gene coding for sucrase-isomaltase is modified in the CBA/Ca mouse and that this locus should be given the notation Suc-1 for future reference.

Animals↗

Nocturnal penile tumescence and serum testosterone levels.

Ten patients with chronic epilepsy were selected; five had high and five had low total serum testosterone levels. Each patient slept for two nights in the sleep laboratory. EEG monitoring and measurements of nocturnal penile tumescence were carried out during sleep. A clear relationship between both total and free serum testosterone levels were found with nocturnal penile tumescence. FSH, LH, SHBG, and prolactin showed no relationship. The five patients with low serum testosterone levels all showed reduced sexual activity.

Adolescent↗

Delayed presentation of traumatic intraperitoneal bladder rupture.

A child with urine ascites as a delayed manifestation of post-traumatic intraperitoneal bladder rupture is presented. The diagnosis was suggested by abdominal CT scan and confirmed with a cystogram. While uncommon, late presentation of intraperitoneal bladder rupture following trauma may occur from masking of a primary laceration or development of secondary rupture at the site of a hematoma in the bladder wall. Since CT may be a primary diagnostic study performed following abdominal trauma, the radiologist should be aware of CT findings suggesting bladder rupture and of the possibility of delayed presentation of this injury.

Child, Preschool↗

Experimental lesions in rats corresponding to advanced human asbestosis.

Rats inhaling chrysotile asbestos developed a progressive interstitial fibrosis similar in most respects to human asbestosis. The earliest lesions were focal deposits of fibrous tissue in the walls of respiratory bronchioles and alveolar ducts. Later alveolar septa between adjacent bronchioles became progressively thickened to produce lesions with similarities to human honeycombing. The thickened septa between alveoli or "micro-honeycomb" spaces were mainly surfaced with cuboidal epithelial cells although some spaces lined by ciliated columnar epithelium were also found. Transmission electron microscopy of these advanced lesions showed that the cuboidal epithelial cells retained most of the characteristics of type 2 pneumocytes but that they frequently exhibited apical cytoplasmic blebs normally associated with the apocrine secretion of Clara cells. Columnar cells exhibited all stages from fully cilitated to cells with only an occasional cilium among the normal cell surface microvilli. Alveolar or micro-honeycomb spaces frequently contained clusters of pulmonary macrophages with their surface processes interdigitated but with no signs of fusion to giant cells. At more than 18 months after the end of dust inhalation these macrophages contained no chrysotile asbestos. The basement membranes beneath the epithelial layers of thickened septa were irregular and often convoluted as well as being much thicker than normal. Microscopic deposits of calcification were frequently found within the basement membrane material. Some thickened septa were relatively acellular, consisting mainly of masses of collagen fibrils but others were cellular and contained many macrophages, fibroblasts, plasma cells and mast cells. In these advanced lesions extremely little chrysotile asbestos was found and this was present in two sites only. Some chrysotile, always as individual fibrils and usually of short length, was present among collagen fibrils in areas of fibrosis and some was present within the thickened basement membranes.

Animals↗

The role of a questionnaire and four biochemical markers to detect cancer risk in a symptomatic population.

The roles of a self-completed symptom questionnaire and four biochemical markers of disease were assessed to determine risk for gastric and colorectal cancer from within a hospital population and a random population. Eight-six patients with cancer, 168 subjects with benign conditions of the stomach and large bowel and 720 individuals from the community at large were investigated. Multivariate analyses of the questionnaire and biochemical data were performed individually and in combination using a data set comprising 54 cancer subjects, 80 patients with benign disease and 200 random individuals. The most favourable predictive equation derived was then applied to the remaining data set to determine its efficacy. In the primary analyses the questionnaire data identified 32 (60%) cancers successfully and using the biochemical markers alone 36 (67%) patients were also correctly classified as cancer bearing. However, the combination of the questionnaire and marker data improved the sensitivity for cancer to 50 cancers detected (92%) (P less than 0.02). Using the predictive equation from this combination of data to identify risk in the second data set 28/32 (88%) cancers were correctly identified with only an 11% false positive rate. An 18 month follow-up for the non-cancer group has to date revealed only one cancer (ca. pancreas). In this limited study, multivariate analysis of questionnaire and biochemical marker data does successfully identify individuals at "high risk' of harbouring gastric or colorectal cancer within a symptomatic population and may have a role in determining priority for investigation for a symptomatic individual.

Aged↗

Seasonal Changes in the Kinetic Parameters of a Photosynthetic Fructose-1,6-Bisphosphatase Isolated from Peltigera rufescens.

The kinetic parameters of the photosynthetic fructose-1,6-bisphosphatase isolated from Peltigera rufescens (Weis) Mudd. were measured on a seasonal basis and during a laboratory-induced temperature acclimation. Both the substrate affinity and Ea changed on a seasonal basis. During the summer, the Ea decreased from 91.8 to 62.3 kilojoules per mole. The K(m) fructose-1,6-bisphosphate measured at temperatures above 25 degrees C was also found to decrease by 50%. This seasonal change in K(m) can be induced by growing the lichen under appropriate conditions for 2 weeks, and is correlated to a change in the net photosynthetic rates. It is hypothesized that this change in fructose-1,6-bisphosphatase is related to the seasonal temperature acclimation process that has been previously reported in this species.

Journal Article↗

Isolation and Characterization of Two Enzymes Capable of Hydrolyzing Fructose-1,6-Bisphosphatase from the Lichen Peltigera rufescens.

Two enzymes capable of hydrolyzing fructose-1,6-bisphosphate (FBP) have been isolated from the foliose lichen Peltigera rufescens (Weis) Mudd. These enzymes can be separated using Sephadex G-100 and DEAE Sephacel chromatography. One enzyme has a pH optimum of 6.5, and a substrate affinity of 228 micromolar FBP. This enzyme does not require MgCl(2) for activity, and is inhibited by AMP. The second enzyme has a pH optimum of 9.0, with no activity below pH 7.5. This enzyme responds sigmoidally to Mg(2+), with half-saturation concentration of 2.0 millimolar MgCl(2), and demonstrates hyperbolic kinetics for FBP (K(m) = 39 micromolar). This enzyme is activated by 20 millimolar dithiothreitol, is inhibited by AMP, but is not affected by fructose-2-6-bisphosphate. It is hypothesized that the latter enzyme is involved in the photosynthetic process, while the former enzyme is a nonspecific acid phosphatase.

Journal Article↗

Purification and characterization of kynurenine formamidase activities from Streptomyces parvulus.

Two forms of kynurenine formamidase (EC 3.5.1.9; aryl-formylamine amidohydrolase) are present in extracts of Streptomyces parvulus. The higher molecular weight enzyme (Mr = 42 000), kynurenine formamidase I, appears to be constitutive and is present at relatively constant but low levels in antibiotic producing and nonproducing cultures, whereas the synthesis of the lower molecular weight form (Mr = 25 000), kynurenine formamidase II, is initiated just prior to the onset of actinomycin formation. It is postulated (i) that kynurenine formamidase II catalyzes the second step in the pathway from tryptophan----actinocin, and (ii) that it is regulated specifically for the specialized function of actinomycin biosynthesis. The role of kynurenine formamidase I is unknown. Formamidase I and II activities were purified from extracts of S. parvulus and kinetic parameters of the two enzymes were determined. Although some of the properties of the two enzymes are quite similar (substrate specificities, Km values), some striking differences were noted (pH and temperature optima, molecular size, chromatographic properties, sensitivity to certain ions and chemicals). Mutant studies suggest that expression of the gene(s) coding for formamidase II activity play an essential role in regulating the formation of actinocin and, hence, antibiotic synthesis. Kynurenine formamidase activity was also found in a representative number of Streptomyces species and related organisms suggesting that the enzyme may function in the degradative metabolism of tryptophan by certain actinomycetes in nature.

Amidohydrolases↗

The "coat" of kidney intercalated cell tubulovesicles does not contain clathrin.

Intercalated cells of kidney collecting ducts contain a population of tubulovesicles in their apical cytoplasm, whose limiting membranes are decorated by arrays of dense, club-shaped projections oriented toward the cytoplasm. These tubulovesicles have been implicated in endo-exocytotic events in these cells. To determine a possible relationship between this "coating" material and clathrin, the coat protein associated with endocytotic coated pits and coated vesicles in other cell types, we applied a monospecific, affinity-purified anti-clathrin antibody to thin sections of rat kidney embedded at low temperature in Lowicryl K4M. We found that no specific labeling was associated with the studlike material of intercalated cell tubulovesicles.

Animals↗

Interactions of lectins with specific cell types in toad urinary bladder. Surface distribution revealed by colloidal gold probes and label fracture.

Colloidal gold probes were used in conjunction with pre-embedding labeling and label-fracture to show the plasma membrane distribution of Helix pomatia lectin (HPL) and wheat germ lectin (WGL) binding sites on different epithelial cell types of toad urinary bladder. Mitochondria-rich cells were virtually unlabeled with HPL, but showed a strong affinity for WGL. Granular cells were weakly labeled with WGL but had a variable affinity for HPL. Strongly labeled granular cells were arranged in either chains or clusters that were surrounded by poorly-stained granular cells. By label-fracture, the distribution of gold-labeled lectins was related to other membrane features seen in freeze-fracture. Neither HPL nor WGL binding sites appeared to be specifically related to the large intramembrane particles that characterize granular cells, or to the rod-shaped intramembrane particles that are a feature of membranes of mitochondria-rich cells. The preferential lectin binding affinity of these functionally distinct cell types provides an important starting point for their isolation and the characterization of their plasma membranes. Furthermore, the label-fracture approach can now be used to examine the plasma membrane modifications that occur in these cells under different physiologic conditions affecting epithelial transport processes.

Animals↗

Changes in the lipid metabolism of the chick embryo with parental age.

A study has been made on the distribution and composition of the lipids associated with the yolk contents, yolk sac membrane, liver, and extrahepatic tissues of chick embryos at Days 15 and 19 of incubation from 25- and 41-week-old broiler-breeder stock. The higher embryo mortality displayed by the eggs from the young breeders was associated with an abnormal distribution of lipid between the tissue pools. The amount of lipid associated with the total yolk, i.e., yolk contents plus yolk sac membrane, of the embryos from the 25-week-old parents at Day 19 of incubation was greater than that of the embryos from the 41-week-old parents, and there was a much higher proportion of lipid still remaining in association with the yolk contents. In the embryos from the young parents, a smaller proportion of embryonic lipid was associated with the extra-hepatic tissues at Day 19 of incubation. Differences were observed in the relative proportions of the major lipid fractions within the yolk and embryonic tissues between the eggs from the two sets of parents. The higher mortality of the embryos from the young parents was associated with a malfunction of yolk lipid assimilation and mobilization from the yolk contents thereby denying access to the major nutrient associated with development during the last week of incubation.

Age Factors↗