Publications by authors named "Meek K"

Rare Ig and TCR coding joints can be isolated from mice that have a targeted deletion in the gene encoding the 86-kDa subunit of the Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase (DNA-PK). However in the coding joints isolated from Ku86-/- animals, there is an extreme paucity of N regions (the random nucleotides added during V(D)J recombination by the enzyme TdT). This finding is consistent with a decreased frequency of coding joints containing N regions isolated from C.

View Article and Find Full Text PDF

Objective: To investigate the origin and distribution of granular deposits in the corneas of 3 patients with granular dystrophy, 1 of whom had previously received a lamellar keratoplasty in which the granular dystrophy had recurred.

Method: Corneal tissue from 2 patients with primary granular dystrophy (patients 1 and 2) and from a patient with recurrent granular dystrophy (patient 3) was examined. Corneal graft tissue was fixed in (1) 3% glutaraldehyde in sodium cacodylate buffer, (2) 2.

View Article and Find Full Text PDF

In aging and diabetes, glycation of collagen molecules leads to the formation of cross-links that could alter the surface charge on collagen fibrils, and hence affect the properties and correct functioning of a number of tissues. The electron-optical stain phosphotungstic acid (PTA) binds to positively charged amino acid side-chains and leads to the characteristic banding pattern of collagen seen in the electron microscope; any change in the charge on these side-chains brought about by glycation will affect the uptake of PTA. We found that, upon glycation, a decrease in stain uptake was observed at up to five regions along the collagen D-period; the greatest decrease in stain uptake was apparent at the c1 band.

View Article and Find Full Text PDF

V(D)J rearrangement is the molecular mechanism by which an almost limitless number of unique immune receptors is generated. V(D)J rearrangement involves two DNA breaks and religations resulting in two DNA joints; coding and signal joints. If V(D)J recombination is impaired (as in murine SCID (C.

View Article and Find Full Text PDF

The precise orientation of the collagen fibrils in human cornea and sclera and the method by which these two areas fuse together at the limbus have never been determined, despite the importance of this information. From a consideration of the mechanics of the system, fibril orientation in the tissue has the potential to affect the curvature of the cornea so, by inference, refractive problems such as astigmatism involving an incorrect curvature of the cornea may be related to fibril orientation. The high intensity and small beam size of a synchrotron x-ray source has enabled us to study fibril orientation in post-mortem human cornea and sclera.

View Article and Find Full Text PDF

Purpose: The aim of this study was to evaluate the ultrastructure of acute calcification observed in alkali-injured rabbit corneas treated with synthetic inhibitor of metalloproteinases (SIMP).

Methods: A 12-mm alkali burn was made on the right corneas of 16 rabbits. Eight eyes were treated with topical phosphate-buffered SIMP, and eight control eyes were given the buffer only.

View Article and Find Full Text PDF

Regulation of the IkappaB alpha and IkappaB beta proteins is critical for modulating NF-kappaB-directed gene expression. Both IkappaB alpha and IkappaB beta are substrates for cellular kinases that phosphorylate the amino and carboxy termini of these proteins and regulate their function. In this study, we utilized a biochemical fractionation scheme to purify a kinase activity which phosphorylates residues in the amino and carboxy termini of both IkappaB alpha and IkappaB beta.

View Article and Find Full Text PDF

Purpose: To quantify the orientation of the collagen fibrils in the human limbus and to compare it with the orientation in the cornea and the sclera.

Methods: Fibril orientation was measured from 100 synchrotron x-ray diffraction patterns collected at intervals along lines across the cornea, limbus, and sclera.

Results: A distinct circumcorneal annulus of collagen fibrils was revealed in the limbus.

View Article and Find Full Text PDF

The gene product of XRCC4 has been implicated in both V(D)J recombination and the more general process of double strand break repair (DSBR). To date its role in these processes is unknown. Here, we describe biochemical characteristics of the murine XRCC4 protein.

View Article and Find Full Text PDF

Objective: To determine whether a recently developed test would correctly identify horses heterozygous for the severe combined immunodeficiency (SCID) trait.

Design: Case series.

Animals: 17 healthy Arabian horses that had previously produced foals with SCID, 1 healthy Arabian foal whose dam and sire had produced foals with SCID, 4 foals with SCID, and 1 healthy non-Arabian foal.

View Article and Find Full Text PDF

One of the strategies that the immune system utilizes to generate Ab and TCR diversity is programmed imprecision of coding joint formation. This is accomplished by both nucleotide loss and random nucleotide addition (N segments) to the termini of immune receptor coding segments before resolution. Although it has been known for more than a decade that terminal deoxynucleotidyl transferase is the enzyme responsible for N segment addition, the enzymes responsible for nucleotide loss have not been identified.

View Article and Find Full Text PDF

Purpose: This case report describes the structural characterization of the corneal stroma from a patient with Morquio syndrome type A.

Methods: A left penetrating keratoplasty was performed, and the cornea was examined using transmission electron microscopy and synchrotron x-ray diffraction. The interfibrillar proteoglycans were visualized in the electron microscope by using cuprolinic blue.

View Article and Find Full Text PDF

The equine SCID defect is more severe than its murine counterpart in that SCID foals are incapable of forming either coding or signal joints, whereas SCID mice manifest normal signal joint formation. To determine the basis of this difference and whether DNA-dependent kinase, catalytic subunit (DNA-PK(CS)), is involved in signal joint formation, equine DNA-PK(CS) transcripts were cloned and sequenced from normal and SCID cell lines. In the mutant allele, a frame-shift mutation truncates the protein N terminal of the domain with homology to the phosphatidylinositol 3-kinase family resulting in complete absence of full length DNA-PK(CS) and accounting for the kinase-negative phenotype of these cells; the mutation in SCID mice allows for some DNA-PK(CS) expression.

View Article and Find Full Text PDF

Objective: To compare the efficacy of two- and three-drug regimens for treating Mycobacterium avium complex (MAC) bacteremia in patients with AIDS.

Design: Randomized open-label clinical trial.

Setting: Outpatient HIV specialty centers' clinics.

View Article and Find Full Text PDF

Ultrastructural data from x-ray diffraction studies of the cornea were used to estimate the refractive indices of the collagen fibrils and extrafibrillar material of human, ox, trout, and rabbit corneas. X-ray diffraction measurements of the size and spacing of the collagen fibrils and the separation between the constituent molecules of the fibrils were taken from a previous species study. The tissue volume fractions occupied by the stromal components were estimated and their refractive indices were calculated using the Gladstone-Dale law of mixtures.

View Article and Find Full Text PDF

V(D)J recombination is targeted by recombination signal sequences (RSS) located immediately adjacent to immune receptor gene segments. While the RSS flanking D(H) segments appear to be equivalent, they are not randomly utilized. During D(H) to J(H) rearrangement, the 3' D(H) RSS is virtually exclusively utilized, suggesting that the 3' D(H) RSS could simply be a better target for the recombinase.

View Article and Find Full Text PDF

Germline epsilon (I epsilon) transcription is requisite for IgE switch recombination. I epsilon transcription is markedly increased by ligation of CD40 and/or by IL-4 stimulation. By contrast, we found previously that stimulation through CD30 inhibits I epsilon transcription in EBV-transformed B cell lines.

View Article and Find Full Text PDF

The ageing of connective tissues involves modifications of collagen, which are currently generating much interest amongst protein researchers. Protein glycation, a non-enzymic reaction involving sugar, appears to play a role in the evolution of age-related physical changes and diabetic complications-retinopathy, neuropathy, renal failure and atherosclerosis. Our studies show that the glycation of human corneal and scleral collagen produces increases in the collagen intermolecular spacing-these increases are similar to those we previously reported on the ageing of collagen in these tissues.

View Article and Find Full Text PDF

Two epikeratoplasty lenticules (Epi-L) with keratoconus host corneas (Epi-H) were removed by penetrating keratoplasty because of poor visual acuity although they were clinically clear. Light microscopy showed that the keratocytes were underpopulated and unevenly distributed in Epi-L. Transmission electron microscopy showed that abnormal sized proteoglycans (PGs) were unevenly accumulated in the stromas of both Epi-L and Epi-H.

View Article and Find Full Text PDF

This case report describes a 14-year-old girl with Hurler syndrome, who had received a successful bone marrow-transplant at the age of two. Corneal clouding was present at the time of transplant and has only partially cleared. A right penetrating keratoplasty was performed and the corneal specimen was examined by light microscopy, transmission electron microscopy with Cuprolinic blue staining for proteoglycans, and low-angle X-ray diffraction.

View Article and Find Full Text PDF

V(D)J rearrangement is the molecular mechanism by which an almost infinite array of specific immune receptors are generated. Defects in this process result in profound immunodeficiency as is the case in the C.B-17 SCID mouse or in RAG-1 (recombination-activating gene 1) or RAG-2 deficient mice.

View Article and Find Full Text PDF

To assess the potential of CD40 ligand (CD40L) and the related molecules CD27 ligand (CD27), CD30 ligand (CD30L), and membrane TNF-alpha to stimulate B cell responses, expression of these proteins in the baculovirus system was performed. Sf9 cells expressing these membrane molecules were cultured with normal human B cells and a variety of B cell lines to assess the functional outcome. The signal provided by CD40L promotes aggregation of B cells, stimulates vigorous proliferation, and induces germ-line transcription of downstream heavy chain constant region genes in the absence of cytokine costimulation.

View Article and Find Full Text PDF

Engagement of CD40 by its ligand induces transcription of unrearranged Ig heavy chain genes, an initial step in switch recombination. The following studies were undertaken to understand the molecular basis of this response. Co-culture of S19 cells expressing membrane-bound CD40 ligand (CD40L) encoded by recombinant baculovirus with EBV-transformed B cell lines induced germline transcription of the epsilon gene in the absence of cytokines.

View Article and Find Full Text PDF

To study the role of CD27-CD27 ligand (CD27L)/CD70 interactions in the generation of murine allospecific T cell responses, SF9 cells or cell membranes expressing recombinant human CD70 were added to in vitro MLC containing C57BL/6 (H-2b) responder cells and class I and II MHC disparate H-2b/d stimulator cells. Alloantigen-specific CTL generation, CD8+ T cell proliferation, and levels of N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl esterase activity were enhanced in the presence of human CD27L/CD70 expressed on SF9 cell membranes. Enhancement of CD8+ T cell responses occurred in the absence of any discernible effects on CD4+ T cell proliferation or IL-2 responses.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_sessionvcd3eak0q9993mto3je6ongh5ualva9o): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once