Effect of Calcium Derived from Lithothamnion sp. on Markers of Calcium Metabolism in Premenopausal Women.

A double-blind crossover pilot trial tested the hypothesis that botanically derived calcium could demonstrate greater influence over calcium metabolism markers compared with a nonplant-derived calcium carbonate supplement or placebo. Twelve fasting female subjects received a single oral dose of Aquamin F™ (derived from the marine algal Lithothamnion sp.), or calcium carbonate, or placebo.

GRAS from the ground up: Review of the Interim Pilot Program for GRAS notification.

After publication of the draft Generally Regarded As Safe (GRAS) rule in 1997, the United States (US) Food and Drug Administration (FDA) initiated an Interim Pilot Program encouraging the notification to FDA of GRAS determinations. This paper analyzes GRAS notifications submitted during the Interim Pilot Program along with warning letters issued during the same time period to better understand the evolution of the program and anticipate the future GRAS landscape. The success of the GRAS Notification program is demonstrated by the increasing rate of GRAS Notifications submitted to the FDA during the Interim Pilot Program, as well as the shift from a primarily domestic process to a process featuring an equal to greater contribution of GRAS Notifications from companies outside the US.

Meal Replacement Beverage Twice a Day in Overweight and Obese Adults (MDRC2012-001).

This open label, single arm, prospective, interventional, weight loss trial evaluated a meal replacement beverage (Right Size(®) Smoothie) used to replace breakfast and lunch each day for 12 weeks (7 clinic visits) as part of a calorie-restricted diet in overweight and obese adults. A total of 155 individuals were screened, 55 enrolled and 28 completed this 12 week study. Subjects were obese (mean weight: 206 pounds and BMI: 32.

Reduced viscosity Barley β-Glucan versus placebo: a randomized controlled trial of the effects on insulin sensitivity for individuals at risk for diabetes mellitus.

Background: Prior studies suggest soluble fibers may favorably affect glucose/insulin metabolism.

Methods: This prospective, randomized, placebo controlled, double blind, parallel group trial evaluated 50 generally healthy subjects without prior diagnosis of diabetes mellitus (44 completers), who were administered beverages containing placebo (control), lower dose (3 g/d), or higher dose (6 g/d) reduced viscosity barley β-glucan (BBG) extract. Subjects (68% women) mean age 56 years, Body Mass Index (BMI) 32 kg/m2 and baseline fasting plasma glucose 102 mg/dl were instructed to follow a weight-maintaining Therapeutic Lifestyle Changes (TLC) diet and consumed three 11 oz study beverages daily with meals for 12 weeks.

A novel liquid multi-phytonutrient supplement demonstrates DNA-protective effects.

This study explored the DNA protective (anti-mutagenic) effects of an oral, liquid, multi-phytonutrient dietary supplement containing a proprietary blend of fruits, vegetables and aloe vera concentrated components in addition to a proprietary catechin complex from green tea (VIBE Cardiac & Life, Eniva Nutraceuticals, Anoka, MN; herein described as "VIBE"). This study tested the hypothesis that VIBE would reduce DNA damage in skin cells exposed to UVR. Human epidermal cells, from the cell line A431NS, were treated with 0% (control), 0.

A natural seaweed derived mineral supplement (Aquamin F) for knee osteoarthritis: a randomised, placebo controlled pilot study.

Background: Osteoarthritis (OA) is a slowly destructive process that may be influenced by a nutritional mineral balance in the body.

Methods: This small, double blind, placebo controlled pilot study investigated the impact of treatment with a natural multi-mineral supplement from seaweed (Aquamin) on 6 minute walking distance (6 MWD), range of motion (ROM), and pain and joint mobility measured by the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index in subjects with moderate to severe OA of the knee during gradual withdrawal of non-steroidal anti-inflammatory drugs (NSAIDs) that were being used daily for pain management. Subjects (n = 29) with moderate to severe OA of the knee were randomised to receive either Aquamin (2400 mg/d) or Placebo for up to 12 weeks.

A whey-protein supplement increases fat loss and spares lean muscle in obese subjects: a randomized human clinical study.

Background: This study evaluated a specialized whey fraction (Prolibratrade mark, high in leucine, bioactive peptides and milk calcium) for use as a dietary supplement to enhance weight loss.

Methods: This was a randomized, double-blind, parallel-arm, 12-week study. Caloric intake was reduced 500 calories per day.

A natural mineral supplement provides relief from knee osteoarthritis symptoms: a randomized controlled pilot trial.

Background: This small, pilot study evaluated the impact of treatment with a natural multi-mineral supplement from seaweed (Aquamin) on walking distance, pain and joint mobility in subjects with moderate to severe osteoarthritis of the knee.

Methods: Subjects (n = 70) with moderate to severe osteoarthritis of the knee were randomized to four double-blinded treatments for 12 weeks: (a) Glucosamine sulfate (1500 mg/d); (b) Aquamin (2400 mg/d); (c) Combined treatment composed of Glucosamine sulfate (1500 mg/d) plus Aquamin (2400 mg/d) and (d) Placebo. Primary outcome measures were WOMAC scores and 6 Minute Walking Distances (6 MWD).

HUM5007, a novel combination of thermogenic compounds, and 3-acetyl-7-oxo-dehydroepiandrosterone: each increases the resting metabolic rate of overweight adults.

This study tested the hypothesis that 3-acetyl-7-oxo-dehydroepiandrosterone alone (7-Keto) and in combination with calcium citrate, green tea extract, ascorbic acid, chromium nicotinate and cholecalciferol (HUM5007) will increase the resting metabolic rate (RMR) of overweight subjects maintained on a calorie-restricted diet. In this randomized, double-blind, placebo-controlled, crossover trial, overweight adults on a calorie-restricted diet were randomized to three 7-day treatment periods with 7-Keto, HUM5007 or placebo. Resting metabolic rate was measured by indirect calorimetry at the beginning and end of each treatment period with a 7-day washout between testing periods.

AF4 encodes a ubiquitous protein that in both native and MLL-AF4 fusion types localizes to subnuclear compartments.

Acute leukemia with t(4;11)(q21,q23) translocation results from the in-frame fusion of the MLL to the AF4/FEL gene. In previous studies, we and others demonstrated that AF4 transcripts are present in a variety of hematopoietic and nonhematopoietic human cells. To further study the wild-type and leukemia fusion AF4, we used glutathione S-transferase (GST)-fusion proteins as immunogens to produce rabbit polyclonal antibodies that were specific for normal and chimeric AF4 proteins.

MLL gene rearrangement, cytogenetic 11q23 abnormalities, and expression of the NG2 molecule in infant acute myeloid leukemia.

To study prognostic factors in infant acute myeloid leukemia (AML), we analyzed 44 children treated on Childrens Cancer Group protocols for MLL gene rearrangement by Southern blot, cytogenetic 11q23 abnormalities, and reactivity with monoclonal antibody 7.1. This antibody detects the human homologue of the rat NG2 chondroitin sulfate proteoglycan molecule, which has previously been reported to be expressed on human melanoma.

Molecular analysis of infant acute leukemia.

Infant acute leukemia, known to have a poor outcome with conventional therapy, usually has a molecular rearrangement at chromosome band 11q23. The 11q23 translocation partner is typically at 4q21 in infant ALL, but other 11q23 translocation partners occur in infant ALL and AML. The MLL gene at 11q23, and the AF4 gene at 4q21, have been extensively studied to identify heterogeneity of structural rearrangement and prognostic indicators, to look for clues as to etiology, and to improve therapy.

AF4/FEL, a gene involved in infant leukemia: sequence variations, gene structure, and possible homology with a genomic sequence on 5q31.

The most common chromosome abnormality among infants with acute lymphoblastic leukemia is a t(4;11)(q2l;q23) and patients with this 4;11 translocation have a very poor prognosis. This unique genetic rearrangement fuses the MLL/ALL-1/HRX-Htrx gene at 11q23 with the AF4/FEL gene at 4q21. The resulting chimeric mRNAs presumably encode chimeric proteins which contribute to the leukemogenic state.

Rearrangement of the MLL gene confers a poor prognosis in childhood acute lymphoblastic leukemia, regardless of presenting age.

MLL gene rearrangements are associated with an extremely poor prognosis in infants with acute lymphoblastic leukemia (ALL), but little is known about their clinical significance in older children. Therefore, we studied 45 cases of childhood ALL with abnormalities of chromosome 11q23 for rearrangement of the MLL gene to determine if this feature confers a uniformly poor prognosis. MLL gene rearrangements were detected in all 18 cases with the common t(4;11), t(9;11) or t(11;19) translocations, whereas only 5 of 12 patients with either unbalanced or uncommon balanced translocations demonstrated a rearrangement.

Differential expression of AF4/FEL mRNA in human tissues.

This manuscript reports the differential expression of the AF4 gene among human tissues. AF4 mRNA is highly expressed in normal placental tissue which correlates with the newborn age of patients presenting with leukemia characterized by the MLL/AF4 gene rearrangement.

Molecular analysis of infant acute lymphoblastic leukemia: MLL gene rearrangement and reverse transcriptase-polymerase chain reaction for t(4; 11)(q21; q23).

Molecular techniques to detect MLL (11q23) and AF-4 (4q21) gene rearrangements are being evaluated for use in stratification of patients into prognostic groups. We studied 15 cases of infant acute lymphoblastic leukemia (ALL) with Southern blotting for MLL gene rearrangement and reverse transcriptase-polymerase chain reaction (RT-PCR) for t(4;11) fusion transcripts and compared the results to cytogenetic and clinical data. Our results indicate that classic t(4;11)(q21;q23) translocations are detected by RT-PCR; however, unusual 4;11 translocations still require additional investigation.

Acute lymphoblastic leukemias with deletion of 11q23 or a novel inversion (11)(p13q23) lack MLL gene rearrangements and have favorable clinical features.

Balanced translocations affecting the 11q23 region are among the most frequent chromosomal abnormalities in childhood acute lymphoblastic leukemia (ALL), comprising 5% to 6%. These cases consistently have a rearranged MLL gene and are associated with high-risk presenting features, hyperleukocytosis and younger age, and a poor treatment outcome. To assess the clinical and biologic significance of 11q23-associated structural chromosomal abnormalities other than translocations, we studied 17 cases of childhood ALL [14 with del(11)(q23) and 3 with inv(11)(p12q23)] that were identified among 785 cases with successful chromosome analysis.

Heterogeneity in MLL/AF-4 fusion messenger RNA detected by the polymerase chain reaction in t(4;11) acute leukemia.

We have designed a single polymerase chain reaction (PCR) primer pair that detects the MLL/AF-4 fusion mRNA encoded by the derivative 11 chromosome from t(4;11)(q21;q23) leukemia cells using the reverse transcriptase PCR technique. PCR amplification was possible in seven of seven cells studied. Sequencing of the amplified products showed three different breakpoints on 11q23 and three on 4q21, resulting in six unique fusion sequences.

The chromosome 4q21 gene (AF-4/FEL) is widely expressed in normal tissues and shows breakpoint diversity in t(4;11)(q21;q23) acute leukemia.

The chromosomal translocation, t(4;11)(q21;q23), is the most common type of 11q23 chromosomal abnormality, being highly prevalent in infant acute leukemias and associated with a poor prognosis. The t(4;11) results in the fusion of an 11q23 gene (MLL, HRX, Htrx-1, or ALL-1) and a 4q21 gene (AF-4 or FEL). To further evaluate the 4q21 gene and its role in t(4;11) acute leukemia, we have cloned a 38-kb genomic region and mapped exons of the AF-4 gene.

Cell-surface expression of immunoglobulin G receptors on the polymorphonuclear leukocytes and monocytes of extremely premature infants.

This study measured Fc gamma receptor (FcR) expression on polymorphonuclear leukocytes (PMN) and monocytes from extremely premature infants. Flow cytometry was used to quantitate FcRIII [cluster of differention (CD) 16], FcRII (CD32), FcRI (CD64), CD14, and CD67 proteins on the PMN surface. Sixty-four premature infants with a mean gestational age +/- SD of 26 +/- 2 wk (birth weight = 847 +/- 217 g), 12 infants born at term (gestational age = 38 +/- 1 wk), and 37 adults were studied.

Recurring chromosome abnormalities in Hodgkin's disease.

Cytogenetic analysis was performed on lymph nodes or other tumor masses from 33 patients with Hodgkin's disease. Metaphase cells were obtained in 25 of the 33 cases. Analyzable abnormal clones were found in nine cases.