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Biomedical subjects

R McGuinness

Publications and source records attributed to R McGuinness.

At least 19 recordsLinked to original sources

A new-generation stable inducible packaging cell line for lentiviral vectors.

We have successfully generated and characterized a stable packaging cell line for HIV-1-based vectors. To allow safe production of vector, a minimal packaging construct carrying only the coding sequences of the HIV-1 gag-pol, tat, and rev genes was stably introduced into 293G cells under the control of a Tet(o) minimal promoter. 293G cells express the chimeric Tet(R)/VP16 trans-activator and contain a tetracycline-regulated vesicular stomatitis virus protein G (VSV-G) envelope gene. When the cells were grown in the presence of tetracycline the expression of both HIV-1-derived and VSV-derived packaging functions was suppressed. On induction, approximately 50 ng/ml/24 hr of Gag p24 equivalent of vector was obtained. After introduction of the transfer vector by serial infection, vector could be collected for several days with a transduction efficiency similar or superior to that of vector produced by transient transfection both for dividing and growth-arrested cells. The vector could be effectively concentrated to titers reaching 10(9) transducing units/ml and allowed for efficient delivery and stable expression of a GFP transgene in the mouse brain. The packaging cell line and all vector producer clones described here were shown to be free from replication-competent recombinants, and from recombinants between packaging and vector constructs that transfer the viral gag-pol genes. The packaging cell line and the assays developed will advance lentiviral vectors toward the stringent requirements of clinical applications.

Animals↗

T-cell killing of heterogenous tumor or viral targets with bispecific chimeric immune receptors.

We have previously described several novel chimeric immune receptors (CIRs) that redirect human T cells to kill malignant or HIV-infected cells. These CIRs comprise a cancer- or virus-specific ligand or single-chain antibody fused to the signaling domain of the T-cell receptor CD3-zeta subunit. Binding of the ligand- or antibody-based CIR to the target antigen (Ag) triggers T-cell-mediated cytolysis of the tumor- or virus-infected cell independent of target cell major histocompatibility complex class I expression. A new type of CIR was developed to mediate the lysis of cells that expressed one or more distinct viral or tumor Ags; three bispecific CIRs (BCIRs) were generated that recognized the carcinoembryonic Ag (CEA) and TAG-72 tumor Ags or, alternatively, distinct epitopes in the HIV envelope (HIVenv). T cells expressing the antitumoral Ag BCIR lysed both CEA- and TAG-72-expressing targets and did not kill Ag-negative targets or target cells expressing other members of the CEA family. Similarly, T cells expressing the anti-HIVenv BCIR lysed target cells expressing both the wild-type HIVenv and a mutant HIVenv that lacked the epitopes recognized by the monospecific CIRs. This approach permits the generation of T cells with a broader spectrum of activity capable of killing virus-infected cells and malignant cells and reduces the potential of progression of disease due to Ag loss variants.

Amino Acid Sequence↗

Atonic pupil.

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Aged↗

Alport's syndrome and the eye.

Alport's syndrome comprises hereditary deafness, nephritis and ocular abnormalities. The features of Alport's syndrome are illustrated by a family with Alport's syndrome and hereditary oesophageal leiomyomatosis. The evidence that Alport's syndrome is due to a widespread basement membrane disorder is noted. Treatment of anterior lenticonus, the principal ocular abnormality, by lensectomy and intraocular lens insertion is recommended.

Adult↗

Canthaxanthine (orobronze) retinopathy.

A 50-year-old white Australian male was found on routine examination to have small golden particles in the macular region of both eyes. A history of canthaxanthine (Orobronze) ingestion to produce skin bronzing was obtained.

Canthaxanthin↗

A review of Leiske style semi-flexible intraocular lenses 1981-1984.

A consecutive series of 205 patients had 237 intracapsular cataract extractions performed with the insertion of a semi-flexible intraocular lens in the period 1981-1983. The average follow-up period was 17.8 months; 87.0% of cases obtained a visual acuity of 6/12 or better after operation, compared with 80.6% of cases whose preoperative visual acuity was 6/36 or worse. Twenty-six eyes (11%) had clinical cystoid macular oedema at some stage after operation, and seven eyes (3%) had persistent cystoid macular oedema at final follow-up. Only one eye had a postoperative retinal detachment. Thirty eyes (14.1%) required treatment for elevated intraocular pressure at some time after operation.

Aged↗

Aplastic anemia.

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Adult↗

Timolol and dipivalyl epinephrine combination therapy.

Combination therapy with timolol 0.25% eye drops and dipivalyl epinephrine (DPE) 0.1% eye drops twice daily is an acceptable form of medication for both chronic simple glaucoma and ocular hypertension. A group of eighteen patients using this combination therapy have been followed up for a period of two years with satisfactory control of intraocular pressure in the majority of cases. An additive effect in lowering intraocular pressure when the two drugs were used in combination was confirmed. Two patients developed a sensitivity reaction to DPE and were able to continue on timolol alone. There was a slight rise in the intraocular pressure between the sixth and ninth months of therapy, but following this the mean intraocular pressure was remarkably stable. Patient acceptance of this twice daily regime was excellent and compliance with the drug therapy was also good.

Aged↗

The Prince of Wales Hospital prospective aphakic macular oedema study.

A two year study of one hundred and forty five cataract extractions showed a 38% incidence of post operative macular oedema. The leak had resolved in most cases by six months and the only factor of significance in the production of the oedema was preoperative hypertension. The likelihood of obtaining 6/6 vision postoperatively was much lessened in the presence of macular oedema.

Adult↗

Atrax robustus envenomation.

Two patients who developed massive pulmonary oedema, profound vasoconstriction and hypertension followed by hypotension after Atrax Robustus envenomation are described. The pulmonary oedema is due to increased pulmonary capillary membrane permeability which may be due to neurogenic or toxic causes. Use of artificial ventilation with high level PEEP, isoprenaline and high dose steroids allowed support of the patients during volume replacement with albumin. When the circulation was stable and airway frothing ceased, conventional dehydration therapy further improved lung function. Both patients were discharged well.

Adult↗