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Biomedical subjects

W J Green

Publications and source records attributed to W J Green.

16 recordsLinked to original sources

An integrated genetic and physical map of the 650-kb region containing the congenital polycystic kidney (cpk) locus on mouse chromosome 12.

Mice homozygous for the congenital polycystic kidney (cpk) mutation develop a rapidly progressive form of polycystic kidney disease. We report an integrated genetic and physical map of the 650-kb region containing the cpk locus and the exclusion of Rrm2 and Idb2 as candidate cpk genes. Our study establishes the requisite foundation for positional cloning of the cpk gene.

Animals↗

Germline and somatic loss of function of the mouse cpk gene causes biliary ductal pathology that is genetically modulated.

The mouse cpk mutation is the most extensively characterized murine model of polycystic kidney disease (PKD) and closely resembles human autosomal recessive PKD (ARPKD), with the exception that B6-cpk/cpk homozygotes do not express the biliary ductal plate malformation (DPM) lesion. However, homozygous mutants from outcrosses to other strains, e.g. DBA/2J (D2), CD-1, BALB/c and Mus mus castaneus (CAST), express the DPM. The current study was designed: (i) to characterize the cpk-associated biliary disease in affected F(2) homozygotes from intercrosses with either CAST or D2; and (ii) to evaluate focal biliary cysts identified in heterozygotes from a D2-cpk congenic strain. We found that all F(2) cpk/cpk pups expressed both the typical renal cystic disease and the DPM. The DPM severity, assessed using semi-quantitative histopathological analysis, was markedly variable in these F(2) progeny. We found no correlation between the severity of the DPM and the renal cystic disease in either F(2) cohort. In addition, we identified focal cysts, apparently of biliary origin, in the livers of both aged D2-+/cpk and F(1) heterozygotes. Genetic analysis demonstrated loss of heterozygosity at the cpk interval and supports a loss-of-function model for biliary cysts. We conclude that the cpk allele contains an inactivating mutation which disrupts tubulo-epithelial differentiation in the kidney and biliary tract. Expression of the biliary lesion is modulated by genetic background, and the specific biliary phenotype is determined by whether loss of function of the cpk gene occurs as a germline or a somatic event.

Animals↗

Spatial mapping of polarized light transmission in the central rabbit cornea.

In this paper polarized light transmission measurements are made under conditions that closely approximate the physiological state in order to probe lamellar structure in the central cornea of New Zealand white rabbits. The results are interpreted with the aid of a newly developed theory (published elsewhere) in which the cornea is modeled as stacked birefringent layers corresponding to the lamellae. The theory enables predictions of the statistical properties of lamellar ordering based on characteristics of the transmission of polarized light. The experimental results are consistent with a structure in which a number of lamellae have a fixed azimuthal orientation (i.e. about an axis normal to the corneal surface), whereas the remainder are essentially randomly oriented. Comparisons with the theoretical predictions are consistent with a model in which the preferred direction in the apical region of the cornea does not vary significantly among rabbits; and the preferred lamellar orientation direction determined for the population measured here is very close to that suggested in previous experiments on a smaller number of rabbits. Mapping experiments using a new goniometric holder showed that the preferential order at the apical region is closely preserved throughout the central approximately 4 mm diameter optical zone in individual corneas.

Animals↗

The mechanism of lamellar-to-inverted hexagonal phase transitions: a study using temperature-jump cryo-electron microscopy.

The lamellar/inverted hexagonal (L alpha/HII) phase transition can be very fast, despite the drastic change in the topology of the lipid/water interfaces. The first structures to form in this transition may be similar to those that mediate membrane fusion in many lipid systems. To study the transition mechanism and other dynamic phenomena in membrane dispersions, we constructed an apparatus to rapidly trigger the transition and then vitrify the specimens to preserve the structure of transient intermediates. The apparatus applies millisecond-long temperature jumps of variable size to aqueous dispersions of lipids on electron microscope grids at times 9-16 ms before specimen vitrification. The vitrified specimens are then examined by cryo-transmission electron microscopy. Dispersions of egg phosphatidylethanolamine completed the transition within 9 ms when superheated by 20 K. Similar transition times have been observed in dioleoylphosphatidylethanolamine via time-resolved x-ray diffraction. N-monomethylated dioleoylphosphatidylethanolamine dispersions superheated to lesser extent exhibited slower transitions and more complex morphology. The structure of the first intermediates to form in the transition process could not be determined, probably because the intermediates are labile on the time scale of sample cooling and vitrification (< 1 ms) and because of the poor contrast developed by some of these small structures. However, the results are more compatible with a transition mechanism based on "stalk" intermediates than a mechanism involving inverted micellar intermediates. Temperature-jump cryo-transmission electron microscopy should be useful in studying dynamic phenomena in biomembranes, large protein complexes, and other colloidal dispersions. It should be especially helpful in studying the mechanism of protein-induced membrane fusion.

Biophysical Phenomena↗

Metal dynamics in Lake Vanda (Wright Valley, Antarctica).

Data are reported for Mn, Fe, Co, Ni, Cu and Cd in the Onyx River, and for Mn, Co, Ni, Cu and Cd in Lake Vanda, a closed-basin Antarctic lake. Oxic water concentrations for Co, Ni, Cu and Cd were quite low and approximate pelagic ocean values. Scavenging of these metals by sinking particles is strongly indicated. Deep-lake profiles reveal a sharp peak in the concentrations of Mn, Fe and Co at the oxic-anoxic boundary at 60 m. Maxima for Ni, Cu and Cd occur higher in the water column, in the vicinity of a Mn submaximum, suggesting early release of these metals from sinking manganese oxide-coated particles. A rough steady-state model leads to the conclusion that there is a large downward flux of Mn into the deep lake and that this flux is sufficient to explain the annual loss of Co, Ni, Cu and Cd. A pronounced geochemical separation between Fe and Mn apparently occurs in this system--Fe being best lost in near-shore environments and Mn being lost in deeper waters. Comparison of metal residence times in Lake Vanda with those in the oceans shows that in both systems Mn, Fe and Co are much more reactive than Ni, Cu and Cd. Energetically favorable inclusion of the more highly charged metals, Mn(IV), Fe(III) and Co(III), into oxide-based lattices is a plausible explanation.

Antarctic Regions↗

Fasting motor activity occurs during a day of normal meals in healthy subjects.

Using a radiotelemetric technique of pressure recording which did not interfere with normal feeding, jejunal motor activity was recorded in seven healthy human subjects, who were given three hospital meals during the course of a day, and allowed ad libitum supplementary snacks. Fasting motor activity was detected during the day in five subjects, and, although its occurrence was very variable, tended to occur shortly before the next meal.

Adult↗

Normal patterns of human upper small bowel motor activity recorded by prolonged radiotelemetry.

In order to characterise human interdigestive cyclical motor activity, and its interruption by food, jejunal pressure changes in healthy volunteers were recorded continuously for 24 hours, using an ingested pressure-sensitive radiotelemetry capsule tethered at the duodenojejunal flexure. In 20 studies, the subjects fasted throughout; in another 20 studies they received a single standard meal. Using this technique, fasting motor complexes were easily detected. There was considerable variation in interdigestive cycle duration and in the interruption caused by food. The data were not normally distributed. The study indicates that any descriptions of 'atypical' jejunal motility patterns must take into account the wide variations seen in health, before they can be regarded as representing dysfunction or disease.

Adult↗

Keynote address.

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Delivery of Health Care↗

Bronchial arteriography and embolotherapy for hemoptysis in patients with cystic fibrosis.

Bronchial arteriography and embolotherapy were performed to control hemoptysis in 11 patients with advanced stages of cystic fibrosis. Two patients suffered massive, 1 moderate, and 8 mild but recurrent hemoptysis. The embolization procedures were performed with Gelfoam, Ivalon, and coils in one to four separate procedures. Altogether, 19 of 20 procedures were successful, with follow-up periods ranging from 9 months to 8 years. No serious complications were encountered except for one femoral artery pseudoaneurysm which required surgical repair. Rapid digital subtraction angiography and "roadmapping" were considered helpful in avoiding the complication of reflux embolization and expediting the procedures. Bronchial embolization is a life-saving procedure for severe hemoptysis in patients with cystic fibrosis and is considered safe enough to include the indications of moderate and mild/recurrent hemoptysis to improve the quality of life in these patients.

Adolescent↗