1 LAL can be specifically inhibited by a variety of 3,4-di
2 LAL defects cause Wolman disease (WD) and CE storage dis
3 LAL deficiency causes expansion of CD11b(+)Gr-1(+) immat
4 LAL deficiency impaired T cell development in the thymus
5 LAL is encoded by LIPA (10q23.31) and the most common mu
6 A mouse model with
a LAL null mutation was produced by targeting disruption o
7 Humans and mice with defective or
absent LAL activity accumulate large amounts of cholesteryl est
8 An LAL null (lal-/-) mouse model closely mimics human WD/CE
9 , and 30 minutes using limulus lysate
assay (
LAL) and EndoCAb Ig assays.
10 cid (EDTA); limulus amoebocyte lysate
assay (
LAL); pertussis toxin (PTX); forward scatter (FSC); Inte
11 ed with the initial refractive target
before LAL implantation.
12 stiffness in control strips to levels
beyond LAL specimens.
13 To test how myeloid
cell LAL controls myelopoiesis and lymphopoiesis, a myeloid-s
14 Myeloid
cell LAL expression improved the proliferation and function o
15 n the thymus, reconstitution of myeloid
cell LAL restored development of thymocytes at the double-neg
16 using a commercially available
colorimetric LAL assay.
17 Patients
completing LAL-CL01 were eligible to enroll in the extension study
18 o disease formation in various organs
during LAL deficiency.
19 Following LAL, myocardial stresses at given strains and circumfere
20 These studies provide feasibility
for LAL enzyme therapy in human WD and CESD.
21 We present a mechanism
for LAL inhibition by these compounds whereby LAL transientl
22 cal trials of enzyme replacement therapy
for LAL deficiency are currently being developed.
23 ECs
from LAL-deficient (lal(-/-)) mice possess enhanced prolifera
24 that metabolic reprogramming resulting
from LAL deficiency enhances the ability of ECs to stimulate
25 Furthermore,
LAL-deficient mice challenged with RE gavage exhibited l
26 To assess
how LAL in lung epithelial cells plays a role in this inflam
27 Comparisons of mouse and
human LAL genes organization revealed identical intron/exon bo
28 nsgenic system was generated to induce
human LAL (hLAL) expression in the lal-/- genetic background u
29 Myeloid-specific expression of
human LAL (hLAL) in lal(-/-) mice rescues these malignant phen
30 yte, hepatocyte-specific expression of
human LAL (hLAL) in lal(-/-) mice was established by cross-bre
31 epithelial cell-specific expression of
human LAL (hLAL) in Lipa(-/-) mice was established by crossbre
32 effects and safety of the recombinant
human LAL, sebelipase alfa, nine patients received four once-w
33 py was tested using mannose terminated
human LAL expressed in Pichia pastoris (phLAL), purified, and
34 oligosaccharide chains was tested with
human LAL expressed in Pichia pastoris (phLAL) and CHO cells (
35 rinsic expression of the lysosomal
hydrolase LAL (lysosomal acid lipase) to mobilize FA for FAO and m
36 In LAL gene-knockout (lal(-/-)) mice, blockage of cholester
37 ekly infusions (0.35, 1, or 3 mg.kg(-1) )
in LAL-CL01, which is the first human study of this investi
38 e hypothesized that ECs are dysfunctional
in LAL-deficient (lal(-/-)) mice.
39 MDSCs or mTOR to rejuvenate EC functions
in LAL deficiency-related diseases.
40 One major manifestation
in LAL-deficient (Lipa(-/-)) mice is an increase of tumor g
41 ent, LV stresses and stiffness normalized
in LAL specimens and microtubule density following colchici
42 Transaminases decreased in patients
in LAL-CL01 and increased between studies.
43 density following colchicine was similar
in LAL to control.
44 ceiving ongoing sebelipase alfa treatment
in LAL-CL04, the mean +/- standard deviation (SD) decreases
45 t week 12 compared to the baseline values
in LAL-CL01 were 46 +/- 21 U/L (-52%) and 21 +/- 14 U/L (-3
46 Interestingly,
LAL-deficient mice exhibited increased RE content in the
47 lysosomal acid lipase (hLAL) expression
into LAL gene knockout (lal(-/-)) mice.
48 ly used for endotoxin level determination
is LAL (Limulus Amebocyte Lysate) assay.
49 igh Risk Adult Acute Lymphoblastic
Leukemia [
LAL-AR/2003]) assigned adolescent and adult patients (ag
50 ton stage 27 following left atrial
ligation (
LAL) at stage 21 to reduce LV volume load and create lef
51 ding, CTB) or reduced (left atrial
ligation,
LAL) hemodynamic loading of the embryonic heart.
52 Our observations
link LAL to metabolic reprogramming in lymphocytes and show t
53 Lysosomal acid
lipase (
LAL) cleaves cholesteryl esters and triglycerides to gen
54 Lysosomal acid
lipase (
LAL) cleaves cholesteryl esters and triglycerides to gen
55 lying mechanisms that lysosomal acid
lipase (
LAL) deficiency causes infiltration of myeloid-derived s
56 Lysosomal acid
lipase (
LAL) deficiency causes systemic expansion and infiltrati
57 Of note, lysosomal acid
lipase (
LAL) deficiency facilitates melanoma growth and metastas
58 Lysosomal acid
lipase (
LAL) has been recently identified as a potential therape
59 Lysosomal acid
lipase (
LAL) hydrolyzes cholesteryl esters and triglycerides to
60 Lysosomal acid
lipase (
LAL) is a key enzyme that cleaves cholesteryl esters and
61 Lysosomal acid
lipase (
LAL) is essential for the clearance of endocytosed chole
62 Lysosomal acid
lipase (
LAL) is essential for the hydrolysis of cholesteryl este
63 Lysosomal acid
lipase (
LAL) is essential for the hydrolysis of the triglyceride
64 Lysosomal acid
lipase (
LAL) is required for the hydrolysis of intracellular cho
65 Lysosomal acid
lipase (
LAL) is the critical enzyme for the hydrolysis of the tr
66 Lysosomal acid
lipase (
LAL) is the critical enzyme for the hydrolysis of trigly
67 bsequent lipolysis by lysosomal acid
lipase (
LAL) was important for the engagement of elevated oxidat
68 Lysosomal acid
lipase (
LAL), a key enzyme in the metabolic pathway of neutral l
69 herited deficiency of lysosomal acid
lipase (
LAL), is an underappreciated cause of progressive liver
70 deficient activity of lysosomal acid
lipase (
LAL).
71 lalistat, a specific lysosomal acid
lipase (
LAL/Lipa) inhibitor on LD degradation in HSCs during act
72 Deficiency of lysosomal acid
lipase (
LAL; official name Lipa, encoded by Lipa) in mice (lal(-
73 s we examined neonatal levator auris
longus (
LAL) and 4th deep lumbrical (4DL) muscles, as well as ad
74 ersus abdominis (TVA), levator auris
longus (
LAL) and lumbrical muscles were disrupted in both mouse
75 In the
lung,
LAL is highly expressed in alveolar type II epithelial c
76 as assayed in the Limulus amebocyte
lysate (
LAL) test.
77 ility to coagulate Limulus amebocyte
lysate (
LAL).
78 dotoxin using the limulus amebocyte
lystate (
LAL) gel clot method.
79 In this study, we found that
murine LAL exhibits RE hydrolase activity.
80 zygote knockout mice (lal -/lal-) produce
no LAL mRNA, protein or enzyme activity.
81 +/lal- mice have approximately 50% of
normal LAL activity and do not show lipid accumulation.
82 Through week 12
of LAL-CL04, these seven patients also showed mean decrease
83 The unparalleled recognition abilities
of LAL biosensors perched with remarkable sensitivity, high
84 acological inhibition or genetic ablation
of LAL in murine liver largely reduced in vitro acid RE hyd
85 urring in the tested sample upon addition
of LAL.
86 Western blot analysis
of LAL embryos showed an increase in both total and polymer
87 The coagulation
of LAL is commonly used to signal the presence of endotoxin
88 To understand that the expression
of LAL mRNA and protein is tissue and cell specifically reg
89 Pharmacological inhibition
of LAL in the human hepatocyte cell line HepG2, incubated w
90 mides, esters, and ketones for inhibition
of LAL.
91 azole carbamates are effective inhibitors
of LAL.
92 To test the functional role
of LAL in hepatocyte, hepatocyte-specific expression of hum
93 ice provide a model to determine the role
of LAL in lipid metabolism and the pathogenesis of its defi
94 also contain retinyl esters (REs), a role
of LAL in the clearance of endocytosed REs has not been rep
95 These results indicate a crucial role
of LAL-regulated mTOR signaling in the production and funct
96 only approximately 3%-5% of normally
spliced LAL.
97 e eligible to enroll in the extension
study (
LAL-CL04) in which they again received four once-weekly
98 with a history of laser refractive
surgery,
LAL implantation and postimplantation adjustment provide
99 These results support a concept
that LAL in hepatocytes is a critical metabolic enzyme in con
100 These results support a concept
that LAL is a critical metabolic enzyme in lung epithelial ce
101 These studies demonstrate
that LAL in myeloid cells plays a critical role in maintainin
102 These results provide evidence
that LAL is an important regulator of myelopoiesis during hem
103 Our results indicate
that LAL has a critical role in regulating MDSCs' ability to
104 In summary, our results indicate
that LAL is the major acid RE hydrolase and required for func
105 Our results indicate
that LAL regulates EC functions through interaction with MDSC
106 dial circulating RE content, indicating
that LAL is required for efficient nutritional vitamin A avai
107 Our data suggest
that LAL/Lipa is involved in the degradation of a specific pr
108 The LAL endotoxin detection limit for samples dispersed in C
109 liposomes, but did not appear to affect
the LAL assay sensitivity once the liposomes were completely
110 t not DSPG, at 10 mol% further decreased
the LAL endotoxin detection limit.
111 Mice double homozygous for
the LAL and MMR deficiences (lal-/-;MMR-/-) showed phLAL upt
112 In
the LAL-deficient (lal(-/-)) mouse model, melanoma metastasi
113 L to consume unpolymerized macromeres in
the LAL.
114 ultraviolet light to alter the shape of
the LAL and hence its refractive power.
115 solubilization and/or the sensitivity of
the LAL assay.
116 A targeted disruption of
the LAL locus produced a null (lal( -/-)) mouse model that m
117 tor neurons in the caudal muscle band of
the LAL.
118 ents, we applied 2 lock-in treatments to
the LAL to consume unpolymerized macromeres in the LAL.
119 ation in HSCs during activation in vitro
The LAL inhibitor increased the levels of TAG, cholesteryl e
120 l refractive surgery were implanted with
the LAL during cataract surgery performed at a single clinic
121 Therefore,
LAL, its downstream genes, and lipid mediators all play
122 ral TVA muscle compared with the fast-
twitch LAL and lumbrical muscles.
123 re HPS function relative to controls
whereas LAL was associated with delayed conversion to apical ini
124 or LAL inhibition by these compounds
whereby LAL transiently carbamoylates the enzyme similarly to pr
125 aching significance (P=0.061) were seen
with LAL only.