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Biomedical subjects

T C White

Publications and source records attributed to T C White.

65 records · Page 4Linked to original sources

Clinico-histopathologic correlation of a successful glaucoma pump-shunt implant.

A 64-year-old diabetic man was treated for neovascular glaucoma with a pump-shunt implant (seton) after maximal medical therapy was unsuccessful. The seton, with supplemental agents, maintained the intraocular pressure (IOP) within a therapeutic range for 6 months, until the time of death from cardiac complications. Histopathologic evaluation of the eye showed the inlet of the seton in the periphery of the anterior chamber, not in contact with a coexisting anterior chamber intraocular lens (IOL). There was no fibrosis of the intracameral portion of the device. The tissue tract containing the silicon outlet tube extended from peripheral Descemet's membrane, through the sclera, to exit in the episcleral tissue over the posterior pars plana. Fibrous tissue originating from the episclera encased the external chambers of the seton. The internal contours of the fistulous tract, i.e., that portion adjacent to the seton, were smooth. There was no gross tissue hiatus at the exit port of the seton. The posterior wall of the fibrous capsule surrounding the seton in this region was diaphanous and immediately anterior to an area of cystic tissue comprising an equatorially placed bleb. The bleb was characterized by an irregular internal surface and a cystic cavity crossed by collagenous columns, suggesting it was the sub-Tenon's reservoir of aqueous. The success of the seton in this particular case may be due to a lack of fibrous reaction in the anterior chamber and the establishment of a stable filtering bleb in the equatorial region of the eye.

Anterior Chamber↗

RNA end-labeling and RNA ligase activities can produce a circular rRNA in whole cell extracts from trypanosomes.

We have found two enzymatic activities in whole cell extracts from Trypanosoma brucei; an end-labeling reaction involving a single uridine at the 3' end of ribosomal RNAs (rRNAs) and an RNA ligase activity joining 5' monophosphates to 3' hydroxyl groups. The RNA ligase acts upon one of the small rRNAs (180 nucleotides) from the trypanosome ribosomal repeat unit, forming a circular RNA. The specific circularization of this small rRNA is probably dependent on the secondary structure of the molecule and is not detectable in vivo.

Animals↗

Stable introduction of exogenous DNA into Trypanosoma brucei.

The lack of a homologous transformation system for trypanosomes is a serious handicap to the study of gene expression in these protozoans. Attempts to develop such a system have been complicated by the lack of suitable homologous vectors and ignorance of the requirements for mRNA synthesis which is discontinuous in trypanosomes. We have found that Trypanosoma congolense, a close relative of T. brucei, contains exceptionally small chromosomes, which can be isolated whole and distinguished from those of T. brucei by the presence of a unique satellite DNA. We show here that mini-chromosomes from T. congolense can be introduced into T. brucei by electroporation and detected by hybridisation with T. congolense satellite DNA. The introduced DNA can survive through several generations in the absence of any selective pressure. These results provide the basis for the development of a transformation system for trypanosomes.

Animals↗

Three small RNAs within the 10 kb trypanosome rRNA transcription unit are analogous to domain VII of other eukaryotic 28S rRNAs.

We have localized the six ribosomal RNAs (rRNAs) which encode the 28S rRNA region of Trypanosoma brucei. These six rRNAs include two large rRNAs, 28S alpha (approx. 1840 nt) and 28S beta (approx. 1570 nt), and four small rRNAs of approximate sizes 220, 180, 140 and 70 nt. Three of these four small rRNAs (180, 70 and 140) are found at the 3' end of the 28S rRNAs region. Sequence analysis of this area shows that these three small rRNAs encode Domain VII, the last domain of secondary structure in the 28S rRNAs of eukaryotes. Hybridization of labeled nascent RNA to the cloned repeat unit and S1 nuclease protection analysis of putative precursors show that transcription initiates approximately 1.2 kb upstream of the 18S rRNA and terminates after the last small rRNA (140) at the 3' end of the 28S rRNA region. Analysis of three putative rRNA precursors suggests that the small rRNAs are not processed from the primary transcript until after the usual processing of the 5.8S rRNA region.

Base Sequence↗

Alternative processing of sequences during macronuclear development in Tetrahymena thermophila.

DNA is eliminated during development of the somatic MACronucleus from the germinal MICronucleus in the ciliated protozoan, Tetrahymena thermophila. Facultatively persistent sequences are a class of sequences that persist in the MAC DNA of some cell lines but are eliminated from the MAC DNA of other cell lines. One cloned MAC fragment contains a persistent sequence as well as sequences normally retained in the MAC. When this cloned fragment was used to construct MAC restriction maps of this region in cell lines whose MAC DNAs do, or do not, contain the persistent sequence, extensive variation in the map flanking this region was observed. The different DNA rearrangements of this MIC segment are epigenetically determined during or soon after MAC development. Moreover, different rearrangements may occur among the 45 copies of this MIC segment as a MAC is formed, resulting in polymorphisms that are later resolved by phenotypic assortment.

Animals↗

Eliminated sequences with different copy numbers clustered in the micronuclear genome of Tetrahymena thermophila.

As the ciliated protozoan Tetrahymena thermophila develops a new macronucleus (MAC) from products of its micronucleus (MIC), several repetitive sequences are eliminated from the MAC genome. Four MIC DNA clones containing repetitive sequences that are eliminated from the MAC were obtained. One clone contains a representative from each of three families of eliminated sequences. One, present in 200-300 copies in the MIC, is almost completely eliminated from the MAC. A second, present in approximately 50 copies in the MIC, is scattered throughout the genome, although up to half of the family members examined could be localized to chromosome 2. Approximately one tenth of the members of this less repetitive family persist in the MAC while the rest are eliminated. The third type of eliminated sequence has three to four members, all of which are eliminated from the MAC. Three of the members are located on three of the five MIC chromosomes, and one could not be mapped. This sequence is clustered with the other two families of sequences in at least three of the four sites. All three types of eliminated sequences are found in similar arrangements in the MIC of several different inbred strains of T. thermophila.

Animals↗

Aqueous shunt implant surgery for refractory glaucoma.

The newer generation of aqueous shunt implant for glaucoma filtration surgery has increased our ability to manage more successfully glaucoma refractory or uncontrollable by medical therapy or standard surgical means. These clinical results suggest that surgery with such devices may even provide greater efficacy than standard filtration operations. The development of modern sophisticated device designs incorporating unidirectional valves has reduced complication and re-operation rates. Confidence in the use of these newer devices will increase as surgeons gain wider experience. Presently, some surgeons are considering aqueous shunt implant procedures before resorting to adjunctive antimetabolites to avoid scleral degeneration that may limit subsequent shunt surgery. Although glaucoma remains a disorder without a cure, the advent of aqueous shunt implants for glaucoma filtration surgery has greatly increased the prognosis for this visually threatening disorder.

Equipment Design↗