Proton-beam irradiation of subfoveal choroidal neovascular membranes in presumed ocular histoplasmosis syndrome: a case report.

BACKGROUND: Presumed ocular histoplasmosis syndrome (POHS) refers to a choroidopathy that is characterized by the presence of multiple peripheral atrophic chorioretinal scars, peri-papillary atrophy, and choroidal neovascular membranes (CNVM), usually in or adjacent to the fovea. In the United States, POHS is an important cause of loss of central visual acuity in patients between the ages of 20 and 50 years. A number of treatment options for subfoveal and juxtafoveal CNVMs in POHS have been under investigation, including laser photocoagulation, surgical excision of the CNVM, and radiation therapy. CASE REPORT: A 28-year-old women was referred to our office reporting decreased depth perception and finger-counting vision in the right eye for the duration of 1 month. A diagnosis of POHS with subfoveal CNVM was made and the patient was referred for an experimental protocol of proton-beam irradiation. Four months after her initial visit, the patient returned, reporting blurry vision with a blind spot in her left eye. A subfoveal CNVM in the left eye was subsequently treated with irradiation as well. Seven months after the initial treatment, visual acuities were 20/20 in each treated eye. CONCLUSION: Although is currently an experimental procedure, proton-beam irradiation appears to be a promising treatment for subfoveal CNVM in patients with POHS.

Co-packaging of non-vector RNAs generates replication-defective retroviral vector particles: a novel approach for blocking retrovirus replication.

A Moloney murine leukemia virus (MoMuLV)-derived packaging retroviral vector, pUCMoTN-PR3, was previously developed in which the packaging (psi) signal was cloned within the 5'-long terminal repeat (LTR) U3-r and U5 sequences. The MoTN-PR3 vector particles released from a transfected packaging cell line contain RNAs with r-psi-U5 sequences at the 5'-end and U3-r sequences at the 3'-end. Upon infection, these vector particles can efficiently transduce the neomycin phosphotransferase (neo) gene to the target cells. The structure of the proviral DNA synthesized in these cells was shown to contain modified 5'- and 3'-LTRs with U3-r-psi-U5 sequences, indicating that this vector can undergo reverse transcription and integration. Analysis of psi signal-containing RNAs revealed that in addition to vector RNA transcribed from the MoMuLV 5'-LTR promoter, readthrough neo RNA transcribed from the internal herpes simplex virus (HSV) thymidine kinase (tk) promoter and cellular RNAs transcribed from the MoMuLV 3'-LTR promoter are produced. Of these, the downstream cellular RNAs are also packaged within the vector particles. These vector particles containing the vector and non-vector RNAs carrying the MoMuLV psi signal are non-infectious. It is proposed that intracellular expression of packageable non-viral RNAs may represent an effective strategy for inhibiting animal and plant virus replication.

Fitting characteristics of 1-day and 14-day Acuvue disposable contact lenses.

The fitting characteristics of 1-day Acuvue disposable soft contact lenses (SCLs) [base curve (BC) 9.0 mm, diameter 14.2 mm] and 14-day Acuvue disposable SCLa (BC 8.8 mm, diameter 14.0 mm) were evaluated and compared with respect to lens centration and post-blink movement in primary gaze and in upgaze. In this double-blind study 25 successful daily wearers of either the 1-day lens or the 14-day lens with the same parameters were randomly fit with three 1-day lenses and three 14-day lenses for a total of 6 lenses per eye. The lene fit was evaluated 5 min after insertion. Lens centration was assessed by measuring temporal, nasal, superior and inferior limbal coverage, and then comparing the net horizontal centration (temporal minus nasal coverage) and the net vertical centration (superior minus inferior coverage) of the 1-day and 14-day lenses. There was no significant difference between the two lenses in terms of temporal, superior, and inferior limbal coverage (p > 0.05). However, the 1-day lens showed statistically more nasal coverage (p < 0.05). No statistically significant difference in movement or in horizontal and vertical differences in centration were found (p > 0.05). Although our findings indicate a subtle statistical difference in fitting characteristics, clinically the two lenses should provide similar fits.

The development and testing of retroviral vectors expressing trans-dominant mutants of HIV-1 proteins to confer anti-HIV-1 resistance.

Trans-dominant mutants of human immunodeficiency virus type 1 (HIV-1) Tat and Rev are attractive candidates for use in gene therapy in the treatment of HIV-1 infections because both are essential for viral replication. Retroviral vectors were constructed to allow either Tat-inducible or Tat- and Rev-inducible expression of trans-dominant mutants of Tat and Rev. These vectors were used to infect a human CD4+ lymphocyte-derived cell line, MT4. To determine the efficacy of various Tat and Rev mutants in inhibiting HIV-1 multiplication, MT4 cells containing mutant-expressing constructs were infected with HIV-1, and the amount of HIV-1 released in the culture medium was measured for up to 30 days. A high level of resistance was observed in cells expressing the double tat/rev mutant in a Tat-inducible manner.

Resistance to human immunodeficiency virus type 1 (HIV-1) infection in human CD4+ lymphocyte-derived cell lines conferred by using retroviral vectors expressing an HIV-1 RNA-specific ribozyme.

Toward gene therapy for the treatment of human immunodeficiency virus type 1 (HIV-1) infections in AIDS, Moloney murine leukemia virus-derived retroviral vectors were engineered to allow constitutive and tat-inducible expression of an HIV-1 5' leader sequence-specific ribozyme (Rz1). These vectors were used to infect the human CD4+ lymphocyte-derived MT4 cell line. The stable MT4 transformants expressing an HIV-1 RNA-specific ribozyme, under the control of the herpes simplex virus thymidine kinase (tk) promoter, were found to be somewhat resistant to HIV-1 infection as virus production was delayed. In cells allowing ribozyme expression under control of the simian virus 40 or cytomegalovirus promoter, the rate of HIV-1 multiplication was slightly decreased, and virus production was delayed by about 14 days. The highest level of resistance to HIV-1 infection was observed in MT4 cells transformed with a vector containing a fusion tk-TAR (trans activation-responsive) promoter to allow ribozyme expression in a constitutive and tat-inducible manner; no HIV-1 production was observed 22 days after infection of these cells. These results indicate that retroviral vectors expressing HIV-1 RNA-specific ribozymes can be used to confer resistance to HIV-1 infection.