Gene therapy: An updated overview on the promising success stories.

Gene therapy is a method of treatment of disease aimed at its molecular level. The progress of gene therapy, however, was as promising as it was tardy mainly due to the limitations in the resources and financial part of its development as well as owing to the rarity of most diseases it can offer its benefits to. The methods of gene therapy can vary depending on factors such as the physiology of tissue of interest, affinity of vectors to a certain type of cells, depth and accessibility of the tissue of interest, and size of the gene to be replaced or edited. The concept behind gene therapy has inspired scientists and clinicians alike leading to a rapid expansion of its clinical utility that has become so widespread to not only include diseases of monogenic origin, but also polygenic diseases, albeit not so commonly. This article delves into notable success stories of gene therapy which has been regarded as the beacon of medical novelty expected to blossom in the near future to provide a holistic, targeted, precise, and individualistic personalised-medicine as well as laying out the future hopes of gene therapy in the treatment of debilitating diseases such as solid tumours, AIDS, Tuberculosis, Diabetes Mellitus, psychiatric illnesses, which are still at a standstill, from a gene therapy point of view.

Influence of the nucleoid and the early stages of DNA replication on positioning the division site in Bacillus subtilis.

Although division site positioning in rod-shaped bacteria is generally believed to occur through the combined effect of nucleoid occlusion and the Min system, several lines of evidence suggest the existence of additional mechanisms. Studies using outgrown spores of Bacillus subtilis have shown that inhibiting the early stages of DNA replication, leading up to assembly of the replisome at oriC, influences Z ring positioning. Here we examine whether Z ring formation at midcell under various conditions of DNA replication inhibition is solely the result of relief of nucleoid occlusion. We show that midcell Z rings form preferentially over unreplicated nucleoids that have a bilobed morphology (lowering DNA concentration at midcell), whereas acentral Z rings form beside a single-lobed nucleoid. Remarkably however, when the DnaB replication initiation protein is inactivated midcell Z rings never form over bilobed nucleoids. Relieving nucleoid occlusion by deleting noc increased midcell Z ring frequency for all situations of DNA replication inhibition, however not to the same extent, with the DnaB-inactivated strain having the lowest frequency of midcell Z rings. We propose an additional mechanism for Z ring positioning in which the division site becomes increasingly potentiated for Z ring formation as initiation of replication is progressively completed.

Detection of simple mutations and polymorphisms in large genomic regions.

We have developed a novel technology that makes it possible to detect simple nucleotide polymorphisms directly within a sample of total genomic DNA. It allows, in a single Southern blot experiment, the determination of sequence identity of genomic regions with a combined length of hundreds of kilobases. This technology does not require PCR amplification of the target DNA regions, but exploits preparative size-fractionation of restriction-digested genomic DNA and a newly discovered property of the mismatch-specific endonuclease CEL I to cleave heteroduplex DNA with a very high specificity and sensitivity. We have used this technique to detect various simple mutations directly in the genomic DNA of isogenic pairs of recombinant Pseudomonas aeruginosa, Escherichia coli and Salmonella isolates. Also, by using a cosmid DNA library and genomic fractions as hybridization probes, we have compared total genomic DNA of two clinical P.aeruginosa clones isolated from the same patient, but exhibiting divergent phenotypes. The mutation scan correctly detected a GA insertion in the quorum-sensing regulator gene rhlR and, in addition, identified a novel intragenomic polymorphism in rrn operons, indicating very high stability of the bacterial genomes under natural non-mutator conditions.

Idiopathic cyclic thrombocytopenia of childhood.

Two children were found to have cyclic thrombocytopenia, recurring at regular intervals. Coagulation studies as well as immunologic evaluation did not reveal any abnormality. One of the patients continued to demonstrate the cyclic fluctuation in platelet counts despite corticosteroid therapy and showed no response to fresh frozen plasma infusion. One patient had been previously misdiagnosed as having idiopathic thrombocytopenic purpura (ITP), which might have caused problems if other therapies had been tried. The diagnosis of cyclic thrombocytopenia led to appropriate counseling and activity regulation.

Epidemiological study of an outbreak of infectious coryza on a poultry farm in Iraq.

This report deals with an outbreak of infectious coryza (IC) in a Badosh, Iraq, poultry farm in 1982. It appears to be the first published report of IC in Iraq, although claims of previous occurrence of the disease have been made.

Basal ganglia calcification on CT scanning in children with acute lymphocytic leukemia.

Calcification occurring in the basal ganglia in children with acute lymphocyte leukemia following therapy is uncommon and to the best of our knowledge has not been reported prior to therapy. Eleven cases of bilateral symmetrical calcification in the basal ganglia were noted in 2350 CT scans, two being in children with acute lymphocytic leukemia. In one of the two cases, calcification was present prior to therapy.

Hypercalcemia associated with neuroblastoma.

We studied two children with neuroblastoma in whom hypercalcemia developed as the initial manifestation in one and during the course of therapy in the other. Serum parathyroid hormone activity was elevated in the patient in whom the test for it was performed. Mithramycin controlled the hypercalcemia in one patient and tumor resection with radiation therapy and chemotherapy was sufficient for control of this complication in the other.

Massive sequestration crisis in sickle cell disease following ocular evisceration.

A case of an 11-year-old Negro female with SC disease who sustained right eye injury with development of a massive and fatal sequestration crisis following ocular evisceration was presented. The inherent danger of SC disease in relation to surgical procedures and general anesthesia was stressed and recommendations as to preoperative management of SC disease was briefly discussed.

Mumps uveitis complicating the course of acute leukemia.

A case of a nine-year-old child with acute lymphocytic leukemia in remission who developed infectious parotitis with uveitis was presented. Ocular complications of mumps have been briefly discussed and the differential diagnosis particularly in relationship to leukemia have been emphasized. The significance of depressed cellular immunity in the development of this complication was entertained.