Clinical pharmacokinetics of a placenta-derived factor XIII concentrate in type I and type II factor XIII deficiency

Factor XIII deficiency has been classified into two categories: type I deficiency, characterized by the lack of both the a and b subunits; and type II deficiency, characterized by the lack of the a subunit alone. To clarify the genetic bases of these diseases, previously reported cases of the type I deficiency were examined at the DNA level. DNA sequence analysis showed that a nucleotide triplet (AAC) was inserted within the codon for Tyr-80 in exon III of the gene for a female proband's b subunit, resulting in the creation of a stop codon. Restriction digestion of amplified DNAs confirmed that the proband and her sister were homozygotes, and their family members were heterozygotes of this mutant allele. A truncated protein composed of 79 amino acids could be synthesized by these homozygotes; however, such a protein would not be secreted or it would degrade quickly, because there were normal amounts of the mutant mRNA, but no b subunit was detected in these patients. The a subunit deficiency of these patients must be a secondary to the b subunit deficiency, as their gene for the a subunit was intact, and the a subunit in their platelets was present within normal levels.

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Factor XIII deficiency type I

Blood Coagulation & Fibrinolysis ◽

10.1097/00001721-199212000-00032 ◽

1992 ◽

Vol 3 (6) ◽

pp. 810

Author(s):

F. Rodeghiero ◽

A. Tosetto ◽

G. Castaman ◽

M. Ruggert

Keyword(s):

Factor Xiii ◽

Type I ◽

Factor Xiii Deficiency ◽

Deficiency Type

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Molecular Mechanisms of Type II Factor XIII Deficiency: Novel Gly562-Arg Mutation and C-Terminal Truncation of the A Subunit Cause Factor XIII Deficiency as Characterized in a Mammalian Expression System

Blood ◽

10.1182/blood.v91.8.2830.2830_2830_2838 ◽

1998 ◽

Vol 91 (8) ◽

pp. 2830-2838 ◽

Cited By ~ 26

Author(s):

Nobumasa Takahashi ◽

Hiroaki Tsukamoto ◽

Hideaki Umeyama ◽

Giancarlo Castaman ◽

Francesco Rodeghiero ◽

...

Keyword(s):

Mammalian Cells ◽

Factor Xiii ◽

Molecular Mechanisms ◽

Expression System ◽

Nucleotide Sequence Analysis ◽

Type Ii ◽

Factor Xiii Deficiency ◽

Mammalian Expression ◽

Mammalian Expression System ◽

A Subunit

To explore the biological and clinical implications of the structure/function relationships in factor XIII, mutations in two patients with type II deficiency were identified and characterized in a mammalian expression system. Nucleotide sequence analysis of the A subunit gene showed that case no. 1 had a deletion of 4 bp (AATT) in exon XI and that, in case no. 2, Gly562 (GGG) had been replaced by Arg(AGG). The deletion in case no. 1 leads to a premature termination at codon 464. Restriction digestion of amplified DNAs confirmed that both cases were homozygous for their respective mutations. Reverse transcription-polymerase chain reaction analysis demonstrated that the level of mRNA was greatly reduced in case no. 1, whereas the level of mutant mRNA expressed in case no. 2 was normal. Molecular modeling calculated that Arg562 changed the conformation of the A subunit, suggesting misfolding and/or destabilization of the molecule. To determine how these mutations impaired synthesis of the A subunit, recombinant A subunits bearing the mutations were expressed in mammalian cells. Pulse-chase experiments showed that the mutants were synthesized normally but disappeared rapidly, whereas the wild-type remained. These results indicate that both mutant proteins with an altered conformation become prone to rapid degradation, resulting in factor XIII deficiency in these patients.

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Heat-Etching with a Bullivant Type II Simple Freeze-Cleave Device

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100067522 ◽

1970 ◽

Vol 28 ◽

pp. 106-107 ◽

Cited By ~ 1

Author(s):

Ronald S. Weinstein ◽

N. Scott McNutt

Keyword(s):

New Zealand ◽

General Hospital ◽

Massachusetts General Hospital ◽

Type I ◽

Type Ii ◽

Collaborative Effort ◽

Temperature And Pressure ◽

The University

The Type I simple cold block device was described by Bullivant and Ames in 1966 and represented the product of the first successful effort to simplify the equipment required to do sophisticated freeze-cleave techniques. Bullivant, Weinstein and Someda described the Type II device which is a modification of the Type I device and was developed as a collaborative effort at the Massachusetts General Hospital and the University of Auckland, New Zealand. The modifications reduced specimen contamination and provided controlled specimen warming for heat-etching of fracture faces. We have now tested the Mass. General Hospital version of the Type II device (called the “Type II-MGH device”) on a wide variety of biological specimens and have established temperature and pressure curves for routine heat-etching with the device.

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Labelling of non-A, non-B hepatitis infected chimpanzee hepatocytes with nuclease-gold conjugates

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100111367 ◽

1984 ◽

Vol 42 ◽

pp. 250-251

Author(s):

G. D. Gagne ◽

M. F. Miller ◽

D. A. Peterson

Keyword(s):

Endoplasmic Reticulum ◽

Experimental Infection ◽

Uranyl Acetate ◽

Type I ◽

Cellular Injury ◽

Type Ii ◽

Tubular Structures ◽

Type Iii ◽

Type Iv ◽

Infected Chimpanzee

Experimental infection of chimpanzees with non-A, non-B hepatitis (NANB) or with delta agent hepatitis results in the appearance of characteristic cytoplasmic alterations in the hepatocytes. These alterations include spongelike inclusions (Type I), attached convoluted membranes (Type II), tubular structures (Type III), and microtubular aggregates (Type IV) (Fig. 1). Type I, II and III structures are, by association, believed to be derived from endoplasmic reticulum and may be morphogenetically related. Type IV structures are generally observed free in the cytoplasm but sometimes in the vicinity of type III structures. It is not known whether these structures are somehow involved in the replication and/or assembly of the putative NANB virus or whether they are simply nonspecific responses to cellular injury. When treated with uranyl acetate, type I, II and III structures stain intensely as if they might contain nucleic acids. If these structures do correspond to intermediates in the replication of a virus, one might expect them to contain DNA or RNA and the present study was undertaken to explore this possibility.

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Comparative surface and ultrastructural views of methylotrophic bacteria by TEM, STEM, SE, and freeze-etch electron microscopy.

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100128274 ◽

1987 ◽

Vol 45 ◽

pp. 792-793

Author(s):

T.A. Fassel ◽

M.J. Schaller ◽

M.E. Lidstrom ◽

C.C. Remsen

Keyword(s):

Cytoplasmic Membrane ◽

Structural Features ◽

Methylotrophic Bacteria ◽

Type I ◽

Type Ii ◽

Membrane Complex ◽

Oxidation Of Methane ◽

Methane Oxidizing Bacteria ◽

Wall Structures ◽

Methylomonas Albus

Methylotrophic bacteria play an Important role in the environment in the oxidation of methane and methanol. Extensive intracytoplasmic membranes (ICM) have been associated with the oxidation processes in methylotrophs and chemolithotrophic bacteria. Classification on the basis of ICM arrangement distinguishes 2 types of methylotrophs. Bundles or vesicular stacks of ICM located away from the cytoplasmic membrane and extending into the cytoplasm are present in Type I methylotrophs. In Type II methylotrophs, the ICM form pairs of peripheral membranes located parallel to the cytoplasmic membrane. Complex cell wall structures of tightly packed cup-shaped subunits have been described in strains of marine and freshwater phototrophic sulfur bacteria and several strains of methane oxidizing bacteria. We examined the ultrastructure of the methylotrophs with particular view of the ICM and surface structural features, between representatives of the Type I Methylomonas albus (BG8), and Type II Methylosinus trichosporium (OB-36).

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