Free ebook: Machiavelli's Laboratory
"Ethics taught by an unethical scientist"
100 BIOMEDICAL FACTOIDS
This page contains 100 factoids from the field of
biomedicine. There are about 180 additional pages in this
series.
This page has no value as a treatment guide or as a diagnostic
guide. It is merely a collection of interesting pieces of
information collected over the years. It has no connection with
any of the books published by the author and linked from this site.
This page is provided "as is", without warranty of any kind,
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© 2007 Jules J. Berman
17701
MORPHOLOGIC DIFFERENTIAL OF MAST CELL DISEASE INVOLVING BONE MARROW
Hodgkin's disease
non-Hodgkin's lymphoma
hairy cell leukemia
key words: morphology, JB
17702
SYSTEMIC MAST CELL DISEASE OCCURRING WITH OTHER MALIGNANCIES
Occurrence of a second malignancy is not rare
Usually a leukemia (acute myeloid or monocytic leukemia)
or lymphoma
key words: multiple primary, JB
17703
INFECTION-ASSOCIATED HEMOPHAGOCYTIC SYNDROME = IAHS
Includes but is not limited to all cases of viral associated
hemophagocytic syndrome = VAHS
May be related to the inherited disease familial erythrophagocytic
lymphohistiocytosis = FEL
Mortality 30% to 40% in acute phase
Must be distinguished from malignant histiocytosis
key words: virus, JB
17704
MALIGNANT HISTIOCYTOSIS
Rare
Most lesions previously diagnosed as MH are now presumed to be
reactive hemophagocytic syndromes or anaplastic large cell
lymphomas.
key words: lymphoma, terminology, JB
17705
DIFFERENTIAL DIAGNOSIS OF MALIGNANT HISTIOCYTOSIS
anaplastic large cell lymphomas
monoblastic leukemia (M5A)
reactive hemophagocytic syndromes
key words: lymphoma, JB
17706
PROSTATE CARCINOMA METASTATIC TO BONE MARROW
13% to 20% of prostate cancer patients have bone marrow involvement
This accounts for about a third of all bone marrow metastases in men
key words: metastasis, JB
17707
BONE MARROW METASTASES FROM CARCINOMA IN CHILDREN
In children neuroblastoma is the most common solid tissue tumor
Neuroblastoma has the highest frequency of bone marrow involvement
(over 50%)
Other childhood tumors that metastasize to bone
Ewing sarcoma
Fibrosarcoma
Ganglioneuroblastoma
Medulloblastoma
Medulloblastoma
Osteosarcoma
Retinoblastoma
Rhabdomyosarcoma
Childhood tumors that rarely mestastasize to bone:
Central nervous system tumors other than medulloblastoma
Hepatoblastomas
Nephroblastomas
key words: metastasis, pediatric, JB
17708
SIZE OF CELLS IN CARCINOMA METASTATIC TO BONE MARROW
With few exceptions, carcinomas cells that have metastasized to
bone marrow are larger than any normal bone marrow cells (except
mature megakaryocytes).
key words: morphology, JB
17709
SMALL ROUND CELL TUMORS IN MARROW IN CHILDREN
Ewing sarcoma
leukemia
lymphoblastic lymphoma
medulloblastoma
neuroblastoma
retinoblastoma
rhabdomyosarcoma
key words: childhood, pediatric, JB
17710
ZENKER FIXATION
Zenker fixation is commonly employed for bone marrow specimens
L26 (CD20), a B-cell marker, does not react in
Zenker-fixed tissue.
key words: fixative, histology, immunostain, JB
17711
Simon M,Pedeutour F, Sirvent N, Grosgeorge J, Minoletti F, Coindre J
Jos M, Lacombe T, Mandahl N, Craver RD, Blin N, Sozzi G, Turc-Carel C,
O'Brien KP, Kedra D, Fransson I, Guilbaud C, Dumanski JP.
Deregulation of the platelet-derived growth factor B-chain
gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma
protuberans and giant-cell fibroblastoma.
Nature genetics or J clin inv 1996 or 1997.
key words: carcinogenesis, oncogene, JB
17712
INCIDENCE OF GASTRIC LYMPHOMA.
Primary lymphoma accounts for about 5% of gastric cancer.
According to SEER statistics, the incidence of gastric lymphoma
in patients over 60 years of age has doubled between 1973 and 1986.
key words: epidemiology, JB
17713
GASTRIC CANCER VERSUS GASTRIC DYSPLASIA.
In general, gastric histologic lesions that would have been called
dysplasia in the U.S. were classified as carcinoma in Japan.
--------------------
Schlemper RJ, Itabashi M, Kato Y, Lewin KJ, Riddell RH, Shimoda T,
Sipponen P, Stolte M, Watanabe H, Takahashi H, Fujita R.
Differences in diagnostic criteria for gastric carcinoma
between Japanese and Western pathologists.
Lancet 349:1725-1729, 1997.
key words: stomach, preneoplasia, morphology, JB
17714
OVERCALLING ASCUS.
There is a perception that overcautious pathologists diagnose
ASCUS when the smear is not entirely normal, in order to be
sure no lesions are missed.
The "normal" rate of ASCUS is about 5%.
--------------------
Gilbert S. Pap Smears, once a reassuring routine now create anxiety.
New York Times, Sunday, June 22, 1997
key words: pap smear, preneoplasia, cervix, JB
17715
FREELANCE AUTOPSIES.
Vidal Herrera runs a free-lance autopsy service,
Autopsy/Post Services Inc., founded 1989.
Their motto:
"We give the dead a voice."
They expect to do about 1,000 autopsies in 1989
at $2,000 to $3,000 per autopsy.
key words: postmortem, JB
17716
INCIDENT OF SCIENTIFIC MISCONDUCT IN BRITAIN.
A senior consultant physician (John Anderton) was fired for
conducting a 15 month sham drug trial.
Apparently, Dr. Anderton suffered a breakdown after losing a fight
to save a renal transplant unit.
An acquaintance opined that Dr. Anderton was downhearted and
felt, "What the hell, nothing matters anymore."
--------------------
Dyer C. Consultant struck off over research fraud.
BMJ 315:205 (inclusive) 1997
key words: faking data, ethics, fradulent research, JB
17717
MEDLINE SEARCHES.
Over 10 million medical articles are in existence.
A third of these are indexed in Medline.
Entry of articles onto Medline is open to human error that occurs
when key words are assigned to an article and due to typographic
errors that occur when the abstract is re-typed.
Some sections of indexed journals are not entered into Medline
(e.g. the News section of BMJ).
It has been estimated that about 40% of information
that should be included in Medline is missed,
and can only be found in the paper journal.
--------------------
Greenhalgh T. How to read a paper: the Medline database.
BMJ 315:180-183, 1997
key words: medlars, database, public domain, library, JB
17718
HEALTH INSURANCE PORTABILITY AND ACCOUNTABILITY ACT OF 1996
= HIPAA, Pub L No. 104-191, :261, 262
Sets timetables for establishing federal policy on security
and privacy of electronic health data and standards for
electronic health data transactions.
If congress fails to enact such legislation, the secreatry
of health and human services will write rules that will
become law.
HIPAA gives the USDHHS 18 months to establish a number of
electronic information protocols including unique identifiers
for patients.
key words: law, legal, medicolegal, confidentiality, JB
17719
DERMATOFIBROSCARCOMA PROTUBERANS (HISTOLOGIC DIFFERENTIAL DIAGNOSIS)
dermatofibroma
diffuse neurofibroma
fibrosarcoma
myxoid liposarcoma
malignant fibrous histiocytoma
key words: soft tissue, JB
17720
BEDNAR TUMOR (HISTOLOGIC DIFFERENTIAL DIAGNOSIS)
pigmented neurofibroma
cellular blue nevus
amelanotic spindle cell melanoma
pigmented malignant schwannoma
key words: skin, soft tissue, JB
17721
EXTRAMAMMARY PAGET'S DISEASE (HISTOLOGIC DIFFERENTIAL DIANGOSIS)
Bowen's disease
melanoma in situ
sebaceous carcinoma
trichilemmal carcinoma
epidermotropic metastatic adenocarcinoma
key words: skin, JB
17722
PAGETOID SQUAMOUS CARCINOMA IN SITU (HISTOLOGIC DIFFERENTIAL DIAGMNSIS)
Paget's disease
melanoma in situ
sebaceous carcinoma
malignant hidroacanthoma simplex
trichilemmal carcinoma
key words: skin, JB
17723
GLUCAGONOMA ASSOCIATED NECROLYTIC MIGRATORY ERYTHEMA.
Histologic differential diagnosis:
Necrolytic acral erythema.
Biotin deficiency.
Zinc deficiency.
Niacin deficiency.
Essential fatty acids deficiency.
key words: skin, JB
17724
GLUCAGONOMA ASSOCIATED NECROLYTIC MIGRATORY ERYTHEMA.
Look for migratory annular erythematous patches:
Superficial necrosis.
Vesicle formation.
key words: endocrine skin, JB
17725
LYMPHOEPITHELIOMA-LIKE CARCINOMA OF THE SKIN
Histologic differential diagnosis:
metastatic nasopharyngeal carcinoma
lymphoma cutis
Merkel cell tumor
cutaneous lymphadenoma
metastatic squamous cell carcinoma
key words: skin, JB
17726
MALAKOPLAKIA OF SKIN
Usually occurs as nodules or draining ulcers in the perianal or
inguinal region
Seen more often in immunocompromised persons
key words: malacoplakia, skin, JB
17727
MALAKOPLAKIA OF SKIN
Histologic differential diagnosis:
infectious granulomas
granular cell tumor
histiocytic syndromes
hemocytophagic syndromes
key words: malacoplakia, skin, JB
17728
DISSEMINATED ASPERGILLOSIS
Can produce a panniculitis
Histologic differential diagnosis:
mucormycosis
pseudoallescheria boydii
fusarium
inflammatory panniculitis
key words: fungus, skin, JB
17729
HYPOPIGMENTED VARIANT OF MYCOSIS FUNGOIDES
Histologic differential diagnosis:
Pityriasis lichenoides chronica
Superficial gyrate erythema
Subacute dermatitis
key words: tcell, skin, JB
17730
LICHEN MYXEDEMATOSUS = SCLEROMYXEDEMA
Histologic differential diagnosis:
pretibial myxedema
granuloma annulare
lupus erythematosus
reticular erythematous mucinosis
key words: skin, JB
17731
LICHEN MYXEDEMATOSUS = SCLEROMYXEDEMA
multiple small firm densely grouped papules
face, upper trunk, extensor forearms, hands
key words: skin, JB
17732
LICHEN MYXEDEMATOSUS = SCLEROMYXEDEMA
Histology:
increased dermal mucin
proliferating fibroblasts
increased collagen deposition
minimal to absent perivascular lymphocytic infiltrate
key words: skin, JB
17733
CUTANEOUS MERCURY GRANULOMA
The mercury appeasrs ad black globules of varying sizes in the
dermis and subcutaneous tissue, with areas of necrosis
Usually produced by body builders trying to artifacually
pump up their muscles by injecting a heavy metal
key words: skin, JB
17734
SPINDLE CELL LIPOMA
Histologic differential diagnosis:
diffuse neurofibroma
nodular fasciitis
liposarcoma
pleomorphic lipoma
key words: soft tissue, JB
17735
GIANT CELL FIBROBLASTOMA
mostly in male patients
usually younger than 10 years of age
Histologic differential diagnosis:
malignant fibrous histiocytoma
myxoid liiposarcoma
schwannoma
fibromatosis
key words: soft tissue, JB
17736
AGGRESSIVE DIGITAL PAPILLARY ADENOMA
Almost exclusively on fingers
male to female ration of 7:1
Histologic differential diagnosis:
eccrine poroma
cutaneous mixed tumor
tubular apocrine adenoma
metastatic adenocarcinoma
key words: skin, JB
17737
BACILLARY ANGIOMATOSIS
Seen mostly in AIDS patients
Seen mostly on face or on oral, nasal and conjunctival mucosa
Look for finely particulate basophilic materal
Material is mostly located in vessel walls and intercellular spaces
Warthin-Starry demonstrates that the blue clumps are
extracellular bacilli
key words: skin, JB
17738
BACILLARY ANGIOMATOSIS.
Histologic differential diagnosis:
Epithelioid (histiocytoid) hemangioma.
Pyogenic granuloma.
Kaposi's sarcoma.
Capillary hemangioma.
key words: skin, JB
17739
PORPHYRIA CUTANEA TARDA.
Histology:
Subepidermal bulla.
Scant inflammation.
Thickened dermal vessels.
Caterpillar bodies (in basement membrane).
key words: skin, JB
17740
ECCRINE POROCARCINOMA.
large (up to 5 cm) verrucous plaque on lower extremity (usually)
patients usually over 65 years old
key words: skin, JB
17741
CUTANEOUS MYIASIS
The female botfly (Dermatobia hominis) attaches her eggs
to a mosquito. When the mosquito fees on a human, the botfly
larvae enter the skin though the site of the mosquito's bite.
The warble forms just under the skin, where the larvae enter
and live for up to six months.
key words: skin, parasite, JB
17742
MICROCYSTIC ADNEXAL CARCINOMA
= syringomatous carcinoma
= sclerosing sweat duct carcinoma
The dermis and often the subcutis are infitrated by thin strands
of tumor.
Well differentiated variants may form cysts and tubules of
keratinocytes.
key words: skin, JB
17743
MICROCYSTIC ADNEXAL CARCINOMA (DIFFERENTIAL HISTOLOGIC DIAGNOSIS)
syringoma
morpheaform basal cell carcinoma
metastatic carcinoma
adenosquamous carcinoma
key words: skin, JB
17744
CUTANEOUS ADENOID CYSTIC CARCINOMA
Often > 5 cm diameter
key words: tumor size, skin, JB
17745
PSEUDOCYST OF THE AURICLE
Fluid-filled swelling of the external ear skin, due to an
intracartilagenous cavity, possibly related to chondritis
key words: skin, JB
17746
SUBCUT. TCELL LYMPHOMA WITH HEMOPHAGOCYTIC HISTIOCYTIC PANNICULITIS
The subcutaneous tissue is involved by a t-cell lymphoma
often associated with cytophagic histiocytic panniculitis
Can mimic panniculitis
Hemophagocytosis my be present in:
bone marrow
lymph nodes
liver
spleen
Most patients are between 19 and 54 years of age, with a mean
of 35 years.
key words: skin, JB
17747
PROLIFERATIVE FASCIITIS
Peak incidence 40-70 years
Most lesions occur in the extremities
Usually presents as a rapidly growing nodule that is 2-3 cm
in size
key words: skin, soft tissue, age, JB
17748
PROLIFERATIVE FASCIITIS (HISTOLOGIC DIFFERENTIAL DIAGNOSIS)
Nodular fasciitis
Ganglioneuroblastoma
Rhabdomyosarcoma
Large cell carcinoma
key words: skin, soft tissue, JB
17749
TARGETOID HEMOSIDEROTIC HEMANGIOMA
Presents as a small purple targetoid papule 2-3 mm
in diameter
Look for dilated vessels with intraluminal papillary
projections of endothelial cells
There is red cell extravasation, and thrmbi in late stages
key words: skin, soft tissue, JB
17750
TARGETOID HEMOSIDEROTIC HEMANGIOMA (DIFFERENTIAL DIAGNOSIS)
Patch stage Kaposi's sarcoma
progressive lymphangioma
lipodermatosclerosis
Acroangiodermatitis = acral capillary angiomatosis
key words: skin, soft tissue, JB
17751
AGGRESSIVE ANGIOMYXOMA = AAM
Locally infiltrative
Occurs chiefly in genital, perineum and pelvic areas
Most lesions occur in women 25-60 years of age
Tumors can range in size from several cm up to 20 cm
The tumors are grossly gelatinous
Looke for spindle and stellate cells in a loose myxoid stroma
Vessels are prominent
key words: skin, soft tissue, JB
17752
DIFFERENTIAL DIAGNOSIS OF AGGRESSIVE ANGIOMYXOMA (AAM)
Angiomyofibroblastoma
Botryoid rhabdomyosarcoma
Myxoid leiomyoma
Myxoid lipoma
Myxoid liposarcoma
Myxoid neurofibroma
Myxoma
Spindle cell lipoma
key words: skin, soft tissue, JB
17753
BRITAIN OUTLAWS USING CELL PHONES WHILE DRIVING
In Britain, you can't use a mobile phone while
you're driving.
They know that it causes accidents.
key words: law, legal, forensic, safety, JB
17754
DR GORGAS AND THE PANAMA CANAL
Dr. William C. Gorgas helped the construction of the Panama Canal
by destroying mosquito breeding grounds, thus bringing yellow fever
and malaria under control.
key words: history, public health, vector, epidemiology, JB
17755
TYPHOID MARY
Mary Mallon was a carrier of the typoid bacillus who worked as
a cook in New York City in the early 20th century. She is
reputed to be the cause of at least 3 deaths and 51 cases of
typoid fever.
key words: history, salmonella, vector, epidemic, JB
17756
TENNIS ELBOW
= epicondylitis
Can be caused by playing tennis or from carrying a heavy weight with
arms extended
key words: terminology, JB
17757
CHINESE RESTAURANT SYNDROME
Some people respond to Monosodium Glutamate (MSG), in Chinese
food, with flushing, headache, perioral numbness
MSG is seldom used anymore in the preparation of Chinese food.
key words: toxicology, epidemiology, JB
17758
PICA
Pica is a craving to eat something that is not food.
It is named after the magpie (pica pica) which has a reputation
for sticking its beak into all sorts of objects.
key words: toxicology, epidemiology, terminology, JB
17759
THE FIRST TEST TUBE BABY
Louise Brown, born July 25, 1978
key words: history, JB
17760
SAME THING DIFFERENT WORDS
SI = metric system = Systeme Internationale d'Unites
key words: terminology, JB
17761
KRILL
Krill refers to about 85 species of planktonic crustaceans that
are the diet of whales. Most are less than an inch in size and
look like tiny shrimp or lobsters.
key words: nutrition, whale, ocean, JB
17762
FAMILIAL LIVER ADENOMAS
The authors reported a family in which the mother and 3 of 5
children had hepatic adenomas
The mother's father and paternal grandfather had hepatocellular
carcinoma
--------------------
Foster JH, Donohue TA, Berman MM. Familial liver-cell
adenomas and diabetes mellitus. New Engl J Med 299:239-241, 1978
key words: inherited, predisposition, hcc, JB
17763
HEPATITIS B VIRUS INTEGRATION SITE-6
Integration of DNA from the hepatitis B virus
frequently occurs in human hepatocellular carcinomas.
Rearrangements of the DNA domain in the area of the integration
site (4q32.1) occurs in 10% of liver tumors regardless of whether
they were HBV-related or not.
--------------------
Pasquinelli C, Garreau F, Bougueleret L, Cariani E, Grzeschik KH,
Thiers V, Croissant O, Hadchouel M, Tiollais P, Brechot C.
Rearrangement of a common cellular DNA domain on
chromosome 4 in human primary liver tumors.
J Virol 62:629-632, 1988
key words: carcinogenesis, hcc, JB
17764
HEPATIC LEUKEMIA FACTOR.
A t(17;19) chromosomal translocation in early B-cell acute
leukemia resulted in chimeric transcripts
that contained sequences from the E2A basic helix-loop-helix
transcription factor gene on chromosome 19, fused to
sequences from the HLF gene on chromosome 17.
HLF closely related to the leucine zipper-containing transcription
factors DBP (albumin D box-binding protein) and to TEF
(thyrotroph embryonic factor).
--------------------
Inaba T, Roberts WM, Shapiro LH, Jolly KW, Raimondi SC, Smith SD,
Look AT. Fusion of the leucine zipper gene HLF to the E2A gene in
human acute B-lineage leukemia. Science 257:531-534, 1992
key words: leukemogenesis, carcinogenesis, JB
17765
ALPHA HEREGULIN
= NEU differentiation factor = ndf
The NEU/ERBB2 protooncogene codes for a molecule that is
closely related to epidermal growth factor receptor (EGFR)
Heregulin is a 44-kD glycoprotein that interacts with
the NEU/ERBB2 receptor tyrosine kinase to increase its
phosphorylation on tyrosine residues during mouse and
rat development (midgestation).
--------------------
Orr-Urtreger A, Trakhtenbrot L, Ben-Levy R, Wen D, Rechavi G,
Lonai P, Yarden Y. Neural expression and chromosomal
mapping of NEU differentiation factor to 8p12-p21.
Proc Natl Acad Sci 90:1867-1871, 1993
key words: egf, oncogene, JB
17766
NEU ONCOGENE
NEU is a dominant transforming gene in tumors of the
peripheral nervous system induced by transplacental
treatment of rat embryos with N-ethylnitrosourea.
The period of susceptibility of NEU to carcinogenesis
correlates with its expression during development
(midgestation)
key words: oncogene, JB
17767
HIPPOCALCIN
Hippocalcin is a 23-kD Ca(2+)-binding protein first identified in the
rat hippocampus
key words: biochemistry, JB
17768
HIRSCHSPRUNG DISEASE
= Aganglionic megacolon
Can result from mutations in any of several genes including
dominant mutations in the RET gene and a recessive mutation
in the endothelin receptor type B gene on 13q22
key words: pediatric, colon, rectum, JB
17769
HIRSCHSPRUNG DISEASE
= Aganglionic megacolon
Short-segment type accounts for 80% of cases of Hirschsprung disease
Long-segment type accounts for 20% of cases of Hirschsprung disease
key words: pediatric, colon, rectum, JB
17770
BEUKES FAMILIAL HIP DYSPLASIA
Probably a type of spondyloepiphyseal dysplasia
Autosomal dominant
--------------------
Beighton P, Cilliers HJ, Ramesar R. Autosomal dominant
(Beukes) premature degenerative osteoarthropathy of the hip joint
unlinked to COL2A1. Am J Med Genet 53:348-351, 1994
key words: terminology, JB
17771
HOLT ORAM SYNDROME
= heart hand syndrome
= atriodigital dysplasia
Thumb anomaly and atrial septal defect
key words: terminology, JB
17772
HOMEO BOX
The homeo box is a 180-bp DNA sequence conserved in Drosophila
homeotic genes which regulate early development.
They share structural features with genes encoding some DNA-binding
proteins.
The homeotic genes are expressed in a series of partially
overlapping domains that extend along the axis of the embryo.
Our understanding of the biologic role of these genes comes mainly
from analysis of homeotic mutants in Drosophila; these mutants
characteristically develop normal structures at abnormal locations
along the axis.
key words: transcription, development, homology, homolog, JB
17773
HOX GENE FAMILY
The mammalian HOX gene family contains 38 homeo box gene members
located in 4 independent complexes named HOXA, HOXB, HOXC, and HOXD
(AKA HOX1, HOX2, HOX3, and HOX4, respectively).
These 4 clusters of genes are located on chromosomes 7, 17, 12, and 2, |
respectively. These genes are expressed during embryonic
development, at which time they have a determinant role in the body
plan organization.
key words: transcription, homology, homolog, JB
17774
RETROVIRUS RELATED ENDOGENOUS SEQUENCES
The replication cycle of exogenous retroviruses such as HTLVs require
integration of proviral DNA into host cell DNA.
Endogenous retroviral sequences (ERS) are transmitted genetically
in a classic mendelian manner through the germline (proviral DNA)
key words: virus, JB
17775
HUMAN T-CELL LEUKEMIA VIRUS ENHANCER FACTOR
= HTLF
A region of the human T-cell leukemia virus long terminal repeat
located between -155 and -117 is important in the regulation of gene
expression by the ETS family of transcription factors
HTLF binds to this Tcell LTR and contains a domain with homology
to the 'fork head' DNA binding domain.
HTLF gene maps to 2p22-p16
HTLF gene is distinct from another 'fork head' domain DNA binding
protein, ILF (mapped to chromosome 17q25)
The ETS1 gene is located on 11q23
Translocations between 2p22-p16 and 11q23 have been found in leukemia.
--------------------
Li C, Lusis AJ, Sparkes R, Tran SM, Gaynor R.
Characterization and chromosomal mapping of the gene encoding the
cellular DNA binding protein HTLF. Genomics 13:658-664, 1992
key words: oncogene, homology, homolog, JB
17776
HUNTINGTON DISEASE = HUNTINGTON CHOREA
Huntington disease, an autosomal dominant disease, gives rise to
progressive, selective neural cell death associated with choreic
movements, rigidity, and dementia.
Age of onset is variable but mode is 30-40 years.
Death, on average, occurs 17 years after diagnosis
key words: inherited, neurology, JB
17777
HUNTINGTON DISEASE = HUNTINGTON CHOREA
30 to 70 per million in most Western countries
lower in blacks, Japanese, and Finns
Autosomal dominant inheritance
Associated with increases in the length of a CAG triplet repeat
present in a gene called 'huntingtin' located on chromosome 4p16.3
key words: transcription, development, homology, homolog, JB
17778
ARE POPULAR PATHOLOGY INSTRUCTORS BETTER TEACHERS?
Medical students belonging to groups with the higest rated
instructors performed no better than those with who had
instructors with poor ratings.
--------------------
Fenderson BA, Damjanov I, Robeson MR, Rubin E. Relationship
of students' perceptions of faculty to scholastic achievement:
are popular instructors better educators?
Human Pathol 28:522-525, 1997
key words: academic, teaching, JB
17779
WHY KNOCK-OUT MUTATIONS ARE ATTEMPTED
In general, mutations that cause a gain of function produce
disease even when they occur in only one of a gene's two alleles
(i.e. these mutations are dominant). Examples are oncogenes
that cause abnormal cell lproliferation.
In general, mutations that cause a loss of function are recessive.
An example is cystic fibrosis.
Integrating an oncogene that causes dominant disease, such as c-myc,
into the genome of a fertilized mouse oocyte without altering the
mouse's own genes creates a transgenic, cancer-prone
mouse that transmits this trait to its offspring with a dominant
pattern of inheritance.
To create an animal model of an autosomal recessive disease
both alleles of the normal gene must be inactivated.
The technique of gene "knockout" was developed for this purpose.
key words: transgenic, JB
17780
TRANSGENIC MICE
In the early 1980s, methods were developed to culture totipotential
cells from the inner cell mass of the blastocyst,
These embryonic stem cells can be genetically altered and
then microinjected into the cavity of an intact mouse blastocyst
They can, from the blastocyst stage, populate all the tissues
of the developing mouse, forming a chimeric animal
If the embryonic stem cells contribute to the germ cells (sperm or
oocyte) of the developing mouse embryo, their entire haploid genome
can be passed on to subsequent generations.
key words: knockout, JB
17781
KNOCKOUT METHOD USING GENE TARGETING
The specific gene of interest is replaced with one that is inactive
To increase the probability that such replacement will occur,
rather than nonspecific random integration of the DNA, both ends
of the replacement gene are flanked by long DNA sequences homologous
to the sequences flanking the target gene (so-called homologous
recombination).
Since the frequency of homologous recombination is low, there must
be a way of selecting the rare cells in which the target gene
has been replaced by the constructed gene. Homologous recombination
actually replaces the host gene with the altered gene (rather than just
inserting the altered gene into some randome location in the genome).
One method is to include
a gene that encodes viral thymidine kinase in the knockout vector,
but outside the area of the vector included between the flanking
homologous DNA. A neomycin resistance gene is included between
the flanking regions.
Thymidine kinase confers sensitivity to ganciclovir.
The genetically engineered DNA is introduced into embryonic stem
cells that are then incubated with tissue-culture medium containing
neomycin and ganciclovir.
Embryonic stem cells that have incorporated the new DNA by homologous
recombination resist neomycin (positive selection).
By contrast, cells that have nonspecifically taken up genetically
engineered DNA, including the viral thymidine kinase, are killed by
ganciclovir because of the gene for this kinase, which lies outside
the region of specific homologous recombination (negative selection).
Clones that survive positive and negative selection are injected
into blastocysts to initiate the creation of chimeric mice
Chimeras with germ cells derived from the altered embryonic stem cells
can transmit the altered genome to their offspring
key words: transgenic, JB
17782
ESSENTIAL GENES IDENTIFIED BY KNOCKOUT MOUSE EXPERIMENTS
SF-1 (gene encoding steroidogenic factor 1) is essential for adrenal
and gonadal organogenesis.
WT-1 (the Wilms' tumor locus), is essential for renal development
Myogenin gene is necessary for skeletal-muscle formation
Glucocorticoid receptor is necessary fetal development
The estrogen receptor is necessary for female sexual maturation
RAG-2 (recombination-activating gene 2) and GATA-1 (which recognizes
a GATA-nucleotide motif) are critical to the development of lymphocytes
and erythrocytes, respectively.
key words: transgenic, JB
17783
COMBINING KNOCKOUT GENE DEFICIENCIES
Genetic deficiencies can be combined simply by cross-breeding mice
with knockout of different genes.
key words: transgenic, JB
17784
KNOCKOUT MOUSE MODES FOR ULCERATIVE COLITIS
Mice with inactivation of the interleukin-2 gene results in
ulcerative colitis
key words: transgenic, JB
17785
DISORDERS UNDERSTOOD BY GENE STUDIES THAT BYPASSED PATHOGENESIS
The genes responsible for the following diseases were determined by
positional cloning of their defects, not through pathogenetic
studies.
Duchenne's muscular dystrophy
Cystic fibrosis
Huntington's disease
key words: transgenic, JB
17786
KNOCOUT MICE WITH HUNTINGTON'S DISEASE
Mice with homozygous knockout of the gene for Huntington's
disease die as embryos instead of undergoing the postnatal
degeneration of their brains.
The abnormal expansion of nucleotides in the gene of patients with
Huntington's disease causes a deleterious gain of function, rather
than a loss of function. If it caused a loss of function, persons
with the Huntington's gene would have died as embryos.
key words: transgenic, JB
17787
LIMITATIONS OF STUDIES USING KNOCKOUT MICE
If a gene is expressed in different tissues where it may have
different functions, its inactivation may have multiple consequences.
A gene mutation may cause embryonic death or death soon
after birth, giving important information about the gene's role in
development but preventing further study of its action.
Also, the functions of two genes may overlap, in which case a
mutation in only one gene may not reveal an abnormal
phenotype.
key words: transgenic, JB
17788
DEFINITIONS
Aggregation technique - the zona pellucida of embryos at the
8-cell stage of development are removed and different embryos are
pushed together to yield a single embryo (used as an alternative
to microinjection).
Agouti - phenotype of the mouse coat characterized by black
hairs with a subapical yellow band.
Alleles - alternative forms of a genetic locus
A single allele for each locus is inherited separately
from each parent
Allogeneic - the allelic variation observed among members of the
same species.
key words: gene, genetics, terminology, JB
17789
DEFINITIONS
Backcross - a crossing of a heterozygous organism and one of its
homozygous parents.
Base pair - two bases (adenine - thymine or guanine - cytosine)
held together by weak bonds. Two strands of DNA are held together
in the shape of a double helix by the bonds between base pairs.
Blastocoel - the fluid-filled cavity of the blastocyst.
Blastocyst - stage in early animal development characterized by the
formation of a multicellular spherical shell enclosing a fluid-filled
cavity (the blastocoel).
key words: gene, genetics, terminology, JB
17790
DEFINITIONS
Calcium phosphate precipitation - a method of gene transfer from
viral vector to host in which plasmid DNA is precipitated by
calcium in solution and taken up by host cells by phagocytosis.
Candidate gene approach - the testing of cloned genes that map
in the region of a mutant for involvement in the phenotype
associated with a mutation.
key words: gene, genetics, terminology, JB
17791
DEFINITIONS
cDNA (copy DNA) - DNA synthesized from an RNA template using
reverse transcriptase.
Chimera - an organism or recombinant DNA molecules created
by joining DNA fragments from two or more different organisms.
Clones - a group of cells derived from a single ancestor.
Cloning - the process of asexually producing a group of cells
(clones), all genetically identical, from a single ancestor.
key words: gene, genetics, terminology, JB
17792
DEFINITIONS.
Cloning DNA:
In recombinant DNA technology, the use of DNA manipulation procedures
to produce multiple copies of a single gene or segment of DNA
is referred to as cloning DNA.
Concatamer integration: occurs when the entire genome of the vector,
including the bacterial plasmid, is integrated into the host genome.
Congenic strain: a strain that differs from another in the region
of one genetic locus and that is produced by at least
ten successive backcrosses or intercrosses to the control strain.
key words: gene, genetics, terminology, JB
17793
DEFINITIONS
Constitutive ablation - expression of a targeted gene results
in cell death; this mechanism for ablation is not
dependent on a drug to induce ablation.
contig - a series of contiguous, cloned DNA fragments,
assembled by determination of the overlap regions among clones.
Three vectors are in current use: YAC, P1, and closmid (plasmid
with cos sites).
copy number - the number of copies of a transgene integrated
into the host genome.
cosmid - a plasmid with cos sites usually about 40kb.
key words: gene, genetics, terminology, JB
17794
CRYOPRESERVATION
the technique of freezing tissues or cells or
other biological materials at very low temperatures in which the
materials remain genetically stable and metabollically inert.
Cryopreservation may involve freezers (-80 degrees Centigrade), or preservation with dry ice (-79
degrees) or liquid nitrogen (-196 degrees).
key words: gene, genetics, terminology, JB
17795
DEFINITIONS
Deletion mutation - a mutation caused by the removal
of one or more nucleotides from a gene or chromosome.
Electroporation - The exposure of cells to rapid pulses
of high-voltage current which renders the plasma membrane
of the cells permeable and thus allowing transfection.
Enhancer - DNA sequences that positively influence the
expression of a gene and which may be some distance from that gene.
key words: gene, genetics, terminology, JB
17796
GENETIC TRAPS
Enhancer traps are constructs that carry a reporter gene with a
start of translation (ATG codon) under the control of a minimal
(weak) promoter.
Used to visualize transcriptional activation
patterns and to identify and isolate genes expressed in
spatially and temporally regulated patterns
during development.
Gene traps are vectors that carry the reporter gene
(with or without the start codon ATG) 3' to a
splice acceptor site
A splice acceptor site is used instead of a promoter.
It is used primarily in embryonic stem cells to screen for genes
expressed during mouse embryogenesis.
key words: gene, genetics, terminology, JB
17797
DEFINITIONS
Genome - all the genetic material in the chromosomes of a particular
organism; its size is generally given as its total number of base pairs.
Hit and run vector - modified insertion vectors which have a
mutation in the homologous sequences.
These vectors will form a variety of different integration
products upon targeting.
Homeobox - A short stretch of nucleotides whose base sequence is
virtually identical in all the genes that contain it.
It has been found in many organisms from fruit flies to human beings.
In the fruit fly, a homeobox appears to determine when particular
groups of genes are expressed during development.
key words: gene, genetics, terminology, JB
17798
INDUCIBLE ABLATION.
Expression of the targeted gene is not by itself harmful to the cell,
but is capable of remdering cells selectively sensitive
to the killing action of certain drugs,
that cannot be metabolized by normal cells.
key words: gene, genetics, terminology, JB
17799
DEFINITIONS.
Insertional mutation: a mutation caused by the insertion
of at least one extra nucleotide base in a DNA sequence.
Lipofection: the introduction of transgenes across cell membranes,
using liposome vesicles formed by phagocytosis.
Microinjection: a technique for introducing a solution
of DNA into a blastocyst using a fine microcapillary pipet.
Molecular farming: the development of transgenic animals
to produce biomedical proteins (i.e. tissue plasminogen activator,
factor IX, and human hemoglobin).
key words: gene, genetics, terminology, JB
17800
DEFINITIONS.
Pronucleus - either of the two haploid gamete nuclei just prior
to their fusion in the fertilized ovum.
Transgenic lines are often generated by microinjection of the
transgene into the pronuclear region of these haploid gametes.
Reporter gene - encodes for an easily detectable protein.
For example, lacZ, CAT (chloramphenicol acetyltransferase),
and the luciferase genes all encode for bacterial enzymes.
Synteny - genes on the same chromosome. Synteny conservation is
defined as the occurrence of two or more pairs of homologous
markers on the same chromosome in two or more species.
Linkage conservation is conservation of synteny and of gene order.
Transomic technology - the microinjection of chromosome fragments into the embryonic
nucleus (permits the transfer of intact gene clusters).
XID mouse - a lab mouse that has a Y-linked immune deficiency gene.
key words: gene, genetics, terminology, JB
Last modified: December 5, 2006