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Biomedical subjects

B Salomon

Publications and source records attributed to B Salomon.

17 recordsLinked to original sources

Expression of a Tat-inducible herpes simplex virus-thymidine kinase gene protects acyclovir-treated CD4 cells from HIV-1 spread by conditional suicide and inhibition of reverse transcription.

Cellular expression of the herpes simplex virus type 1 thymidine kinase (HSV1-TK) gene promotes cell death in the presence of specific nucleoside analog substrates such as acyclovir (ACV). We have reported that lymphoid CD4+ cells harboring an HSV1-TK gene, under the transcriptional control of the HIV-1 long terminal repeat (HUT-TK), are completely protected from HIV-1 spread in the presence of 10 microM ACV. In this report we clarify the efficiency, generality, and mechanism of this protective effect. We show that the protection from HIV-1 spread in HUT-TK cells obtains from both an inhibition of HIV reverse transcription by ACV metabolites and an HIV-induced and ACV-dependent cell killing. We also demonstrate that monocytic cells harboring the HIV-1-inducible HSV1-TK gene are protected from HIV spread in the presence of ACV. These observations facilitate the design of therapeutic strategies to limit HIV replication based on HSV1-TK expression.

Acyclovir

A truncated herpes simplex virus thymidine kinase phosphorylates thymidine and nucleoside analogs and does not cause sterility in transgenic mice.

Dividing eukaryotic cells expressing the herpes simplex virus type 1 thymidine kinase (TK) gene are sensitive to the cytotoxic effect of nucleoside analogs such as acyclovir or ganciclovir (GCV). Transgenic mice with cell-targeted expression of this conditional toxin have been used to create animals with temporally controlled cell-specific ablation. In these animal models, which allow the study of the physiological importance of a cell type, males are sterile. In this study, we showed that this phenomenon is due to testis-specific high-level expression of short TK transcripts initiated mainly upstream of the second internal ATG of the TK gene. This expression is DNA methylation independent. To obtain a suicide gene that does not cause male infertility, we generated and analyzed the properties of a truncated TK (delta TK) lacking the sequences upstream of the second ATG. We showed that when expressed at sufficient levels, the functional properties of delta TK are similar to those of TK in terms of thymidine or GCV phosphorylation. This translated into a similar GCV-dependent toxicity for delta TK- or TK-expressing cells, both in vitro and in transgenic mice. However, delta TK behaved differently from TK in two ways. First, it did not cause sterility in delta TK transgenic males. Second, low-level delta TK RNA expression did not confer sensitivity to GCV. The uses of delta TK in cell-specific ablation in transgenic mice and in gene therapy are discussed.

Animals

Performance of the dot visual acuity test with uncorrected ametropia resulting in target blur.

The dot visual acuity test is used to test the acuity of children between the ages of 2 and 4 years who do not respond to the tumbling E test. Because the test involves the detection of a black dot on a white background it is appropriate to ask if the detection threshold is lowered artificially in the presence of target blur. Twenty-one children (42 eyes) were used in the study. Refractive errors were fully corrected and each subject's lag of accommodation was measured. A monotonic decrease in acuity was found with increasing amounts of optical blur. The explanation for the decreased acuity is found in the reduced retinal image contrast of the blurred target.

Accommodation, Ocular

Cavernous sinus thrombosis in two Papua New Guineans.

Bilateral cavernous sinus thrombosis developed following minor forehead abrasions in two adult Melanesians in Papua New Guinea. In both cases diagnosis and the institution of appropriate treatment were delayed. The first patient died but the second survived with residual 6th cranial nerve palsy. Whenever this condition is suspected, because of the high case fatality rate, high-dose, intravenous antibiotic treatment which should include an agent effective against penicillinresistant staphylococci should be commenced without delay pending further investigation.

Adolescent

Donovanosis (granuloma inguinale) with vulval pseudo-elephantiasis.

A 24 year old Melanesian female from the Eastern Highlands of Papua New Guinea presented with chronic painless ulcers of the external genitalia, anus and thighs of many years' duration and marked left labial hypertrophy for one year. Scrapings from the ulcers contained large foamy mononuclear cells in which Donovan bodies were demonstrated. The ulcers responded to tetracycline therapy however she absconded after three weeks before surgical correction of the labial pseudo-elephantiasis could be carried out. Vulval pseudo elephantiasis of the magnitude present in this case is rarely seen in Papua New Guinea.

Adult

[Diagram for the prognosis of cephalo-pelvic disproportions. Application in 300 cases of pelvic contraction].

The authors using the information obtained by X-ray pelvimetry and ultrasound cephalometry in 300 cases of contracted pelves, suggest a diagram of cephalo-pelvic disproportion that can be used in the great majority of cases of contracted pelves. It is not applicable to those where there is significant deformation of the middle strait or an abnormality of presentation. It is divided into three zones: 1. A superior zone, favourable, into which the majority (60%) of cases of contracted pelvis fit. The risk of a serious dystocia during delivery is so small (less than 2%) that it can be considered scarcely different from those found in women with a normal pelvis. 2. An intermediate zone into which 24% of cases of contracted pelvis fit where the prognosis is uncertain. The labour should be considered as an "at risk" labour and a trial of labour conducted. 3. A lower zone into which 16% of the cases fit and which consists of two categories: --those in which the biparietal diameter is equal to or less than 90 mm. Prophylactic caesarean section should be avoided in these cases where disproportion is rare and where there is a risk of delivering a premature infant: and --those more numerous (9 out of 10) where the biparietal diameter is more than 90 mm and where, unless there is a clinically definitely favourable prognosis, it is justifiable to carry out prophylactic caesarean section. If this line is followed: one can avoid a large number of trials of labour, all of which are inconvenient and some of which are dangerous for the child; few unnecessary caesarean sections are carried out.

Adult