DNA Diseases

Human mitochondrial genome showing locations of disease-causing mutations. [Reproduced with permission from M.D. Brown and D.C. Wallace Molecular basis of mitochondrial DNA disease, J. Bioenerg. Biomembranes 26, TTi (1994).]... 

IgG leakage IgG leakage from serum into the nervous tissue can be used as a marker of altered vascular permeability Detection of IgG leakage can be used to determine BBB disruption in experimental models [17, 51, 52] as well as in humans [16-18,53] Model of HIV-1-associated nemocognitive disorder [25], stroke [33], epilepsy [30, 34, 35], infectious disease linked to herpes virus or HIV-1 [36], mucopolysaccharidoses [37], patients with mitochondrial DNA disease [38]... 

GLUTl fChronic alcohol intake [64], senescence-acceleration [65], AD [66], toxicity of methamphetamine [67], cortical cold injury [68], human brain injury [69], patients with mitochondrial DNA disease [39], epilepsy, ischemia, traumatic brain injury... 

CoUagen type IV fExperimental hematoma [75], stroke [84], subarachnoid hemorrhage [85], traiuna [86], bacterial meningitis [87], transient focal cerebral ischemia [88], brain irradiation [89], patients with mitochondrial DNA disease [38], cerebral cortex of HIV-1 patients [90]... 

Lax NZ, Pienaar IS, Reeve AK et al (2012) Microangiopathy in the cerebellum of patients with mitochondrial DNA disease. Brain 135 1736-1750... 

DNA sequence data have been used to investigate inherited diseases such as hemophilia and muscular dystrophy, and also in cancer research. 

Many human diseases are caused when certain proteins are either over- or underexpressed. Eor example, breast cancer can be induced by overexpressing certain cellular oncogenes within mammary tissue. To study the disease, researchers produce a line of transgenic mice that synthesize an abnormal amount of the same protein. This leads to symptoms of the disease in mice that are similar to what is found in humans. A protein can be overexpressed by inserting a DNA constmct with a strong promotor. Conversely, underexpression of a protein can be achieved by inserting a DNA constmct that makes antisense RNA. This latter blocks protein synthesis because the antisense RNA binds and inactivates the sense mRNA that codes for the protein. Once a line of mice is developed, treatments are studied in mice before these therapies are appHed to humans. 

Bleomycin sulfate is used alone or in combination with other antineoplastic dmgs. Using this DNA-cleaving dmg, disease-free (possibly cured) survivors of some cancers have been seen, especially with the use of bleomycin in multidmg regimens. General reviews of bleomycin (234,242—245) and its mechanism of action (246—249) are available. 

The use of agarose as an electrophoretic method is widespread (32—35). An example of its use is in the evaluation and typing of DNA both in forensics (see Forensic chemistry) and to study heritable diseases (36). Agarose electrophoresis is combined with other analytical tools such as Southern blotting, polymerase chain reaction, and fluorescence. The advantages of agarose electrophoresis are that it requires no additives or cross-linkers for polymerization, it is not hazardous, low concentration gels are relatively sturdy, it is inexpensive, and it can be combined with many other analytical methods. 

A mutagen is a chemical that can induce alterations in the DNA. Mutations occurring in germ cells are inheritable and may lead to genetic diseases. If mutations take place in somatic cells, carcinogenesis may be initiated. 

FIGURE 1.25 The virus life cycle. Viruses are mobile bits of genetic iuformatiou encapsulated in a protein coat. The genetic material can be either DNA or RNA. Once this genetic material gains entry to its host cell, it takes over the host machinery for macromolecular synthesis and subverts it to the synthesis of viral-specific nucleic acids and proteins. These virus components are then assembled into mature virus particles that are released from the cell. Often, this parasitic cycle of virus infection leads to cell death and disease. 

LDA, see Lithium diisopropylamide LDL, heart disease and, 1090-1091 Le Bel, Joseph Achille, 7-8 Leading strand, DNA replication and, 1107... 

Cancer is a serious malfunction of normal cell growth. In the years from 1950 through 1970, the major approach to treating this disease had been to target DNA and DNA precursors according to the hypothesis that rapidly dividing cells (cancer cells) are more susceptible to DNA toxicity... 

Viruses are small infectious agents composed of a nucleic acid genome (DNA or RNA) encased by structural proteins and in some cases a lipid envelope. They are the causative agents of a number of human infectious diseases, the most important for public health today being acquired immunodeficiency syndrome (AIDS), hepatitis, influenza, measles, and vituses causing diarrhoea (e.g., rotavirus). In addition, certain viruses contribute to the development of cancer. Antiviral drugs inhibit viral replication by specifically targeting viral enzymes or functions and are used to treat specific virus-associated diseases. 

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