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Amer.RegistryofPathology 14th St. NW and Alaska Ave.,Washington D.C. 20306-6000; (202) 782-2143 phone, 782-4567 fax. Nonprofit private organization established by an act of Congress and affiliated with AFIP. Assists AFIP with its case consultative, educational, and research work by providing support staff and other resources.

Applied Genetics, Inc. 205 Buffalo Ave., Freeport NY 11520; phone (516) 868-9026, fax 868-9143. Biotechnology firm manufacturing an experimental skin lotion that may increase the resistance to UV of XP patients' skin surface, by causing more rapid repair of UV damaged DNA in skin surface cells.

ARP Abbreviation for American Registry of Pathology

ArmedForcesInstit.ofPathology 14th St. NW and Alaska Ave., Washington DC 20306-6000; (202) 782-7100 phone, 782-7164 fax. US federal building with over 100 pathologists trained in numerous subspecialties, whose work includes review of other pathologists' difficult cases, education (courses, literature, and study sets), and research on human and veterinary disease. It might be described as the "National Institute of Pathology" that for historical reasons is affiliated with the Department of Defense rather than with Health and Human Services.

Assay Laboratory test.

Ataxia telangiectasia Rare genetic disease in which there is abnormal sensitivity to X-rays, deficient repair of X-ray damage to DNA, immune deficiency, and extremely high rate of cancers of white blood cells.

Autoradiography Process in which a specimen is coated with a radioactive emulsion to detect the presence of radioactive material such as tritium using production of silver grains that can be seen under a microscope.

Autosomal recessive Condition in which genetic disease is present if both copies of a particular gene, present on chromosomes other than those used to determine a person's sex, are abnormal.

Beaker Cylindrical container used in laboratories.

Biopsy Small piece of tissue removed by a clinician e.g., skin biopsy removed by dermatologist for use in preparing skin fibroblast culture for CS or XP testing.

Buffer Solution with stable acidity or alkalinity.

Calcification Deposit of bone-like calcium containing material.

Carcinoma Cancer of cells lining surfaces of the body.

Carcinoma, Basal cell Common form of skin cancer, which grows but remains localized.

Carcinoma, Squamous cell Common form of cancer. When present in skin, it grows but remains localized.

Cataracts Abnormal eye condition in which there is clouding of the lens that allows the eye to focus. This causes poor vision or even blindness.

Cell The basic unit of life, generally about 1/1,000 inch in size in the case of "eukaryotic" cells from plants and animals in which there is a nucleus and cytoplasm. There are dozens of varieties of human cells with different specialized functions e.g., fibroblasts secrete collagen, which makes skin and other tissues tougher, while white blood cells fight infection and muscle cells allow muscle to contract. A human body contains trillions of cells.

Cerebral atrophy Abnormal condition in which the cerebrum (part of brain used for thought, communication, sensing, and voluntary movement) is abnormally small and intellectual impairment usually is present. Seen in CS, TTD, and some cases of XP.

Chromosome Single or paired DNA molecules in a cell. Humans have 46 chromosomes per cell nucleus.

Cleaver, Prof. James Laboratory of Radiobiology and Environmental Health, University of California, San Francisco,San Francisco CA 94143-0750; phone 415 476-4564, fax 415 476-0721. DNA repair researcher who discovered the biochemical defect in XP and introduced the UDS assay as the biochemical test for XP patients.

Cluster dish Cell culture vessel containing multiple identical cylindrical wells.

Cockayne's syndrome Rare genetic disease. A person has CS if there is both dwarfism and developmental delay, in addition to three of (1) abnormal sun sensitivity; (2) nerve deafness; (3) cataracts or pigmentary retinopathy; (4) characteristic facies (prominent ears, small chin, pointed nose, sunken eyes, and aged appearance with loss of adipose ("fatty") tissue); and (5) severe tooth decay. A patient may be diagnosed at birth, or may develop enough of these problems to be diagnosed later in childhood. Other problems seen in CS patients include microcephaly, cerebral atrophy, cerebral calcification, hydrocephalus, premature aging with short life expectancy, poor feeding, and predisposition to developing severe pneumonia.

Control cells Reference cells of known types that are used in laboratory experiments to compare with patients' cells e.g., UDS experiments will have both normal and XP cells in order to see if a suspected XP patient's cells are behaving like the normal cells or the XP cells.

Coverslip Small, thin, rectangular sheet of glass used as a protective cover for a specimen on a glass microscope slide.

CS Abbreviation for Cockayne's syndrome.

Culture Laboratory container having live cells and cell culture medium.

Cytoplasm The part of the cell that is not the nucleus; the peripheral, generally largest part of the cell in which most of the cell's activities other than those involving synthesis of DNA and RNA take place.

dehydrate To remove water from e.g., use of solvents to dehydrate glass microscope slides as an important part of the slide staining process.

Deoxyribonucleic acid The "double helix" molecule that contains the cell's genes.

Developmental delay Failure of a child to normally follow milestones in mental developmental e.g., in learning to walk.

DNA Abbreviation for deoxyribonucleic acid.

DNA repair Process in which DNA that is damaged by UV or other injurious agents is regenerated by the body to remove the damage.

Dwarfism Condition in which a person is extremely short.

Emulsion, photographic Silver containing gelatin that is used to produce silver grains when the emulsion is exposed to light and then processed with photographic chemicals.

Emulsion, radioactive Special photographic emulsion that efficiently produces silver grain following exposure to radiation such as beta particles from tritium; used in autoradiography.

Enzyme Protein that is used by the body to convert a particular chemical into another chemical e.g., DNA repair enzymes convert damaged DNA into undamaged DNA.

Facies Facial appearance.

Feeding pump Mechanical device for introducing liquid nutrients into the stomach of a person who eats poorly. Sometimes used to prevent starvation in CS children who do not eat adequately.

Fibroblast Cell found in the skin and elsewhere, which has secretions that give skin its toughness and elasticity.

Gene A segment of DNA that provides the information on how the cell can carry out a specific function e.g., provides the"blueprint" for making an enzyme.

Gene therapy Experimental, futuristic technology for introducing the normal version of a gene into a person who is ill due to the absence of the normal form of a gene. In theory, gene therapy could be used some day to make the skin surface of XP patients resistant to sunlight, although this is unlikely to be possible for several years. Potential problems include difficulty of treating most types of cells in the body (e.g., eye and brain cells), possibility of the treatment not working indefinitely, and possible side effects such as allergic reactions or cancers.

Grain, silver Particle of silver metal about 1/10,000 inch in size, produced when photographic emulsion is exposed to light or radiation. The number of grains is proportional to the amount of light or radiation received by the emulsion.

Histogram Graph in which data are presented as a series of bars alongside each other.

Hoeijmakers, Prof. Jan H. Dept. of Cell Biology and Genetics, Erasmus University, 3000DR Rotterdam, The Netherlands (Holland); 001 31 10 4087199 phone, 4360225 fax. Dutch DNA repair researcher who worked on the first cloning of a human DNA repair gene, and who manages the Erasmus University, Rotterdam DNA repair research lab. Members of his laboratory invented the complementation testing method for identifying which genes are affected in XP and CS patients, cloned a CS gene and an XP gene, and prepared genetically engineered mice similar to XP patients that represent laboratory models for studying XP.

Hydrocephalus "Water on the brain." Abnormal condition in which the skull contains less brain tissue than normal, with extra cerebrospinal fluid (watery solution normally bathing the brain and spinal cord).

Incubator Boxlike laboratory machine for maintaining cultures of cells at a constant temperature so that they will grow.

Irradiator Device for producing a particular type of radiation e.g., UV light.

Kaposi, Moritz Hungarian dermatologist who discovered XP.

Keating, Mr. Jay Computer programmer and video specialist with Picture This! who did video and software work for this CD ROM.

Kleijer, Dr. W.J Erasmus University, P.O. Box 1738, 3000DR Rotterdam, The Netherlands,011 31 10 4087223 phone, 4087200 fax. Dutch laboratorian performing prenatal diagnosis of CS and XP. Dr. Kleijer also performs diagnosis of ataxia telangiectasia.

Kraemer, Dr. Kenneth National Cancer Institute, Bldg 37 Room 3E24, National Institutes of Health, Bethesda MD 20892; (301) 496-9033 phone, 496-8419 fax. A dermatologist and XP researcher who participated in the early studies identifying the genes affected in XP. He has a registry of XP patients, has written an educational pamphlet on "Understanding Xeroderma Pigmentosum", and is always happy to hear of new XP and CS patients and to offer them and their physicians advice. He may also be able to provide information on experimental therapy with Acutane.

Mahar Name of family affected by XP. The parents, Dan and Caren, are President and Vice President of XPS, Inc. Their younger daughter, Katie, is a well known XP patient.

Medium, Cell culture Liquid preparation typically containing salts, vitamins, amino acids, sugar, antibiotics, acidity indicator, and cattle blood serum that is used to feed human cells grown in laboratory cultures.

Melanoma,malignant A skin cancer arising from the cells that produce the pigment that gives skin its color. Melanomas are extremely dangerous because they can easily spread to other parts of the body and are very difficult to stop once they spread; but they are less common than basal and squamous cell carcinomas of the skin.

Microcephaly Condition in which the head is abnormally small, generally with associated intellectual impairment.

Microscope Instrument for examining cells under high magnification, using glass microscope slides.

Mitosis The process in which one cell divides to form two cells.

Mutation Process in which DNA's structure is permanently altered. This may have serious consequences, such as inability to make a normal enzyme for DNA repair with resulting abnormal sensitivity to UV light (as occurs in CS and XP).

Neurological degeneration Deterioration of part of the nervous system e.g., the brain; seen in CS and XP.

Nucleotide Basic building block of DNA and RNA.

Nucleotide excision repair Process in which an area of DNA damaged by UV is cut out and replaced with DNA identical to the original, undamaged DNA.

Nucleus The central area of the cell that contains most of its DNA.

Oligonucleotide Several nucleotides linked together, essentially a very small DNA or RNA molecule. An example is the approximately 30 nucleotide fragment removed from UV damaged DNA in nucelotide exicisuon repair.

Permount Commercial transparent glue that is used to secure a cover slip to a glass microscope slide.

PIBIDS Acronym for several abnormal features seen in trichothiodystrophy patients: Photosensitivity, Ichthiosis (dry,scaly skin), sulfur-deficient Brittle hair, Intellectual impairment, Decreased fertility, and Short stature. Use of this term is controversial because not all TTD patients have all of these conditions.

Phosphate buffered saline Salty buffer that is used to briefly replace cell culture medium when cultured cells are experimentally exposed to UV, since cell culture medium in contrast to the saline blocks UV light and would interfere with the experiment.

Photochemical change Chemical change in a molecule induced by exposure to light e.g., DNA damage induced by UV.

Prenatal diagnosis Laboratory procedure in which cells taken from a pregnant woman are used to see if the fetus has an abnormal condition such as CS or XP. Prenatal diagnosis for CS and XP is not available in the US but is provided by laboratories in Europe. Hair Research Center, University of California San Francisco, 350 Parnassus Ave., Suite 505, San Francisco CA 94117; (415) 476-3636 phone, fax 476-3686. Performs hair amino acid analysis to assist in diagnosis of suspected TTD patients, and provides clinical advice for cases of TTD.

Protein Large molecule produced by the cell using the information contained in a gene.

Radiation Form of energy or energetic particles capable of causing changes in a molecule e.g, ionizing (creating charged particles) radiation such as X-and gamma rays, and nonionizing radiation such as UV.

Radioactive Material that is unstable, breaking down to form another material and also radiation. Tritium is an example.

Retinopathy, pigmentary Abnormal condition in which the light detecting retina of the eye deteriorates.

Ribonucleic acid Chemical similar to DNA, made in the nucleus using information contained in genes. An important form of RNA, messenger RNA, represents a copy of a gene that has the same information as the gene, and is used to tell the cell how to make a protein.

RNA Abbreviation for ribonucleic acid.

RNA polymerase Enzyme used to make RNA using genes as the blueprint.

RNA synthesis inhibition by UV Assay for identifying the biochemical abnormality in CS patients. The test measures how much cellular RNA synthesis is inhibited by UV, with greater inhibition occurring in CS patients, many XP patients, and even rarer patients who have both CS and XP. The test measures cellular uptake of tritiated uridine as a measure of the level of RNA synthesis. The test has two versions: the grain counting method with autoradiography and glass microscope slides discussed in this CD ROM, which is very similar to the UDS assay for XP; and the liquid scintillation counter method in which a vial containing extracts of cells is scanned by a radiation detection instrument.

RNA transcription The process in which RNA is made using DNA.

S phase The portion of the cell's life during which it makes an extra copy of its DNA within the nucleus in preparation for dividing and becoming two cells. This provides both of the two cells with the complete collection of cellular DNA that they need to survive.

Share and Care Share and Care Cockayne's Syndrome Network, Inc. P.O. Box 552, Stanleytown VA 24168; (540) 629-2369 phone, 647-3739 fax. An educational, advocacy and support organization for helping CS patients and their families.

Slide, glassmicroscope Flat, small, rectangular sheet of glass on which is deposited a specimen for examination under a microscope e.g., skin fibroblasts processed in the UDS assay.

Slide, tissueculturechamber Special glass microscope slide on which there is an overlying plastic box whose base is the slide, and which contains cultured cells. The box may be removed after the culture is complete, leaving a slide with cells on it that can be reviewed under the microscope.

Solar keratosis Sunlight (UV) induced abnormal condition of the skin in which an area of skin becomes red and roughened; may lead to squamous cell carcinoma.

Stain Solution used to give color to one or more parts of the cell, allowing the cell to be seen easily under the microscope. An example is the nuclear fast red stain used in the UDS assay to stain the nuclei pink so that nuclei can be readily identified.

Thymidine Building block of DNA. The more DNA is made, the more thymidine is consumed by the cell to make the DNA. Laboratorians use tritiated thymidine to measure how much DNA synthesis is occurring; the more radioactive the DNA, the more tritiated thymidine is being consumed and the more DNA is being made.

Trichothiodystrophy Rare genetic disease in which there is brittleness of hair and low hair sulfur content. Some TTD patients are light sensitive due to a defect in a gene that also can cause XP when present in a different abnormal form.

Tritiated Containing tritium.

Tritium Radioactive hydrogen, which decays to produce nonradioactive helium plus beta radiation capable of producing silver grains in a radioactive emulsion.

Trypsin Digestive enzyme used in cell culture laboratories to dissolve the natural "glue" that fibroblasts and other cells secrete that causes the cells to stick to culture vessels. This "trypsinizing" of the cultured cells causes the cells to detach from the culture vessel so that they can be transferred to another container.

TTD Abbreviation for trichothiodystrophy.

UDS Abbreviation for unscheduled DNA synthesis.

Uridine Basic building block for RNA. The more RNA is made, the more uridine is consumed by the cell to make the RNA. Laboratorians use tritiated uridine to measure how much RNA synthesis is occurring; the more radioactive the RNA, the more tritiated uridine is being consumed and the more RNA is being made.

Ultraviolet light Invisible light that contains more energy per unit of light than visible light. Ultraviolet light can cause mutation and cell death by damaging DNA.

Unscheduled DNA synthesis Process in which DNA is made outside of the S phase. This is studied in the UDS autoradiography assay, as described in this CD ROM. In this assay, the ability of cells to repair UV damaged DNA in nucleotide excision repair is measured. The more repair occurs, the more tritiated thymidine is incorporated into the nucleus, and thus the more grains are produced in a photographic emulsion during subsequent autoradiography, so that the level of production of silver grains over the nucleus is a measure of the cell's ability to repair the UV damage. UDS is subnormal in XP, in concurrent CS and XP, and in some cases of TTD.

UV Abbreviation for ultraviolet light.

Virtual Reality Computer technology in which effects such as video and sound are used to create an impression that the material being reviewed is physically present.

Xeroderma pigmentosum Rare genetic disease in which nucleotide excision repair is defective and the cell thus is deficient in repairing DNA damaged by UV. Problems found in XP patients include sun sensitivity, freckling, and cancers of sun exposed areas of the skin, eyes, ears, mouth, and nose. In addition, some XP patients develop neurological problems such as intellectual impairment, deafness, speech problems, and difficulty walking.

XP Abbreviation for xeroderma pigmentosum.

XP variant Patient with relatively mild XP symptoms, but with normal results in the UDS assay. These patients are deficient in another process the cell has for handling DNA damage, postreplication recovery.

XPS, Inc. 57 Sleight-Plass Rd., Poughkeepsie NY 12603; phone and fax (914) 473-4735. An educational, advocacy and support organization for helping XP patients and their families.

Yarosh, Dr. Daniel President of Applied Genetics, Inc.

Zwitterion Molecule with both positive and negative electrical charge, like the amino acids that are the building blocks of proteins.