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Biomedical subjects

S Young

Publications and source records attributed to S Young.

At least 253 records · Page 14Linked to original sources

Glottic closure and high flows are not essential for productive cough.

For about 150 years, there has been emphasis on the importance of glottic closure and high flows in coughing. During voluntary coughing in normal subjects, the main expiratory flow usually begins as thoracic and abdominal pressures are rising. However, sometimes it starts at peak pressure whereas at other times flow and pressure rise together. Plateau flow in single coughs remains relatively constant in the face of large changes in pressure. In a group of coughs following a single inspiration, the fall in pressure is less during plateau flow. Consequently, for the same oral flows, it is likely that the mean linear velocity in the intrathoracic airways will be greater than in a single cough. Recordings have also been made of early morning involuntary coughing in patients with obstructive airways disease. Flow, volume and sound were recorded and sputum expectoration was noted. Sputum expectoration usually occurs after groups of coughs following single inspirations. Hence the movement of the equal pressure point peripherally may be important. These patients have very low flows and yet their coughs are productive. Sound often occurs during the whole of the low flow period immediately before the main expulsive phase. This could only occur if the glottis was open. Thus productive cough can occur without glottic closure and with low airflows.

Asthma↗

The complete primary structure of protein kinase C--the major phorbol ester receptor.

Protein kinase C, the major phorbol ester receptor, was purified from bovine brain and through the use of oligonucleotide probes based on partial amino acid sequence, complementary DNA clones were derived from bovine brain complementary DNA libraries. Thus, the complete amino acid sequence of bovine protein kinase C was determined, revealing a domain structure. At the amino terminal is a cysteine-rich domain with an internal duplication; a putative calcium-binding domain follows, and there is at the carboxyl terminal a domain that shows substantial homology, but not identity, to sequences of other protein kinase.

Amino Acid Sequence↗

v-ras genes from Harvey and BALB murine sarcoma viruses can act as initiators of two-stage mouse skin carcinogenesis.

Activated Harvey murine sarcoma virus ras genes were introduced into epidermal cells in vivo by direct application of retroviruses to mouse skin. Subsequent treatment with the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced benign papillomas, some of which progressed to invasive carcinomas. Initiation with virus was irreversible for at least 4 months, since TPA treatment after this latency period produced papillomas within 4 weeks. Analysis of viral integration sites showed that carcinomas are clonal in origin. Both papillomas and carcinomas express virus-specific ras mRNA and the viral form of ras P21 protein. The results show that activated ras genes can replace chemical carcinogens in initiation of mouse skin carcinogenesis. This system presents a novel approach to in vivo analysis of the biological role of oncogenes in epithelial tumorigenesis.

Animals↗

The effect of desferrioxamine on transferrin receptors, the cell cycle and growth rates of human leukaemic cells.

The effect of the iron chelator, desferrioxamine, on transferrin binding, growth rates and the cell cycle was investigated in the human leukaemic cell line, K562. At all concentrations of the chelator (2-50 microM) binding of 125I-transferrin was increased by 24 h and reached a maximum at 72-96 h. Maximum binding (6-8-fold increased) occurred in cells treated with 20 microM-desferrioxamine, in contrast with control cells which, at 96 h, showed a 50% decrease over initial binding. Scatchard analysis at 4 degrees C showed that this increased binding was due to an increase in the number of receptors, as the Kd was similar in induced (1.8 nM) and control (1.5 nM) cells. After 96 h cells, cultured with 20 and 50 microM-desferrioxamine accumulated 59Fe from bovine transferrin at over twice the rate found with control cells, reflecting the increase in transferrin receptors. Although iron uptake was unimpaired by the chelator there was a dose-dependent inhibition of cell growth, with control cells completing three divisions in 96 h and those in 10 microM-desferrioxamine only two divisions. At the highest concentration (50 microM), cell division was abrogated although cell viability was maintained (85%). In contrast, DNA synthesis was not markedly affected, except at 50 microM-desferrioxamine when incorporation of [3H]thymidine was 52% of that in control cells. Flow cytometry revealed that there was a progressive accumulation of the cells in the active phases of their cycle (S, G2 + M). Desferrioxamine may increase transferrin receptors in two ways: by chelating a regulatory pool of iron within the cell, and by arresting cells in S phase when receptors are maximally expressed.

Cell Cycle↗

Home parenteral nutrition in a child with Menetrier disease.

A 4-year-old boy is described with abdominal pain, emesis, weight loss, hypoproteinemia and edema. The diagnosis of Menetrier disease was made based on radiographic studies, gastroscopy and gastric biopsy. There was little response to medical treatment and enteral feedings were poorly tolerated for many weeks. Although Menetrier disease in children has a benign and transient course, we found the use of home hyperalimentation significantly shortened the length of hospitalization and provided adequate nutritional support until the gastric lesions began to resolve.

Child, Preschool↗

A comparison of the oxidative reactions of neutrophils from a variety of species when stimulated by opsonized zymosan and F-met-leu-phe.

Bovine, ovine and porcine blood neutrophils produced less superoxide and consumed less oxygen than human neutrophils when they were challenged with serum-treated zymosan. These differences were not related to methodological considerations or the origin of the serum used to treat the zymosan. When the two main methods of neutrophil isolation were applied to human neutrophils, no differences in the particle stimulated respiratory bursts were observed. The bacterial chemotactic peptide, F-met-leu-phe, which enhances superoxide production of human neutrophils whether or not they are challenged with serum-treated zymosan, did not increase superoxide production of neutrophils from cattle, sheep or pigs under either of these conditions. We conclude that, if our understanding of these host defence mechanisms in domesticated animals is to match that of man, further detailed studies of animal neutrophils are necessary.

Adult↗

Partial splenectomy with the CO2 laser: an alternative technique.

Because total splenectomy has been shown to affect immunocompetence in children, partial splenectomy is advocated as an alternative to total splenectomy in traumatic injury as well as in treatment of benign cysts. Present techniques include elaborate hemostatic techniques and extensive suture repair which has led to the development of massive abdominal adhesions. We have investigated CO2 laser sealing of splenic wounds to obviate the need for extensive repair and to minimize intraabdominal reaction. Five dogs underwent partial splenectomy with a scalpel. Hemostasis was obtained with CO2 laser coagulation; a defocused laser beam at 8 W (power density 30-50 W/cm2). After 3 weeks, the laser sealed splenic tissue was amputated and, on this occasion, hemostasis was obtained using a standard suture technique of Teflon pledget-bolstered chromic sutures. Three weeks later the dogs were explored and the sutured splenic tissue was removed. Gross findings on the first exploration demonstrated no signs of hemorrhage and minimal adhesions of the laser sealed spleens. In contrast, exploration after suture repair revealed dense adhesions containing the spleen, omentum, mesentery, and small and large bowel. Microscopic examination of the laser sealed spleen showed a zone of injury only 2-3-mm thick. Excellent hemostasis of the cut surface of the spleen can be accomplished using the CO2 laser. In addition, the minimal depth of injury and the absence of foreign material in the peritoneal cavity make this an attractive alternative to conventional methods.

Animals↗

The external limiting membrane in developing normal and dysplastic canine retina.

Development of the external limiting membrane of the retina in English springer spaniel fetuses and neonates with incipient stages of retinal dysplasia and in normal mongrel fetuses and neonates was examined using transmission electron microscopy and the freeze-fracture technique. The external limiting membrane of the retina of normal canine fetuses was composed of zonulae adherentes in which there were focal areas of apparent apposition between adjacent ventricular cell membranes. Freeze-fracture examination revealed gap junctions within the external limiting membrane that were composed of 8-10 nm P-face particles in aggregates of variable size and shape. These junctions corresponded to areas of focal membrane apposition. Tight junction strands were also identified in deep E-face grooves which were located perpendicular to the external limiting membrane. At day 46 of gestation in incipiently dysplastic English springer spaniel fetal eyes, there was a marked decrease in the size and area occupied by gap junctions within the external limiting membrane as compared with retinas of mongrel control fetuses at the same age and of other age groups. This apparent loss of gap junctions, coincident with the incipient onset of histologically detectable dysplastic events in the sensory retina, may contribute to the morphogenesis of the defect.

Animals↗

Intracellular forms of iron during transferrin iron uptake by mitogen-stimulated human lymphocytes.

Transferrin receptors expressed by mitogen stimulated human lymphocytes mediate the uptake of transferrin iron into haem, ferritin and a non-haem, non-ferritin component. In spite of different rates of iron uptake by cells from different individuals, the proportional incorporation of 59Fe into these components was similar, suggesting that there was an obligatory relationship between the different forms of iron in the cells. By 3 h over 60% of the iron taken up was incorporated into ferritin while less than 10% was found in haem. Initially (10 min) non-haem, non-ferritin iron comprised 70% of total iron and this diminished to 30% by 3 h. At 10 min 80% of iron in the non-haem, non-ferritin component was retained by anti-transferrin affinity columns indicating it was transferrin-bound. The proportion retained fell to reach a steady state level of 50% by 60 min. These results indicate that 10-20% of the iron in the cells was not recognized as transferrin, ferritin or haem iron. The finding that iron incorporation into this unidentified pool reached equilibrium while that into haem and ferritin increased suggests the iron may act as a precursor for functional and storage compounds.

Chromatography, Affinity↗

Possible new method to improve detection of diabetic retinopathy: Polaroid non-mydriatic retinal photography.

Two retinal cameras (Canon CR2 45NM and CR3 45NM) have recently become available and are capable of producing an instant colour photography of a 45 degree field of retina, including the macula and optic disc, without dilatation of the pupils being necessary. The ability of each camera to detect diabetic retinopathy was compared with that of doctors in diabetic clinics using ophthalmoscopy during busy clinic hours. The CR3 was found to be considerably superior to the CR2 in terms of quality of photograph because it can use a smaller pupil. Overall, the detection rate of the camera was more than four times higher than that of ophthalmoscopy through undilated pupils and more than twice as high as that of ophthalmoscopy through dilated pupils. Lesions missed by ophthalmoscopy but detected by the camera included soft exudates and circinate rings of hard exudates, sometimes encroaching on the macula. Though various aspects of this system of screening for diabetic retinopathy, in particular its ability to detect new retinal vessels, have not yet been assessed, the system may prove beneficial in the detection and monitoring of diabetic retinopathy.

Diabetic Retinopathy↗

Congenital tracheal stenosis in lambs induced by maternal ingestion of Veratrum californicum.

Seven of nine lambs born to six ewes gavaged with Veratum californicum root and rhizome material on days 31, 32 and 33 of gestation died from asphyxia within 5 minutes after birth. Five of the seven were autopsied and found to have severe stenosis of the trachea. None of the 12 lambs born to seven control ewes had tracheal stenosis. The defect was characterized by lateral flattening of the trachea throughout its entire length. Cartilaginous tracheal rings were reduced in number, nonuniform in size and shape, irregularly spaced, and with abnormal orientation. The rings were thinner than those of control tracheas, and had zones of chondrogenesis on outer and inner surfaces which were of equal width, rather than of unequal width as in controls. The smaller size and relatively noncurved shape of the cartilaginous rings of the stenotic trachea resulted in a nondistended lumen.

Animals↗

Amyloid plaques in spongiform encephalopathy of mule deer.

Amyloid plaques were demonstrable in central nervous system tissues of adult captive mule deer affected with chronic wasting disease, a transmissible primary spongiform encephalopathy. Plaques were detected in tissues of 13 of 21 (62 per cent) spontaneously affected animals from 2 to 4 years of age or older, but were not found in 16 unaffected deer of from a few months to 12 years of age.

Age Factors↗

Cilia in the fetal and neonatal canine retina.

Cilia in the canine retina were examined at 40, 46 and 50 days of gestation and at birth by scanning electron microscopy, transmission electron microscopy, and by the freeze-fracture technique. Cilia were similar in all age groups examined. Scanning electron micrographs showed them to be smooth-surfaced conical to tubular extensions arising from putative photoreceptor inner segments. Cilia when freeze-fractured contained variable numbers of circumferential rows of 10 nm P-face particles: these constitute the ciliary necklace. Transmission electron micrographs showed the ciliary membrane to contain electron-dense beads which corresponded to the ciliary necklace seen in freeze-fracture replicas. The ciliary necklace identified in the developing canine retina was similar to those found in other types of motile and sensory cilia.

Animals↗