Prevalence of incidental narrowing of the superior segment of the internal jugular vein in patients without multiple sclerosis.

PURPOSE: Internal jugular vein (IJV) narrowing superiorly is likely relatively frequent. IJV narrowing has been proposed as a potential pathophysiologic component for multiple sclerosis (MS). Our purpose was to investigate the prevalence of incidental superior IJV narrowing in patients imaged with neck computed tomography angiography (CTA) for reasons unrelated to IJV pathology or MS. METHODS: We retrospectively identified 164 consecutive adult patients who had undergone neck CTA in which at least one IJV superior segment was opacified (158 right, 155 left IJVs). At the narrowest point of the upper IJV, each IJV was assessed for dominance, graded (shape and narrowing), measured (diameter and area), and located (axially and craniocaudally). Associations were analyzed using Spearman rank correlations (p < 0.05 significant). Medical records were reviewed for MS. RESULTS: Among 164 patients, at least one IJV was: absent/pinpoint in 15 % (25/164), occluded/nearly occluded in 26 % (43/164). Shape, narrowing, and the three measurements all correlated with each other (all p < 0.01). Lateral location with respect to C1 transverse foramen correlated with subjectively and objectively smaller IJVs (p < 0.01). The most common craniocaudal location was at the C1 transverse process (79 % (125/158) of right and 81 % (126/155) of left IJVs). No patient had a diagnosis of MS. CONCLUSIONS: The appearance of the superior IJV is variable, with an occlusive/near-occlusive appearance present in approximately one-quarter of patients without known MS undergoing CTA. Radiologists should be aware of and cautious to report or ascribe clinical significance to this frequent anatomic variant.

Facet joint signal change on MRI at levels of acute/subacute lumbar compression fractures.

BACKGROUND AND PURPOSE: The prevalence of facet joint signal change in acute/subacute lumbar vertebral body compression fractures is unknown. We hypothesized that facet joint signal change on MR imaging is more common in facet joints associated with an acute/subacute lumbar compression fracture than those associated with normal vertebral bodies or ones that have a chronic compression fracture. MATERIALS AND METHODS: Three neuroradiologists and a neuroradiology fellow retrospectively graded facet joint inflammatory change on MR imaging in 900 facet joints in 75 patients with at least 1 painful osteoporotic lumbar compression fracture. Facet joint signal change was assessed on T2-weighted images with chemical fat-saturation, STIR images, and/or gadolinium-enhanced T1-weighted images with chemical fat-saturation. Each facet joint from the T12/L1 to L5/S1 level was assessed individually. An overall facet joint signal-change score, which is a composite measure of the grade of signal change for all 4 facet joints associated with a given lumbar vertebral level, was devised, and statistical significance was assessed via Wilcoxon rank sum tests. RESULTS: The overall facet joint signal-change scores were significantly higher at vertebral body levels affected by an acute/subacute compression fracture compared with control levels, which were associated with either normal bodies or chronic compression fractures. CONCLUSIONS: Our findings suggest an association between facet joint signal change on MR imaging and acute/subacute lumbar vertebral body compression fractures.

Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM).

Patients with multiple myeloma progressing on current therapies have limited treatment options. Pomalidomide (CC4047), an immunomodulatory drug, has significant activity in relapsed myeloma and previous studies suggest activity in lenalidomide refractory disease. To better define its efficacy in this group, we treated a cohort of lenalidomide refractory patients. Pomalidomide was given orally (2 mg) daily, continuously in 28-day cycles along with dexamethasone (40 mg) given weekly. Responses were assessed by the International Myeloma Working Group Criteria. Thirty-four patients were enrolled. The best response was very good partial response in 3 (9%), partial response (PR) in 8 (23%), best responses (MR) in 5 (15%), stable disease in 12 (35%) and progressive disease in 6 (18%), for an overall response rate of 47%. Of the 14 patients that were considered high risk, 8 (57%) had responses including 4 PR and 4 MR. The median time to response was 2 months and response duration was 9.1 months, respectively. The median overall survival was 13.9 months. Toxicity was primarily hematologic, with grade 3 or 4 toxicity seen in 18 patients (53%) consisting of anemia (12%), thrombocytopenia (9%) and neutropenia (26%). The combination of pomalidomide and dexamethasone (Pom/dex) is highly active and well tolerated in patients with lenalidomide-refractory myeloma.

Fractional oxidation of chylomicron-derived oleate is greater than that of palmitate in healthy adults fed frequent small meals.

Differences in oxidation of individual dietary fatty acids could contribute to the effect of dietary fat composition on risk factors for non-insulin-dependent diabetes mellitus and cardiovascular disease. Using a novel stable isotope technique, we compared fractional oxidation of chylomicron-derived oleate and palmitate in 10 healthy adults in a crossover study. 1-(13)C-labeled oleate or palmitate was emulsified into a eucaloric formula diet administered each 20 min for 7 h to produce a plateau in excretion of (13)C label in breath CO(2). Unlabeled oleate and palmitate each provided 16% of dietary energy, and other fatty acids provided 8% of energy. Total dietary fat was 40% of energy, carbohydrate was 46%, and protein was 14%. Diet without tracer was fed for 2 h before beginning tracer administration to establish a baseline fed state. Relative oxidation of oleate versus palmitate was defined as fractional oxidation of oleate divided by fractional oxidation of palmitate. Relative oxidation averaged 1.21 (99.5% confidence interval = 1.03;-1.39), indicating that fractional oxidation of oleate was significantly greater than that of palmitate.

Glucose-6-phosphate dehydrogenase from Saccharomyces cerevisiae is a glycoprotein.

A commercial preparation of glucose-6-phosphate dehydrogenase (G6PD) purified from Saccharomyces cerevisiae was subjected to PAGE analysis under both nondenaturing and denaturing conditions. The enzyme, identified by both activity staining and anti-yeast G6PD antibody immunoblotting, was shown to contain carbohydrate using the highly specific periodate-digoxigenin antidigoxigenin method which is diagnostic for glycoproteins.

Advances in molecular biology: implications for the future of clinical nutrition practice.

Advances in molecular biology during the past decade have substantially contributed to our understanding of how genes influence physiologic processes and, ultimately, our health. Genes associated with many nutrition-related chronic diseases are being identified and characterized. Nutrients may directly or indirectly influence the transcription and/or translation of specific gene products. Identifying genetic markers for specific diseases and exploring gene therapy will provide new opportunities and challenges for clinical nutrition practice in the 21st century. Nutrition practitioners must be cognizant of developments in molecular biology to meet the challenges of providing nutrition care in the future.

Depletion and repletion of biotinyl enzymes in liver of biotin-deficient rats: evidence of a biotin storage system.

The quantities of biotinyl proteins in liver of young rats were compared with age-matched controls at intervals during depletion and repletion of biotin. Growth rate and the concentrations of biotinyl proteins previously proposed as mitochondrial storage forms of acetyl CoA carboxylase rapidly decreased in response to biotin deprivation, whereas neither the concentration nor activity of cytosolic acetyl CoA carboxylase was affected. Concentrations of carboxylases active within mitochondria (pyruvate carboxylase, propionyl CoA carboxylase and 3-methyl crotonyl CoA carboxylase) decreased only after d 28. When biotin was injected into biotin-deficient rats, concentrations of the carboxylases active within mitochondria were restored to control levels within 3 h, whereas the concentrations of putative mitochondrial storage forms of acetyl CoA carboxylase reached normal levels only after 9 h, indicating that the injected biotin was preferentially used for the synthesis of the carboxylases active within mitochondria rather than acetyl CoA carboxylase. Mitochondrial acetyl CoA carboxylase may serve as a reservoir to maintain a normal concentration of cytosolic acetyl CoA carboxylase in liver of rats deprived of biotin and provide biotin, indirectly, to maintain essentially normal concentrations of the biotinyl enzymes active within mitochondria for several weeks after rats were fed a biotin-deficient diet.

Mitochondrial acetyl-CoA carboxylase. Time course of mobilization/activation in liver of refed rats.

Fasted (48 h) rats were killed at 0, 2, 4, 6, 8, 12, 16, 20 and 24 h after they were refed on a high-carbohydrate diet. An increase in the maximal activity and quantity of cystolic acetyl-CoA carboxylase was found in liver of refed rats after a lag time of about 8 h. The increased quantity of cytosolic enzyme was attributable primarily to mobilization of mitochondrial storage forms and not to substantial increase in the rate of synthesis of acetyl-CoA carboxylase.

Mitochondrial storage forms of acetyl CoA carboxylase: mobilization/activation accounts for increased activity of the enzyme in liver of genetically obese Zucker rats.

In earlier reports, we have described a previously unrecognized mechanism which regulates the activity of acetyl CoA carboxylase in rat liver by the control of its distribution between relatively inactive mitochondrial and active cytosolic forms. In this study, the activity, total quantity and the subcellular distribution of acetyl CoA carboxylase were determined in liver of fed and fasted (48 h) homozygous obese (fa/fa) zucker rats and homozygous lean (Fa/Fa) littermates. The results indicate that neither diet nor genetic obesity affected the total quantity of acetyl CoA carboxylase per unit weight of liver. Instead, increased activity of this enzyme in the liver of the Zucker rat was primarily due to a shift in the subcellular distribution away from relatively inactive mitochondrial forms toward active cytosolic forms. Thus, the Zucker rat appears to be yet another example illustrating the physiological importance of regulating the activity of acetyl CoA carboxylase by controlling its subcellular distribution.

Bovine milk-fat-globule membrane contains an enzymically inactive form of acetyl-CoA carboxylase.

Enzymically inactive acetyl-CoA carboxylase [acetyl-CoA:carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] was found as a component of bovine milk-fat-globule membrane (MFGM). Acetyl-CoA carboxylase was present in MFGM at a higher concentration than in cytosolic or mitochondrial fractions of bovine mammary tissue, which makes it unlikely that its presence was due to simple contamination by these subcellular constituents.

Enzymatically inactive forms of acetyl-CoA carboxylase in rat liver mitochondria.

Biotinyl proteins were labelled by incubation of SDS-denatured preparations of subcellular fractions of rat liver with [14C]methylavidin before polyacrylamide-gel electrophoresis. Fluorographic analysis showed that mitochondria contained two forms of acetyl-CoA carboxylase [acetyl-CoA:carbon dioxide ligase (ADP-forming) EC 6.4.1.2], both of which were precipitated by antibody to the enzyme. When both forms were considered, almost three-quarters of the total liver acetyl-CoA carboxylase was found in the mitochondrial fraction of liver from fed rats while only 3.5% was associated with the microsomal fraction. The remainder was present in cytosol, either as the intact active enzyme or as a degradation product. The actual specific activity of the cytosolic enzyme was approx. 2 units/mg of acetyl-CoA carboxylase protein while that of the mitochondrial enzyme was about 20-fold lower, indicating that mitochondrial acetyl-CoA carboxylase was relatively inactive. Fractionation of mitochondria with digitonin showed that acetyl-CoA carboxylase was associated with the outer mitochondrial membrane. The available evidence suggests that mitochondrial acetyl-CoA carboxylase represents a reservoir of enzyme which can be released and activated under lipogenic conditions.

Acute alloxan diabetes alters the activity but not the total quantity of acetyl CoA carboxylase in rat liver.

Alloxan diabetes has repeatedly been shown to reduce lipogenesis in rat liver concomitant with decreased activity of acetyl CoA carboxylase. This and other observations led to the deduction that insulin is required for the synthesis of acetyl CoA carboxylase even though the actual amount of enzyme was not measured. We have developed methods to determine the quantity of acetyl CoA carboxylase in crude tissue extracts with which we have reexamined the role of insulin in regulating the amount of the enzyme in liver of acute (3-d) alloxan diabetic rats. The results show that although there was a decrease in the quantity of the active cytoplasmic form of acetyl CoA carboxylase in the liver of alloxan diabetic rats, there was a corresponding increase in the quantity of relatively inactive forms of the enzyme associated with mitochondria. Thus, the total amount of enzyme was minimally affected by the diabetic state. Instead, the results indicate that decreased acetyl CoA carboxylase activity in liver of the diabetic rats was attributable to a shift in the subcellular distribution of the enzyme from the active cytoplasmic to inactive mitochondrial forms. We have shown previously that subcellular distribution of the enzyme is dietary dependent. Results of this study implicate insulin in the mobilization and activation of mitochondrial acetyl CoA carboxylase.

Determination of the quantity of acetyl CoA carboxylase by [14C]methyl avidin binding.

Conditions are described under which monomeric [14C]methyl avidin binds to SDS-denatured biotin enzymes and remains bound through polyacrylamide gel electrophoresis. The location of radioactive proteins on the dried gel was determined by fluorography and their identity was established by subunit molecular weight. The relative quantity of bound radioactive avidin, stoichiometrically equivalent to the molar quantity of biotin protein, can be determined by scanning the fluorograph with a soft laser densitometer. To determine the absolute quantity of biotin protein, the radioactive areas of the dried gel were cut out, resolubilized, and assayed for radioactivity. Since the specific radioactivity of the [14C]methyl avidin was known, the quantity of avidin bound and therefore the quantity of biotin enzyme could be calculated. The method is illustrated by the analysis of purified acetyl CoA carboxylase and is applied to the analysis of biotin enzymes in isolated rat liver mitochondria.

Effect of dietary 7-ketocholesterol, pure, or oxidized cholesterol on hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity, energy balance, egg cholesterol concentration, and 14C-acetate incorporation into yolk lipids of laying hens.

Experiments were conducted to study the effect of 7-ketocholesterol (7-k) in the presence or absence of pure cholesterol (PCH) or oxidized cholesterol (OCH) in diets of laying hens on reproductive performance and several parameters of cholesterol metabolism. In the first experiment, cholesterol synthesis and transport was examined by the in ovo incorporation of 14C-acetate into yolk triglycerides and cholesterol. Energy balances were also conducted. In the second experiment, hepatic 3 hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity was measured in vitro to evaluate potential cholesterol synthesis. In both experiments, reproductive performance and egg yolk cholesterol concentration were measured. Dietary PCH or OCH (.5%) significantly reduced relative acetate incorporation into yolk cholesterol, while 7-k (.025%) had no effect on carbon flow from acetate into egg cholesterol. While 7-k alone did not alter total yolk cholesterol concentration, it moderated the effect of PCH or OCH on increasing yolk cholesterol concentration. No consistent effects of dietary sterols on reproductive performance or energy balance were observed. Hepatic HMG CoA reductase activity was dramatically suppressed by feeding PCH or OCH and moderately suppressed by 7-k. In combination with PCH or OCH, 7-k did not further depress enzyme activity. The observations that 7-k alone depressed hepatic HMG-CoA reductase activity, without changing relative acetate incorporation into yolk cholesterol while limiting cholesterol deposition in egg yolk from PCH or OCH, is interpreted to mean that 7-k may stimulate sterol transport and excretion while limiting cholesterol synthesis.

Dietary dependent distribution of acetyl CoA carboxylase between cytoplasm and mitochondria of rat liver.

Biotinyl proteins in cytoplasm and mitochondria of rat liver were examined by fluorography and the quantity of acetyl CoA carboxylase was determined after sodium dodecyl sulfate-denatured proteins were incubated with [14C] methyl avidin and separated by polyacrylamide gel electrophoresis. Results show that one-half of the total acetyl CoA carboxylase in liver of fed rats was associated with mitochondria in a relatively inactive form. Fasting shifted the distribution of the enzyme toward the mitochondrial fraction and refeeding previously fasted rats shifted the distribution towards cytoplasm. Thus, acetyl CoA carboxylase can be added to the list of ambiquitous enzymes whose subcellular distribution varies with physiological conditions.