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Untitled - D Ank Unlimited

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Castleman’s disease 137 catalytic antibodies<br />

Release of cytochrome c from the mitochondria can trigger a series of<br />

events leading to the activation of effector caspases. For example, procaspase<br />

9 is activated when complexed with dATP, APAF-1, and extramitochondrial<br />

cytochrome c. Following activation, caspase 9 can inhibit<br />

apoptosis by cleaving additional caspases.<br />

Activation of procaspase 9 can occur upon formation of a complex with<br />

Apaf-1 and cytochrome c. Caspase 9 may then activate additional caspases<br />

through proteolytic cleavage (e.g. procaspases-3, -6, and -7).<br />

with the cytoplasmic death domains of the receptor. Caspase<br />

9 activates disassembly in response to agents or insults that<br />

trigger release of cytochrome c from the mitochondria and is<br />

activated when complexed with dATP, APAF-1, and extramitochondrial<br />

cytochrome c. Caspase 3 appears to amplify caspase<br />

8, and caspase 9 signals into a full-fledged commitment to<br />

disassembly. Both caspase 8 and caspase 9 can activate caspase<br />

3 by proteolytic cleavage, and caspase 3 may then cleave vital<br />

cellular proteins or activate additional caspase by proteolytic<br />

cleavage. Many other caspases have been described. Caspases<br />

proteolytically disassemble cells. They are present in healthy<br />

cells as inactive proforms. During apoptosis, most caspases<br />

are activated by proteolytic cleavage. Caspase 9, however, may<br />

be active without being proteolytically cleaved. Activation is<br />

through autoproteolysis or cleavage by other caspases. Cleavage<br />

of caspases generates a pro-domain fragment and subunits of<br />

approximately 20 and 10 kDa. Active caspases appear to be<br />

tetramers consisting of two identical 20-kDa subunits and two<br />

identical 10-kDa subunits. Detection of either the 20- or 10-kDa<br />

subunit by immunoblotting may imply activation of the caspase.<br />

Colorimetric and fluorometric assays using fluorogenic peptide<br />

substrates can be used to measure caspase activity in apoptotic<br />

cells. Caspases cleave substrate proteins at the carboxyl termini<br />

of specific aspartates. Tetrameric peptides with fluorometric or<br />

colorimetric groups at the carboxyl terminal have been used<br />

to determine the Km values of caspases. Although there is<br />

preference for peptides with certain amino acid (aa) sequences,<br />

the aa sequence may have some variance. Caspases also have<br />

overlapping preferences for the tetrameric aa sequence (i.e., the<br />

same substrates can be cleaved by multiple caspases although<br />

one caspase may have a lower Km). Peptides containing groups<br />

that form covalent bonds with the cysteine residing at the active<br />

site of the caspase are often used to inhibit caspase activities.<br />

Castleman’s disease<br />

Also called giant lymph node hyperplasia. A disease of<br />

unknown etiology that involves both lymph nodes and extra-<br />

nodal tissues. Two histopathologic subtypes have been<br />

described. The first, termed hyaline-vascular angiofollicular<br />

lymph node hyperplasia, accounts for 90% of the cases. It usually<br />

affects young men who present with an asymptomatic mass<br />

in the mediastinum. Histopathologically, it reveals numerous<br />

small, follicle-like structures, frequently with radially penetrating,<br />

thick-walled, hyalinized vessels, concentrically arranged<br />

small lymphocytes around the follicular structures, called<br />

“onion skinning,” and extensive proliferation of capillaries<br />

in the interfollicular areas. The second type of Castleman’s<br />

disease is plasma cell angiofollicular lymph node hyperplasia,<br />

which comprises 10% of the cases. It is either a localized mass<br />

or a multicentered systemic disorder. The mass may consist<br />

of multiple matted lymph nodes with histopathologic features<br />

that include large hyperplastic follicles with fewer permanent<br />

penetrating vessels than in the hyaline-vascular type, with<br />

pronounced interfollicular plasma cytosis and permanent<br />

vascularity. A multicentric type of the plasma cell variant<br />

of angiofollicular lymph node hyperplasia is more aggressive.<br />

Affected patients may have increased risk for developing<br />

Kaposi’s sarcoma or immunoblastic lymphoma. Clinical<br />

features of plasma cell angiofollicular hyperplasia include fever,<br />

polyclonal hypergammaglobulinanemia, elevated sedimentation<br />

rate, and anemia.<br />

cat scratch disease<br />

Regional lymphadenitis, common in children following<br />

a cat scratch. The condition is induced by a small Gramnegative<br />

bacillus. Erythematous papules may appear on<br />

the hands or forearms at the site of the injury. Patients<br />

may develop fever, malaise, swelling of the parotid gland,<br />

lymphadenopathy that is regional or generalized, maculopapular<br />

rash, anorexia, splenic enlargement, and encephalopathy.<br />

Hyperplasia of lymphoid tissues, formation of<br />

granulomas, and abscesses may occur. A positive skin test,<br />

together with history, establishes the diagnosis. Gentamycin<br />

and ciprofloxacin have been used in treatment.<br />

catalase<br />

An enzyme present in activated phagocytes that causes degradation<br />

of hydrogen peroxide and superoxide dismutase.<br />

catalytic antibodies<br />

Antibodies that are exclusively specific for a particular ligand<br />

and are also catalytic. Approximately 100 reactions have been<br />

catalyzed by antibodies. Among these are pericyclic processes,<br />

C

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