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Biomedical subjects

Lawrence Lee

Publications and source records attributed to Lawrence Lee.

12 recordsLinked to original sources

Dynamics of retinal function after multiple photodynamic therapies in age-related macular degeneration: a report of cases.

PURPOSE: To monitor retinal function after multiple laser treatments by photodynamic therapy (PDT) with the multifocal electroretinogram (mfERG) in age-related macular degeneration (AMD). METHODS: Five eyes of five subjects with AMD were investigated before the first and 1 month after each of three PDT treatments. Function was assessed using the cone- and rod-mediated mfERG, high-contrast distance visual acuity, central visual fields and contrast sensitivity. For each subject the local first-order mfERG results before treatment were used as a template and fitted against the local post-treatment results (Matlab, Mathworks). RESULTS: We found transient reduction of the cone- and rod-mediated amplitudes between the first and second treatments but stable or improved mfERG function in four of five eyes for the cone-mediated mfERG and in all eyes for the rod-mediated mfERG after three treatments. Visual acuities and contrast sensitivities remained stable between treatments in four and two eyes respectively, whereas visual fields showed substantially higher mean defects in two subjects after all treatments. CONCLUSION: As found in previous studies of the cone-mediated mfERG after one PDT treatment, objective function was stabilized after multiple treatments in this case report. Similarly, although poor at baseline, rod-mediated function was not further compromised. Transiently reduced amplitudes after 1 month possibly reflected choroidal hypoperfusion. A larger sample size is needed to confirm if additional evaluation using electrophysiological criteria might be helpful in re-treatment decisions during PDT.

Aged↗

Choroidal osteoma: evidence of progression and decalcification over 20 years.

Choroidal osteoma is a rare, benign, ossifying tumour of the choroid of unknown aetiology. In contrast to other types of intraocular ossification, choroidal osteoma is found typically in young healthy females in the second or third decades of life with no history of systemic or ocular disease. Choroidal osteoma is a deep, pale yellow lesion with distinct geographic borders at the juxtapapillary or macular region, with branching 'spider' vessels on the surface of the tumour. These features should help differentiate choroidal osteoma from other types of intraocular tumour and the diagnosis can be confirmed with ultrasonography and computerised tomography. Here we report an initially unilateral case of choroidal osteoma, which decalcified over 20 years but during the same period the fellow eye also developed a choroidal osteoma to become a bilateral case. Despite the benign nature of the tumour, vision may be compromised by gradual atrophy of the overlying retina, serous retinal detachment, accumulation of sub-retinal fluid and sub-retinal haemorrhage associated with choroidal neovascularisation. Frequent examinations are recommended for patients with choroidal osteoma, for early detection of a subretinal neovascular membrane and potential treatment with laser photocoagulation.

Adult↗

A surface loop of the potato leafroll virus coat protein is involved in virion assembly, systemic movement, and aphid transmission.

Two acidic domains of the Potato leafroll virus (PLRV) coat protein, separated by 55 amino acids and predicted to be adjacent surface features on the virion, were the focus of a mutational analysis. Eleven site-directed mutants were generated from a cloned infectious cDNA of PLRV and delivered to plants by Agrobacterium-mediated mechanical inoculation. Alanine substitutions of any of the three amino acids of the sequence EWH (amino acids 170 to 172) or of D177 disrupted the ability of the coat protein to assemble stable particles and the ability of the viral RNA to move systemically in four host plant species. Alanine substitution of E109, D173, or E176 reduced the accumulation of virus in agrobacterium-infiltrated tissues, the efficiency of systemic infection, and the efficiency of aphid transmission relative to wild-type virus, but the mutations did not affect virion stability. A structural model of the PLRV capsid predicted that the amino acids critical for virion assembly were located within a depression at the center of a coat protein trimer. The other amino acids that affected plant infection and/or aphid transmission were predicted to be located around the perimeter of the depression. PLRV virions play key roles in phloem-limited virus movement in plant hosts as well as in transport and persistence in the aphid vectors. These results identified amino acid residues in a surface-oriented loop of the coat protein that are critical for virus assembly and stability, systemic infection of plants, and movement of virus through aphid vectors.

Animals↗

Evolving options in the management of esophageal perforation.

Esophageal perforation remains a devastating event that is difficult to diagnose and manage. The majority of injuries are iatrogenic and the increasing use of endoscopic procedures can be expected to lead to an even higher incidence of esophageal perforation in coming years. Accurate diagnosis and effective treatment depend on early recognition of clinical features and accurate interpretation of diagnostic imaging. Outcome is determined by the cause and location of the injury, the presence of concomitant esophageal disease, and the interval between perforation and initiation of therapy. The overall mortality associated with esophageal perforation can approach 20%, and delay in treatment of more than 24 hours after perforation can result in a doubling of mortality. Surgical primary repair, with or without reinforcement, is the most successful treatment option in the management of esophageal perforation and reduces mortality by 50% to 70% compared with other interventional therapies.

Esophageal Perforation↗

Nanophthalmic cataract extraction.

Nanophthalmos is a rare ophthalmic condition with potential sight-threatening complications. In addition, nanophthalmic eyes have a high incidence of intraoperative and postoperative complications, including uveal effusion and retinal detachment. Prophylactic measures to prevent these complications may be used. The case is presented where cataract extraction for a nanophthalmic eye was performed from a posterior approach in combination with a pars plana vitrectomy and gas procedure. To the authors' knowledge, this method of cataract extraction has not been reported before for this condition.

Cataract↗

Large-scale identification of genes required for full virulence of Staphylococcus aureus.

Gene products required for in vivo growth and survival of microbial pathogens comprise a unique functional class and may represent new targets for antimicrobial chemotherapy, vaccine construction, or diagnostics. Although some factors governing Staphylococcus aureus pathogenicity have been identified and studied, a comprehensive genomic analysis of virulence functions will be a prerequisite for developing a global understanding of interactions between this pathogen and its human host. In this study, we describe a genetic screening strategy and demonstrate its use in screening a collection of 6,300 S. aureus insertion mutants for virulence attenuation in a murine model of systemic infection. Ninety-five attenuated mutants were identified, reassembled into new pools, and rescreened using the same murine model. This effort identified 24 highly attenuated mutants, each of which was further characterized for virulence attenuation in vivo and for growth phenotypes in vitro. Mutants were recovered in numbers up to 1,200-fold less than wild type in the spleens of systemically infected animals and up to 4,000-fold less than wild type in localized abscess infections. Genetic analysis of the mutants identified insertions in 23 unique genes. The largest gene classes represented by these mutants encoded enzymes involved in small-molecule biosynthesis and cell surface transmembrane proteins involved in small-molecule binding and transport. Additionally, three insertions defined two histidine kinase sensor-response regulator gene pairs important for S. aureus in vivo survival. Our findings extend the understanding of pathogenic mechanisms employed by S. aureus to ensure its successful growth and survival in vivo. Many of the gene products we have identified represent attractive new targets for antibacterial chemotherapy.

Animals↗

Host-dependent requirement for the Potato leafroll virus 17-kda protein in virus movement.

The requirement for the 17-kDa protein (P17) of Potato leafroll virus (PLRV) in virus movement was investigated in four plant species: potato (Solanum tuberosum), Physalis floridana, Nicotiana benthamiana, and N. clevelandii. Two PLRV P17 mutants were characterized, one that does not translate the P17 and another that expresses a P17 missing the first four amino acids. The P17 mutants were able to replicate and accumulate in agroinoculated leaves of potato and P. floridana, but they were unable to move into vascular tissues and initiate a systemic infection in these plants. In contrast, the P17 mutants were able to spread systemically from inoculated leaves in both Nicotiana spp., although the efficiency of infection was reduced relative to wild-type PLRV. Examination of virus distribution in N. benthamiana plants using tissue immunoblotting techniques revealed that the wild-type PLRV and P17 mutants followed a similar movement pathway out of the inoculated leaves. Virus first moved upward to the apical tissues and then downward. The P17 mutants, however, infected fewer phloem-associated cells, were slower than wild-type PLRV in moving out of the inoculated tissue and into apical tissues, and were unable to infect any mature leaves present on the plant at the time of inoculation.

Amino Acid Sequence↗