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Biomedical subjects

D Davidson

Publications and source records attributed to D Davidson.

At least 127 records · Page 7Linked to original sources

Shared sacrifice: the right message for America.

Is President Clinton naive to ask Americans to buy into "shared sacrifice"? Actually, shared sacrifice seems the right message for America in the 1990s, writes Dick Davidson, president of the AHA. In fact, he says, it's probably the only way we'll be able to repair our economy and our health care system.

Community-Institutional Relations↗

Defects of neuronal migration and the pathogenesis of cortical malformations are associated with Small eye (Sey) in the mouse, a point mutation at the Pax-6-locus.

The mouse Small eye (Sey) locus is situated on chromosome 2. Molecular analyses have shown that SeyNeu represents a point mutation leading to a splice site error and loss of the functional gene product. The Sey locus has been shown to be identical with the paired box (Pax)-6 gene, which contains paired-like and homoeobox domains and is a developmental control gene. Pax-6 expression occurs in many parts of the central nervous system during embryogenesis. Therefore, we may expect the Sey mutation to result in abnormal development of the central nervous system. The present study shows that Pax-6 mutation has a bimodal effect upon neurogenesis in mouse: it causes a delay of premigratory neurons in a stage-, region-, and gene-dose-dependent manner. Additionally, Sey mutation impairs axonal growth and differentiation. Neurons of the cortical plate cease differentiation on approximately day 16 of gestation and appear to have increased cohesion: their cytoplasm is swollen and vacuolated. These changes coincide both with reduced formation of axons and with the onset of vacuolar degeneration in existing axons, glial cells and radial glial fibers. Consequently, there is an impairment of the peripheral migration of putative neurons so that the neonatal lesion pattern of the neocortical roof becomes dominated by a broad spectrum of neuronal migration disorders.

Animals↗

Fine-needle aspiration biopsy in oral and maxillofacial surgery.

Fine-needle aspiration biopsy is a technique that is gaining great popularity in both surgical and nonsurgical specialties. Its accuracy, safety, and usefulness have been demonstrated repeatedly; however, its usefulness seems to have been overlooked by oral and maxillofacial surgeons. This technique has many advantages in the diagnosis of mass lesions, including ease of use, cost effectiveness, convenience, and accuracy. It lends itself well to oral and maxillofacial surgery.

Adolescent↗

Use of artificial sphincter to bowel segment using rectus muscle interposition.

The use of artificial urinary sphincter around the urethra or bladder neck for the management of urinary incontinence secondary to intrinsic urethral sphincter deficiency is now well accepted. However, its use around the bowel to serve as a sphincter in urinary pouches is still anecdotal. Its use in experimental models has been met with failure because of ischemic bowel necrosis at the cuff site. To obviate these difficulties, a new technique was devised using a flap of rectus muscle that acted as a cushion between the cuff and the bowel wall. Results in five dogs showed that bowel wall ischemia is avoided with cuff pressure of 51-60 cm applied constantly for four weeks while providing pressure to leak around the closed cuff with a pressure of 62-75 cm water. Further study is needed to confirm the long-term effect of this technique on the bowel wall and the ability of the sphincter to maintain continence.

Abdominal Muscles↗

Maternally transmitted partial direct tandem duplication of mitochondrial DNA associated with diabetes mellitus.

Mitochondrial DNA from a 38 year old male with diabetes mellitus and features of mitochondrial dysfunction was analysed and shown to include a population with a partial duplication. The partially duplicated mitochondrial DNA molecules were evident in both muscle and blood. The region of mitochondrial DNA duplicated includes the origin of heavy strand replication, but not the light strand origin. This patient has features in common with other cases of partial direct tandem duplications and with a family which was reported to harbour a 10.4 kb mtDNA deletion. Initial restriction enzyme analysis of our case produced results consistent with a partial deletion of mitochondrial DNA. This leads us to propose that the rarity of reports of partial mitochondrial DNA duplications may stem in part from the classification of such mutants as partial deletions.

Adult↗

Neutrophil chemotaxis to leukotriene B4 in vitro is decreased for the human neonate.

Leukotriene B4 (LTB4) is a product of arachidonic acid metabolism and a potent chemoattractant for adult polymorphonuclear leukocytes (PMN). LTB4 may be an important inflammatory mediator in neonatal lung disorders such as bronchopulmonary dysplasia, but neonatal PMN chemotaxis to LTB4 has not been studied. We compared total PMN migration and its components, chemotaxis and chemokinesis, to LTB4 in newborns and adults. PMN from healthy adults and umbilical blood of healthy, full-term newborns (n = 21 pairs) were incubated in a 48-well chemotaxis chamber using 10-microns thick polycarbonate membranes. Membranes with pore sizes of either 3 or 5 microns (diameter) were used to assess the influence of PMN deformability on chemotaxis. For both 3- and 5-microns filter pore sizes, total PMN migration increased in a dose-dependent manner from an LTB4 concentration of 10(-9) to 10(-6) M. The increase in total PMN migration was due entirely to chemotaxis (no chemokinesis) for newborns and adults. However, chemotaxis for the newborn was markedly attenuated, specifically, 14 and 24% of adult values at LTB4 concentrations of 10(-8) and 10(-7) M, respectively, with the 3-microns pore size. With the 5-microns filter pore size, newborn chemotaxis significantly increased to 40 and 49% of adult values at LTB4 concentrations of 10(-8) and 10(-7) M, respectively. We conclude that PMN chemotaxis to LTB4 in vitro is lower in newborns than in adults and part of this impairment may be caused by a decreased deformability of the newborn PMN.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The herpes simplex virus thymidine kinase gene promoter contains a novel thyroid hormone response element.

Thyroid hormone (T3) receptors (T3Rs) regulate transcription by binding to T3 response elements (TREs) located within promoter regions of T3-regulated genes. In rat pituitary GH4C1 cells, expression of a reporter containing herpes simplex virus thymidine kinase (TK) gene sequences (-105/+51) linked to the chloramphenicol acetyltransferase gene was stimulated 4- to 5-fold by T3. Linker scanning mutants of the TK promoter revealed that regions around -80 containing a CTF/NF-1 recognition sequence and around -10 are both required for regulation by T3. Endogenous T3Rs from GH4C1 cells labeled with [125I]T3 bound only to TK promoter DNA fragments containing the -10 region. The -22/-2 sequence (TK-TRE) contains half-sites oriented as an inverted repeat separated by 6 basepairs that are identical to and similar to an optimized TRE half-site. Purified chicken T3R alpha 1 forms apparent monomeric and dimeric complexes on the 32P-labeled TK-TRE, as found previously with an inverted repeat of the optimized TRE (TREp) with no basepair gap. T3 enhances the formation and alters the mobility of these complexes on both elements. When positioned up-stream of a heterologous promoter-chloramphenicol acetyltransferase reporter, the TK-TRE conferred T3 regulation by endogenous T3R in GH4C1 cells and by cotransfected chicken T3R alpha 1 in HeLa cells. The TK-TRE does not bind and is not activated by retinoic acid receptor. T3Rs and nuclear proteins from GH4C1, HeLa, and COS1 cells form heterodimers on the TK-TRE which differ in abundance and mobility from heterodimers formed on the TREp. The identification of a TRE in the TK promoter raises the possibility that T3R or related proteins may play important roles in regulating the life cycle of herpes simplex virus.

Animals↗