Training and assessing convolutional neural network performance in automatic vascular segmentation using Ga-68 DOTATATE PET/CT.

To evaluate a convolutional neural network's performance (nnU-Net) in the assessment of vascular contours, calcification and PET tracer activity using Ga-68 DOTATATE PET/CT. Patients who underwent Ga-68 DOTATATE PET/CT imaging over a 12-month period for neuroendocrine investigation were included. Manual cardiac and aortic segmentations were performed by an experienced observer. Scans were randomly allocated in ratio 64:16:20 for training, validation and testing of the nnU-Net model. PET tracer uptake and calcium scoring were compared between segmentation methods and different observers. 116 patients (53.5% female) with a median age of 64.5 years (range 23-79) were included. There were strong, positive correlations between all segmentations (mostly r > 0.98). There were no significant differences between manual and AI segmentation of SUVmean for global cardiac (mean ± SD 0.71 ± 0.22 vs. 0.71 ± 0.22; mean diff 0.001 ± 0.008, p > 0.05), ascending aorta (mean ± SD 0.44 ± 0.14 vs. 0.44 ± 0.14; mean diff 0.002 ± 0.01, p > 0.05), aortic arch (mean ± SD 0.44 ± 0.10 vs. 0.43 ± 0.10; mean diff 0.008 ± 0.16, p > 0.05) and descending aorta (mean ± SD < 0.001; 0.58 ± 0.12 vs. 0.57 ± 0.12; mean diff 0.01 ± 0.03, p > 0.05) contours. There was excellent agreement between the majority of manual and AI segmentation measures (r ≥ 0.80) and in all vascular contour calcium scores. Compared with the manual segmentation approach, the CNN required a significantly lower workflow time. AI segmentation of vascular contours using nnU-Net resulted in very similar measures of PET tracer uptake and vascular calcification when compared to an experienced observer and significantly reduced workflow time.

Progressing Bevacizumab-Induced Diffusion Restriction Is Associated with Coagulative Necrosis Surrounded by Viable Tumor and Decreased Overall Survival in Patients with Recurrent Glioblastoma.

BACKGROUND AND PURPOSE: Patients with recurrent glioblastoma often exhibit regions of diffusion restriction following the initiation of bevacizumab therapy. Studies suggest that these regions represent either diffusion-restricted necrosis or hypercellular tumor. This study explored postmortem brain specimens and a population analysis of overall survival to determine the identity and implications of such lesions. MATERIALS AND METHODS: Postmortem examinations were performed on 6 patients with recurrent glioblastoma on bevacizumab with progressively growing regions of diffusion restriction. ADC values were extracted from regions of both hypercellular tumor and necrosis. A receiver operating characteristic analysis was performed to define optimal ADC thresholds for differentiating tissue types. A retrospective population study was also performed comparing the overall survival of 64 patients with recurrent glioblastoma treated with bevacizumab. Patients were separated into 3 groups: no diffusion restriction, diffusion restriction that appeared and progressed within 5 months of bevacizumab initiation, and delayed or stable diffusion restriction. An additional analysis was performed assessing tumor O6-methylguanine-DNA-methyltransferase methylation. RESULTS: The optimal ADC threshold for differentiation of hypercellularity and necrosis was 0.736 × 10-3mm2/s. Progressively expanding diffusion restriction was pathologically confirmed to be coagulative necrosis surrounded by viable tumor. Progressive lesions were associated with the worst overall survival, while stable lesions showed the greatest overall survival (P < .05). Of the 40% of patients with O6-methylguanine-DNA-methyltransferase methylated tumors, none developed diffusion-restricted lesions. CONCLUSIONS: Progressive diffusion-restricted lesions were pathologically confirmed to be coagulative necrosis surrounded by viable tumor and associated with decreased overall survival. Stable lesions were, however, associated with increased overall survival. All lesions were associated with O6-methylguanine-DNA-methyltransferase unmethylated tumors.

Oriented Gaussian mixture models for nonrigid 2D/3D coronary artery registration.

2D/3D registration of patient vasculature from preinterventional computed tomography angiography (CTA) to interventional X-ray angiography is of interest to improve guidance in percutaneous coronary interventions. In this paper we present a novel feature based 2D/3D registration framework, that is based on probabilistic point correspondences, and show its usefulness on aligning 3D coronary artery centerlines derived from CTA images with their 2D projection derived from interventional X-ray angiography. The registration framework is an extension of the Gaussian mixture model (GMM) based point-set registration to the 2D/3D setting, with a modified distance metric. We also propose a way to incorporate orientation in the registration, and show its added value for artery registration on patient datasets as well as in simulation experiments. The oriented GMM registration achieved a median accuracy of 1.06 mm, with a convergence rate of 81% for nonrigid vessel centerline registration on 12 patient datasets, using a statistical shape model. The method thereby outperformed the iterative closest point algorithm, the GMM registration without orientation, and two recently published methods on 2D/3D coronary artery registration.

First-line evaluation of coronary artery disease with coronary calcium scanning or exercise electrocardiography.

BACKGROUND: Although conventional (CAG) and computed tomography angiography (CTA) are reliable diagnostic modalities for exclusion of obstructive coronary artery disease (CAD), they are costly and with considerable exposure to radiation and contrast media. We compared the accuracy of coronary calcium scanning (CCS) and exercise electrocardiography (X-ECG) as less expensive and non-invasive means to rule out obstructive CAD. METHODS: In a rapid-access chest pain clinic, 791 consecutive patients with stable chest pain were planned to undergo X-ECG and dual-source CTA with CCS. According to the Duke pre-test probability of CAD patients were classified as low (<30%), intermediate (30-70%) or high risk (>70%). Angiographic obstructive CAD (>50% stenosis by CAG or CTA) was found in 210/791 (27%) patients, CAG overruling any CTA results. RESULTS: Obstructive CAD was found in 12/281 (4%) patients with no coronary calcium and in 73/319 (23%) with a normal X-ECG (p<0.001). No coronary calcium was associated with a substantially lower likelihood ratio compared to X-ECG; 0.11, 0.13 and 0.13 vs. 0.93, 0.55 and 0.46 in the low, intermediate and high risk group. In low risk patients a negative calcium score reduced the likelihood of obstructive CAD to less than 5%, removing the need for further diagnostic work-up. CCS could be performed in 754/756 (100%) patients, while X-ECG was diagnostic in 448/756 (59%) patients (p<0.001). CONCLUSIONS: In real-world patients with stable chest pain CCS is a reliable initial test to rule out obstructive CAD and can be performed in virtually all patients.

Phylogenetic and transcriptional analysis of a strictosidine synthase-like gene family in Arabidopsis thaliana reveals involvement in plant defence responses.

Protein domains with similarity to plant strictosidine synthase-like (SSL) sequences have been uncovered in the genomes of all multicellular organisms sequenced so far and are known to play a role in animal immune responses. Among several distinct groups of Arabidopsis thaliana SSL sequences, four genes (AtSSL4-AtSSL7) arranged in tandem on chromosome 3 show more similarity to SSL genes from Drosophila melanogaster and Caenorhabditis elegans than to other Arabidopsis SSL genes. To examine whether any of the four AtSSL genes are immune-inducible, we analysed the expression of each of the four AtSSL genes after exposure to microbial pathogens, wounding and plant defence elicitors using real-time quantitative RT-PCR, Northern blot hybridisation and Western blot analysis with antibodies raised against recombinant AtSSL proteins. While the AtSSL4 gene was constitutively expressed and not significantly induced by any treatment, the other three AtSSL genes were induced to various degrees by plant defence signalling compounds, such as salicylic acid, methyl jasmonate and ethylene, as well as by wounding and exposure to the plant pathogens Alternaria brassicicola and cucumber mosaic virus. Our data demonstrate that the four SSL-coding genes are regulated individually, suggesting specific roles in basal (SSL4) and inducible (SSL5-7) plant defence mechanisms.

Synergistic effect of 15-lipoxygenase 2 and radiation in killing head-and-neck cancer.

We previously demonstrated that 15-LOX-2 is significantly reduced in head and neck carcinoma and restoration of 15-LOX-2 expression results in tumor inhibition in HNC. The aim of this study is to evaluate 15-LOX-2 as a candidate for targeted radiotherapy. Molecular subcloning was performed to create a radiation-inducible 15-LOX-2 expression vector in which the full-length 15-LOX-2 cDNA was inserted downstream the recombinant Egr-1 promoter. The radiation-induced downregulations of 15-LOX-2 protein (twofold up) and its main metabolite 15S-HETE (threefold up) were observed in HNC cells transfected with the 15-LOX-2 expression vector after 4 Gy of radiation. Radiation-induced upregulation of 15-LOX-2 resulted in significant induction of apoptosis in HNC cells. Furthermore, survival colony formation was significantly reduced by 4 Gy in the HNC cells containing the 15-LOX-2 expression vector compared with the controls. Radiation-induced upregulation of 15-LOX-2 results in significant induction of apoptosis and enhances killing effect of radiotherapy in HNC. In addition, exogenous addition of 15S-HETE at high concentrations (>/=10 muM) but not at low concentrations induced upregulation of its endogenous ligand PPARgamma. In conclusion, synergistic effect between radiation and 15-LOX-2 was observed in killing HNC. 15-LOX-2 may be a potential target in radiation-targeted therapy of HNC. The 15-LOX-2 inhibition may not be PPARgamma dependent.

Paternal phenotype is associated with microalbuminuria in young adults with Type 1 diabetes mellitus of short duration.

AIMS: Susceptibility to diabetic nephropathy has not yet been causally linked to any genetic factors. We investigated in nuclear families whether parental ambulatory blood pressure, lipids and urine albumin excretion were early markers of risk of microalbuminuria in young adults with Type 1 diabetes. SUBJECTS AND METHODS: A subset of 98 young adults from the Oxford Regional Prospective Study were followed from diagnosis until aged >or= 16 years and duration of diabetes >or= 5 years (probands). Of these subjects, 24 developed microalbuminuria (males >or= 3.5 mg/mmol; females >or= 4 mg/mmol) and were designated cases, whereas 74 were controls. Family medical history, 24-h ambulatory blood pressure, urine albumin to creatinine ratio (ACR), non-fasting lipid profile and apolipoproteins (A1 and B) were measured in mothers and fathers. RESULTS: The prevalence of a parental hypertension (taking anti-hypertensive medication or daytime blood pressure > 140/90 mmHg), was similar in cases and controls (29% vs. 35%; chi2 test, P = 0.3). The systolic blood pressure night to day ratio and also ACR were higher in the fathers of cases when compared with the fathers of controls [systolic 0.88 (0.08), n = 14 vs. 0.85 (0.12), n = 53, P = 0.041]; [ACR median (IQ range) 0.6 mg/mmol (0.2-16.9) vs. 0.47 mg/mmol (0.3-3.7), P = 0.049]. Paternal night-time systolic blood pressure, night to day systolic blood pressure ratio and ACR were correlated with an index of susceptibility to albuminuria (r = 0.25, P = 0.042, n = 69 and r = 0.28, P = 0.022, n = 0.67 and r = 0.24, P = 0.029, n = 0.85, respectively). CONCLUSIONS: Higher paternal ACR and night to day ratio of ambulatory blood pressure, but not parental hypertension or maternal factors, are associated with microalbuminuria in young adults with Type 1 diabetes.

Role of adipocyte differentiation-related protein in surfactant phospholipid synthesis by type II cells.

Adipocyte differentiation-related protein (ADrP) is an intrinsic lipid storage droplet protein that is highly expressed in lung. ADrP localizes to lipid storage droplets within lipofibroblasts, pulmonary cells characterized by high triacylglycerol, which is a precursor for surfactant phospholipid synthesis by alveolar type II epithelial (EPII) cells. The developmental pattern of ADrP mRNA and protein expression in lung tissue parallels triacylglycerol accumulation in rat lung. ADrP mRNA levels are relatively high in isolated lipofibroblasts, accounting for the high ADrP expression in lung. Isolated EPII cells, which do not store neutral lipids but derive them from lipofibroblasts, have low levels of ADrP mRNA expression. ADrP is found around lipid droplets in cultured lipofibroblasts, but not in EPII cells isolated from developing rat lung. After coculture with lipofibroblasts, EPII cells acquired ADrP, which associates with lipid droplets. Furthermore, (3)H-labeled triolein in isolated ADrP-coated lipid droplets is a tenfold better substrate for surfactant phospholipid synthesis by cultured EPII cells than (3)H-labeled synthetic triolein alone. Antibodies to ADrP block transfer of neutral lipid. These data suggest a role for ADrP in this novel mechanism for the transfer of lipid between lipofibroblasts and EPII cells.

The complex structures of arabinogalactan-proteins and the journey towards understanding function.

Arabinogalactan-proteins (AGPs) are a family of complex proteoglycans found in all higher plants. Although the precise function(s) of any single AGP is unknown, they are implicated in diverse developmental roles such as differentiation, cell-cell recognition, embryogenesis and programmed cell death. DNA sequencing projects have made possible the identification of the genes encoding a large number of putative AGP protein backbones. In contrast, our understanding of how AGPs undergo extensive post-translational modification is poor and it is important to understand these processes since they are likely to be critical for AGP function. Genes believed to be responsible for post-translational modification of an AGP protein backbone, include prolyl hydroxylases, glycosyl transferases, proteases and glycosylphosphatidylinositol-anchor synthesising enzymes. Here we examine models for proteoglycan function in animals and yeast to highlight possible strategies for determining the function(s) of individual AGPs in plants.

Blood pressure does not rise before the onset of microalbuminuria in children followed from diagnosis of type 1 diabetes. Oxford Regional Prospective Study Group.

OBJECTIVE: To examine whether a rise in blood pressure could be detected before the onset of microalbuminuria (MA) in a cohort of children followed from diagnosis of type 1 diabetes. RESEARCH DESIGN AND METHODS: The Oxford Regional Prospective Study is an incident cohort study of children with type 1 diabetes aged (mean +/- SD) 9.8 +/- 3.7 years at diagnosis. Subjects were assessed annually from diagnosis, with measurement of HbA1c, arterial blood pressure (random zero), and three urine samples for estimation of the albumin/creatinine ratio. During follow-up, 63 of 494 children developed MA at one or more annual assessments and were designated as cases for a nested case-control study. Each case was matched for sex and age at diagnosis with two normoalbuminuric control subjects. Blood pressure (BP) data were compared at corresponding years of diabetes duration. RESULTS: Cases with MA were similar to normoalbuminuric control subjects with respect to age and BMI, but they had higher mean HbA1c levels (mean difference 1.1%, P < 0.001). In the years before the onset of MA, the diastolic BP standard deviation score (SDS) was significantly higher than zero in cases (mean 0.49, P < 0.001) and in control subjects (0.50, P < 0.001). No difference could be detected between cases and control subjects before the onset of MA in either systolic or diastolic BP (mean difference systolic -1.2 mmHg [95% CI -4.7 to 2.7], mean difference diastolic 0.1 mmHg [-2.4 to 2.6]). However, within the cases, the onset of MA was associated with elevations in systolic and diastolic BP SDSs (F = 16.1, P < 0.001; and F = 18.0, P < 0.001). BMI, but not HbA1c, was associated with systolic and diastolic BP SDSs in the subjects with MA (F = 0.6, P = 0.4; and F = 12.3, P = 0.001). However, the association of BP with MA remained signifcant for systolic BP (P = 0.001) and for diastolic BP (P < 0.001) after adjusting for BMI. CONCLUSIONS: A rise in systemic BP cannot be detected before the first appearance of MA in children with type 1 diabetes. BP rises concurrently with the onset of MA and is also closely related to BMI.

Markers of renal tubular dysfunction measured annually do not predict risk of microalbuminuria in the first few years after diagnosis of Type I diabetes.

AIMS/HYPOTHESIS: Early detection of risk of microalbuminuria could prevent early renal damage. We investigated whether urine retinol binding protein and N-acetyl-glucosaminidase could predict the risk of microalbuminuria in a large cohort of children followed from diagnosis of Type I (insulin-dependent) diabetes mellitus. METHODS: Subjects under 16 years of age within a georaphically defined region were recruited at diagnosis of Type I (insulin-dependent) diabetes mellitus. Annually, albumin-, retinol binding protein- and N-acetyl-glucosaminidase- to creatinine ratios were each measured in 3 urine samples. RESULTS: A total of 511 subjects were followed for a median of 6 years (range: 1-14). Microalbuminuria (males: > or = 3.5 mg/mmol; females: > or = 4.0 mg/mmol, in 2 out of 3 urines) developed in 78 subjects (36 male). The cumulative probability of microalbuminuria was 40% after 12 years duration of diabetes. Retinol-binding-proteinuria (men: > or = 21 microg/mmol; women > or = 33 microg/mmol) developed in 217 subjects (152 men). The cumulative probability of retinol-binding-proteinuria was 67 % after 12 years duration of diabetes. The cumulative probability of retinol-binding-proteinuria was 40 % before the onset of microalbuminuria and 59% in subjects who did not subsequently develop microalbuminuria. Retinol-binding-proteinuria developed at a higher rate with increasing HbA1c than microalbuminuria. N-acetyl-glucosaminidase-uria (males: > or = 56 micromol-pnp x h(-1) x mmol(-1); females: > or = 46 micromol-pnp h(-1) x mmol(-1)) developed in 477 subjects. The cumulative probability of N-acetylglucosaminidase-uria was 98 % after 10 years of diabetes duration. The cumulative probability of N-acetyl-glucosaminidase-uria was 73 % in the years before the onset of microalbuminuria and 97 % in subjects without microalbuminuria. The probability of Nacetyl-glucosaminidase-uria was 99 % with an HbA1c greater than or equal to 14.5 %. CONCLUSIONS/INTERPRETATION: Raised amounts of urine retinol binding protein and N-acetyl-glycosaminidase are related to HbA1c and the duration of diabetes. They occur in the majority of subjects and are not early markers for the risk of microalbuminuria.

Effect of denaturants on the emulsifying activity of proteins.

The relationship between protein flexibility and emulsifying activity was investigated by disrupting disulfide bonds and/or noncovalent interactions of the protein. Oil-in-water emulsions using model proteins (apomyoglobin, beta-casein, alpha-casein, lysozyme, bovine serum albumin, kappa-casein, and beta-lactoglobulin) were made in the presence of chemical denaturants (dithiothreitol and/or urea). In most cases, the presence of denaturants enhanced emulsifying activity. The effect was protein-specific and depended on the relative importance of disulfide bonds and noncovalent interactions in stabilizing the native conformation of each protein. Implications for the design of novel protein emulsifiers are discussed.

Risk of nephropathy can be detected before the onset of microalbuminuria during the early years after diagnosis of type 1 diabetes.

OBJECTIVE: The early detection of a rise in albumin excretion within the normal range could permit early intervention to prevent the development of microalbuminuria (MA) in genetically susceptible subjects with type 1 diabetes. In the Oxford Regional Prospective Study we prospectively examined urine albumin excretion during the first years after diagnosis of childhood type 1 diabetes. RESEARCH DESIGN AND METHODS: Between 1986 and 1995, 511 subjects aged < 16 years were recruited at diagnosis and followed for a median of 6 years (range 1-14). In 78 subjects (designated cases), an annual assessment of the albumin-to-creatinine ratio (ACR) in three morning first-void urine samples detected MA (males: ACR > or =3.5 mg/mmol, females: ACR > or =4.0 mg/mmol in two of three urine samples). In 63 of these subjects and 396 normoalbuminuric diabetic control subjects, rates of change of the ACR were calculated as the slope of the ACR over diabetes duration. RESULTS: The baseline ACR (median [interquartile (IQ) range]), as measured at 1-2.5 years' duration of diabetes, was higher in microalbuminuric subjects than in the normoalbuminuric subjects (1.0 mg/mmol [0.6-2.1], n = 52, vs. 0.8 mg/mmol [0.6-1.2], n = 303; P = 0.02). The rate of increase of the ACR in the years before the onset of MA was higher in the microalbuminuric subjects than in the normoalbuminuric subjects (70% per year [37-149], n = 63, vs. 1% per year [-9 to 13], n = 396; P < 0.001). The mean HbA1c level after the onset of puberty was weakly correlated with the rate of change of the ACR (r = 0.11, P = 0.024, n = 418). CONCLUSIONS: Higher levels of ACR within the first 2 years after diagnosis and a significantly higher rate of increase of the ACR within the first 5 years from diagnosis can be detected in subjects who subsequently develop MA. HbA1c is a determinant of risk for MA, but pubertal factors have a greater effect on rates of progression of urine albumin excretion during adolescence in this cohort.

The classical arabinogalactan protein gene family of arabidopsis.

Arabinogalactan proteins (AGPs) are extracellular proteoglycans implicated in plant growth and development. We searched for classical AGPs in Arabidopsis by identifying expressed sequence tags based on the conserved domain structure of the predicted protein backbone. To confirm that these genes encoded bona fide AGPs, we purified native AGPs and then deglycosylated and deblocked them for N-terminal protein sequencing. In total, we identified 15 genes encoding the protein backbones of classical AGPs, including genes for AG peptides-AGPs with very short backbones (10 to 13 amino acid residues). Seven of the AGPs were verified as AGPs by protein sequencing. A gene encoding a putative cell adhesion molecule with AGP-like domains was also identified. This work provides a firm foundation for beginning functional analysis by using a genetic approach.

Freezing method affects the concentration and variability of urine proteins and the interpretation of data on microalbuminuria. The Oxford Regional Prospective Study Group.

AIMS: Microalbuminuria and, to a lesser extent, renal tubular proteins are widely used in the early detection of incipient nephropathy in diabetes mellitus. Recent reports have indicated detrimental effects of storage at -20 degrees C on urine proteins. This study investigated the effects of storage on the measurement of urine proteins and discusses implications for the interpretation of data. METHODS: Two-hundred and sixty-eight specimens, collected from children with Type 1 diabetes, split into duplicate aliquots and stored at -20 degrees C and -70 degrees C, respectively, for 6-8 months, were analysed for albumin, retinol binding protein, N-acetyl glucosaminidase and creatinine, in the same assays to eliminate inter-assay variability. Two independent non-diabetic cohorts of children provided urine specimens, which were stored at -20 degrees C for one cohort and -70 degrees C for the other, to determine normal ranges for urine proteins. RESULTS: Storage at -20 degrees C led to a variable underestimation of all three urine proteins in 20% of specimens. Creatinine was unaffected. This underestimation was greater in more concentrated urine (r2 = 0.38, P < 0.001, n = 262). Consequently storage at -20 degrees C increased the variance of the albumin/ creatinine ratio more than the variance of albumin concentration. Temperature of storage affected the normal range, which was 0.1-2.1 mg/mmol at -20 degrees C compared to 0.3-3.1 mg/mmol at -70 degrees C. The prevalence of microalbuminuria (> 2SD above the geometric mean in non-diabetic specimens stored at -20 degrees C) was 27% after storage at -70 degrees C vs. 24% after -20 degrees C. The prevalence of microalbuminuria (>2SD above the geometric mean in nondiabetic specimens stored at -70 degrees C) was 21% after storage at -70 degrees C vs. 17% after -20 degrees C. CONCLUSIONS: Urine proteins are significantly but variably underestimated after storage at -20 degrees C. These effects account for increased variance and differences in the normal range, but have less effect on the detection of microalbuminuria than might be predicted.

Adrenal and liver in normal and cld/cld mice synthesize and secrete hepatic lipase, but the lipase is inactive in cld/cld mice.

Combined lipase deficiency (cld) is a recessive mutation in mice that causes a severe lack of lipoprotein lipase (LPL) and hepatic lipase (HL) activities, hyperlipemia, and death within 3 days after birth. Earlier studies showed that inactive LPL and HL were synthesized by cld/cld tissues and that LPL synthesized by cld/cld brown adipocytes was retained in their ER. We report here a study of HL in liver, adrenal, and plasma of normal newborn and cld/cld mice. Immunofluorescence studies showed HL was present in extracellular space, but not in cells, in liver and adrenal of both normal and cld/cld mice. When protein secretion was blocked with monensin, HL was retained intracellularly in liver cell cultures and in incubated adrenal tissues of both groups of mice. These findings demonstrated that HL was synthesized and secreted by liver and adrenal cells in normal newborn and cld/cld mice. HL activities in liver, adrenal, and plasma in cld/cld mice were very low, <8% of that in normal newborn mice, indicating that HL synthesized and secreted by cld/cld cells was inactive. Livers of both normal newborn and cld/cld mice synthesized LPL, but the level of LPL activity in cld/cld liver was very low, <9% of that in normal liver. Immunofluorescence studies showed that LPL was present intracellularly in liver of cld/cld mice, indicating that LPL was synthesized but not secreted by cld/cld liver cells. Immunofluorescent LPL was not found in normal newborn liver cells unless the cells were treated with monensin, thus demonstrating that normal liver cells synthesized and secreted LPL. Livers of both groups of mice contained an unidentified alkaline lipase activity which accounted for 34-54% of alkaline lipase activity in normal and 65% of that in cld/cld livers. Our findings indicate that liver and adrenal cells synthesized and secreted HL in both normal newborn and cld/cld mice, but the lipase was inactive in cld/cld mice. That cld/cld liver cells secreted inactive HL while retaining inactive LPL indicates that these closely related lipases were processed differently.

Perilipins, ADRP, and other proteins that associate with intracellular neutral lipid droplets in animal cells.

Although all animal cells package and store neutral lipids in discrete intracellular storage droplets, there is little information on the molecular processes that govern either the deposition or catabolism of the stored lipid components. Studies on adipocytes have uncovered the perilipins and ADRP, related proteins that appear to be intrinsic to the surfaces of intracellular lipid storage droplets. We discuss the properties, distribution, localization, and potential functions of these proteins, as well as those of vimentin and the recently-described 'capsular' proteins, in lipid storage and metabolism.