With the coming of a new disease eruption hitting the human population, molecular life scientists have been charged with the undertaking to clarify the molecular pathology of a new disease ( referred to as ‘Disease-A ‘ from now on ) utilizing attacks of molecular genetic sciences, genomics and proteomics to place, name and propose curative methods to develop a suited remedy. Patients affected with Disease-A are presented with flu-like symptoms followed by anemia, acute bone hurting and lassitude. Within 4-6 hebdomads, patients are presented with high febrilities and weight loss ; and after 6-12 months, patients die from timeserving infections caused by a badly impaired immune response. Clinical studies besides revealed extra information, with patients holding an elevated white cell count and extremely metastatic lymphoma of T-cell beginning. Disease-A is distributed equally throughout the population with no peculiar race or cultural group except for persons of Afro-Caribbean decent which are less affected. Disease-A is besides rare in homosexual males with a pronounced extremum incidence between ages 18-25.
The first diagnostic outgrowth of Disease-A, grippe, anemia, acute bone hurting and lassitude can be likened to a figure of blood related upsets like reaping hook cell anemia, Leukemia, Pernicious anemia, Hypercalcemia and a host of others. High febrilities and weight loss besides suggests Disease-A is blood related. Patients deceasing after 6-12 months of the disease owing to timeserving infections caused by a badly impaired immune response suggest that Disease-A compromises the patient ‘s immune system. This can besides be likened to a pathogen or virus infection like Human Immune Deficiency syndrome ( HIV ) , Severe Combined Immunodeficiency ( SCID ) , Human Cytomegalovirus, X-linked Agammaglobulinemia etc. The fast rate at which the disease progresses to human death besides suggests that the disease is acute in nature. Patients septic with Disease-A besides show to hold an elevated white cell count which extremely suggests that it is a blood disease and being a extremely metastatic lymphoma of T-cell beginning shows the disease is besides cancerous ( of lymphatic beginning ) . This makes Disease-A to be inclined towards an ague leukaemia. The pronounced extremum of incidence, 18-25 old ages, and disease rareness in non-sexually active kids suggests the disease is common to sexually goaded persons and is besides sexually transmitted. With an even distribution of Disease-A amongst bi-sexual and heterosexual communities, it goes on to back up the hypothesis of the disease being sexually transmitted and caused by an infection, most probably a viral infection. With the above suggestions, Disease-A looks to be a blood related upset induced by a viral infection which causes an immunodeficiency of lymphoid cells via the alterations to T-cell catching by sex or exchange of organic structure fluids.
Therefore the suggested mechanism of Disease-A is as follows. Patients get infected with the virus vertically from female parent to child by chest eating, horizontally by exchange of organic structure fluid, or by blood transfusion. This is in line with viral diseases. The virus attacks the T-cell lymphocytes precursors of the immune system and incorporates its Deoxyribonucleic acid into the host ‘s genome to ease its reproduction. This consequences in the apprehension and transmutation of T-cell lymphoblast which escapes programmed cell death, invariably divides and in bend increasing the white cell count most of which will be leukemic. The virus induces a mutant in the T-Cell taking to loss-of-function. The septic cells, now immortalised, additions in population, invade the bone marrow and herd the normal blood cells, cut downing their population. This brings about the symptoms of anemia, Flu, lassitude and bone hurting ; all which are associated with blood upsets. As the disease progresses with clip, the immune system is badly compromised and gives manner for timeserving infections like Pneumocystis pneumonia, Strongyloidiasis, Staphylococcus aureus, Pseudomonas aeruginosa and a assortment of Fungis, bacterial and viral infections etc. , of which patients die if non treated. However, half of the patients with the initial emergent symptoms retrieve which suggests a signifier of opposition to the virus infection encoded within their genome.
A figure of different techniques can be employed to prove the hypothesis. A complete blood count ( CBC ) can be used to prove for blood abnormalcies or infections. In this instance it will prove for anemia and elevated white blood count. The CBC findings will be confirmed utilizing peripheral blood vilification or blood movies. A decrease in ruddy blood cells and elevated white cell count will propose anemia and leukaemia severally. Bone marrow samples can besides be collected to happen the presence of leukemic cells by flow cytometry. Abnormal T-cells can be detected utilizing PCR-based trials ( Inverse PCR ) on lymphoid cells to test for the presence of the provirus DNA within the host genomic DNA. Blood serum or plasma can be screened for tumour markers via marker choice and the anticipation can be validated utilizing Real Time Polymerase Chain Reaction and an antibody-based check to supervise the viral burden. Chest X-ray can be used to seek for timeserving infections common to blood upsets like pneumonia, bone lesions and other related infections. Blood civilizations should be obtained to besides observe fever-causing infection like bacteriums, Fungis or virus. Genomes of patients who recovered should besides be screened to look into for natural fluctuations capable of confabulating opposition to the virus infection. This can be done by pyrosequencing or seeking for allelomorphic markers within a population of Disease-A affected patients and those who recovered without any ill-effects.
To name Disease-A, several serological trial can be adopted. Blood samples from the septic patients should be taken with the plasma screened to look into the presence of viral antibodies utilizing Enzyme-linked immunosorbent check ( ELISA ) . ELISA is an immunodiagnostic trial used to observe virus antibodies in blood samples/ serum, allergic reactions and diseases in worlds and animate beings ( Butler, 2000 ) . ELISA utilizes enzyme-conjugated antibodies, with antigen or antibodies bound to a solid support. It reports the quantitative finding of antibodies and steps alterations in enzyme activities involved in immune reactions ( Engvall and Perlmann, 1972 ) . This method can besides be used to observe works viruses ( Clark and Adams, 1977 ) . Consequences from ELISA can be confirmed by a simple western smudge and hybridised to a complementary DNA investigation to corroborate the presence of viral proteins within the septic patient serum sample. This is necessary because ELISA can give a false positive consequence for the virus antibody. To corroborate utilizing western blotting, the serum sample will be positive for the viral antibody. Another serological trial that can be used to name Disease-A is by indirect immunoflourescence technique. This technique uses the specific binding of antibodies to antigen to aim fluorescent dyes to specific marks in the cell. This method is preferred to direct immunofluorescence because of its specificity. This technique has been used to observe the per centum addition of leukocytes antibodies in patients with feverish transfusion reactions ( Verheugt et al, 2008 ) and monoclonal antibodies produced against the Dengue virus ( Henchal et al, 1982 ) . In utilizing this technique Disease-A will be diagnosed for the presence of the viral antibody in the septic patient blood serum.
To name suggested leukaemia, a bone marrow aspiration and biopsy ( BMAB ) can be used to corroborate leukemic cells. This method is used to name a figure of akin and non-blood related upsets like chronic lymphocytic leukaemia ( CLL ) , Hodgkin and Non-Hodgkin lymphoma, hairy cell leukemia multiple myeloma, thrombocytosis, leukocytosis, anemia, TB, Mycobacterium avium intracellulare ( MAI ) infections, histoplasmosis, leishmaniosis, and other fungous infections, nevertheless more suited techniques are available to name most of the disease mentioned. To name Disease-A by BMAB, bone marrow samples are taken from septic patient and biopsied. The consequence of the biopsy should be positive for a extremely metastatic lymphoma. A novel technique used to place disease biomarkers from a population of morbid and normal patients can besides be used as a diagnostic tool for Disease-A, called Surface-Enhanced Laser Desorption/Ionisation Time-of-Flight Mass Spectrometry ( SELDI-TOF MS ) ( Grizzle et al, 2003 ) . This technique can be used to bring forth protein look profiles from serum and clinical samples every bit good as biomarker designation for assorted malignant neoplastic diseases and diseases ( Tolson et al, 2004 ) . This powerful technique is besides used to analyze protein-protein and protein-DNA interaction. Proteomicss has been used to foretell fresh marks for malignant neoplastic disease therapy and drug opposition ( Hanash et al, 2002 ) . It has been reportedly used in biomarker designation and mark malignant neoplastic disease therapy in nephritic malignant neoplastic disease ( Tolson et al, 2004 ) , prostatic malignant neoplastic disease ( Grizzle et al, 2003 ) , acute leukaemia ( Hanash et al, 2002 ) , B-cell chronic lymphocytic leukaemia ( Voss et al, 2001 ) etc. This technique can besides be adopted to test for biomarkers in Disease-A in order to plan ‘drugable ‘ curative marks.
The first measure in healing therapy is to bring around identified timeserving infections with perennial drug intervention and antibiotics. Expression profiles utilizing proteomics have been used to place targeted therapy for some malignant neoplastic disease types. This method will besides be used to develop healing therapy for Disease-A. As described earlier, SELDI-TOF MS can be used to place high degrees of protein in morbid patient serum comparative to non-diseased patient. In a disease similar to Disease A, i.e. acute lymphoid leukaemia, high degrees of a polyprotein, oncoprotein 18 ( Op18 ) , was seen in morbid lymphoid cells compared to those of healthy lymphoid cells. Therefore it is suggested that suppressing Op18 look may infectively suppress leukemic cell proliferation ( Melhem et al, 1997 ) . Likewise, down modulating Op18 look inhibited tumorigenecity of leukemic cells in an immunodeficient mouse theoretical account ( Hanash et al, 2002 ) . This attack can be used as a curative drug mark for Disease-A by utilizing SELDI-TOF MS to place high look degrees of protein with the morbid patients and control.
Since the lymphoma was stubborn to conventional chemotherapy and radiation therapy in Disease-A, another healing therapy can be done by utilizing bone marrow organ transplant. As reported by Borg et Al. ( 2003 ) , allogeneic bone marrow organ transplant from a histocompatible Human T-cell lymphoblastic Virus 1 ( HTLV-1 ) negative giver to a HTLV-1 positive patient showed complete remittal and PCR revealed no grounds of the viral infection after 23 months. The consequence is similar for a leukemic upset, Philadelphia chromosome-positive ague lymphoblastic leukaemia, where the bone marrow organ transplant proved effectual as a curative method for lymphoblastic leukaemia ( Barrett et al, 1992 ) which is besides a similar disease to Disease-A. Therefore, bone marrow organ transplant from a healthy patient to a Disease-A patient can turn out effectual every bit long as they are histocompatible. Other bone marrow organ transplant techniques have besides been reported which can be adopted for Disease-A i.e. utilizing unrelated and related T-cell depleted bone marrow organ transplant ( Small et al, 1999 ) . The usage of allogeneic haematopoietic root cell organ transplant has been elucidated as an option to cram marrow organ transplant. This involves the transportation of haematopoietic root cells from the bone marrow or blood from a healthy person to a diseased person in the intervention of T-cell leukaemia ( Utsunomiya et al, 2001 ) .
Another therapy that could be developed to bring around Disease-A is cistron therapy. It involves utilizing DNA that encodes a functional cistron to replace the mutated cistron to supply intervention. This method though hazardous can be a signifier of healing therapy if used efficaciously. It uses viral vectors to convey the curative stuff into cells. This method has been used successfully in the intervention of malignant neoplastic disease harmonizing to Zhang et Al. ( 1996 ) . Viral vectors used for cistron therapy include adeno-associated virus, adenovirus, lentivirus and the most ideally used being the retrovirus. Other cistron therapies include small-interfering RNA cistron knockdown and RNA enzyme-directed cistron therapy ( Altman, 1993 ) .
Targeted drug therapy can besides be used as healing therapy as in the Acute Lymphoblastic Leukemia which is similar to Disease-A. The intervention uses drugs designed to recognize and kill lymphocyte cells without harming root cells. The monoclonal antibody, Alemtuzumab is used to aim mature lymph cell cells ( Enblad et al, 2004 ) . Alemtuzumab binds CD52, a protein found on mature lymph cells and more on transformed lymph cells, and becomes a mark for devastation. Other type of targeted drug therapy include interferon alpha, topoisomerase inhibitor, Retrovir plus interferon alpha, arsenic trioxide plus interferon alpha, encirclement of NF-KB and by monoclonal antibodies IL-2R receptors ( Taylor and Matsuoka, 2005 ) . In relation to being furnace lining, a nucleoside drug, Clofarabine, has been used as a healing therapy in leukaemia ( Jeha et al, 2004 ) which should besides use to Disease-A as the disease is suggested leukemic. In another survey, a combination of Clofarabine and Cytarabine ( ara-C ) has been used for stubborn acute leukaemia ( Faderl et al, 2005 ) . Another nucleoside drug Nelarabine is besides used for refractile T-cell malignance ( Kurtzberg et al, 2005 ) which is common to Disease-A.
Curative therapy can besides be developed If natural fluctuations are found within the population who recovered or who are seldom affected by Disease-A, in this instance Afro-Caribbean ‘s. This fluctuation can be engineered into septic Disease-A patients to confabulate opposition to the disease. This method has been reported by Perez et Al. ( 2008 ) in which a omission in the coding part of a chemokine receptor, CCR5, confers resistance to HIV-1 infection in homozygous bearers. Some human populations carry a natural mutant of this receptor and are immune to HIV-1 infection ( Huang et al, 1996 ) . This led to the usage of engineered Zinc finger nucleases to bring on a mutant in the CCR5 cistron in septic persons confabulating opposition to HIV-1 CD4+ T cells ( Perez et al, 2008 ) . This can be exploited if natural fluctuations are found in the non-affected Disease-A population.
In drumhead, persons infected with the unknown Disease-A were present with flu-like symptoms followed by anemia, acute bone hurting, lassitude, high febrilities and weight loss and after 6-12 months, died from timeserving infections caused by a badly impaired immune response. Clinical and laboratory probes revealed an elevate white cell count and a extremely metastatic lymphoma of T-cell beginning. Based on the symptoms and epidemiological surveies it was suggested that Disease-A was a blood related upset induced by a viral infection which causes an immunodeficiency of lymphoid cells via the alterations to T-cell catching by sex. The hypothesis was tested by making a complete blood count to determine infections doing the observed symptoms and a PCR-based trial to supervise the viral burden. A figure of diagnostic methods were outlined including serology trial, bone marrow biopsy and SELDI-TOF MS to determine leukemic cells and viral antibody. And eventually, a figure of healing therapies were highlighted ; bone marrow organ transplant, drug therapy and cistron therapy, to call a few.