Mechanisms for the effects of fish oil lipid emulsions in the management of parenteral nutrition-associated liver disease.

Parenteral nutrition (PN) can be life saving for infants unable to adequately absorb enteral nutrients due to intestinal failure from inadequate bowel length or function. However, long-term PN carries significant morbidity and mortality, with 30 to 60% of patients developing progressive liver dysfunction. The etiology of PN-associated liver disease (PNALD) is poorly understood, however the involvement of lipid emulsions in its pathogenesis has been clearly established, with new emphasis emerging on the role of omega-6 polyunsaturated fatty acids and omega-3 polyunsaturated fatty acids. Recent studies evaluating the use of parenteral fish oil lipid emulsions instead of soybean oil lipid emulsions have demonstrated marked improvements in cholestasis, morbidity, and mortality in patients with PNALD treated with fish oil. This review provides an overview of the role of lipid emulsions in the pathogenesis of PNALD and the proposed mechanisms by which parenteral fish oil lipid emulsions may be exerting their beneficial effects.

A point mutation at the Miniature1 seed locus reduces levels of the encoded protein, but not its mRNA, in maize.

We report here on the molecular nature of an EMS-induced mutant, mn1-89, a leaky semidominant allele of the Miniature1 (Mn1) seed locus that encodes a seed-specific cell wall invertase, INCW2. The mn1-89 locus specifies normal levels of the Incw2 transcript but extremely low levels (about 6% of normal) of the protein and enzyme activity are expressed. Sequence analysis of Incw2 clones derived from the parental Mn1 and the mutant genotypes shows a C to T transition in the mn1-89 allele, leading to a single amino acid alteration (proline to leucine) near the C-terminus of the mutant INCW2 protein. Although this change is not in the catalytic domain, putative N-glycosylation sites, or the beta-fructosidase motif, it does lie in a motif that is well conserved among all plant invertases and related fructosyltransferases. On the basis of these genetic in planta data, we believe we have identified a proline residue in a hitherto unknown GPFG motif as critical for the stability of such proteins. The single base change (C to T) also leads to the elimination of a BglI restriction site in the mutant allele. Indeed, BglI restriction digests of genomic DNAs from mn1-89 and Mn1 genotypes show one and two fragments, respectively. Sequence analysis of RT-PCR-derived endosperm Incw clones from mn1-1 (the reference allele) seeds predict five amino acid substitutions relative to Mn1. Whether or not these sequences are encoded by the mn1-1 locus or another non-allelic Incw gene in the maize genome remains to be elucidated.

Measuring food insecurity and hunger in the United States: development of a national benchmark measure and prevalence estimates.

Since 1992, the U.S. Department of Agriculture Food and Nutrition Service (FNS) has led a collaborative effort to develop a comprehensive benchmark measure of the severity and prevalence of food insecurity and hunger in the United States. Based on prior research and wide consultation, a survey instrument specifically relevant to U.S. conditions was designed and tested. Through its Current Population Survey (CPS), the U.S. Bureau of the Census has fielded this instrument each year since 1995. A measurement scale was derived from the data through fitting, testing and validating a Rasch scale. The unidimensional Rasch model corresponds to the form of the phenomenon being measured, i.e., the severity of food insufficiency due to inadequate resources as directly experienced and reported in U.S. households. A categorical measure reflecting designated ranges of severity on the scale was constructed for consistent comparison of prevalence estimates over time and across population groups. The technical basis and initial results of the new measure were reported in September 1997. For the 12 months ending April 1995, an estimated 11.9% of U.S. households (35 million persons) were food insecure. Among these, 4.1% of households (with 6.9 million adults and 4.3 million children) showed a recurring pattern of hunger due to inadequate resources for one or more of their adult and/or child members sometime during the period. The new measure has been incorporated into other federal surveys and is being used by researchers throughout the U.S. and Canada.

Nutrient intakes and growth of very low birth weight infants.

OBJECTIVE: Our purpose was to determine nutrient intakes and growth of very low birth weight (VLBW) infants. STUDY DESIGN: The survey consisted of infants admitted during a 9-month period to a tertiary neonatal center. Data were obtained concerning all 51 infants born weighing <1300 gm who survived beyond 21 days of age. METHODS: At weekly intervals, intakes of fluid, energy, and protein from all sources were determined and body weight was recorded. RESULTS: During the first 2 weeks of life, intake of energy (predominantly parenteral) averaged 75 +/- 12 kcal/kg per day and intake of protein averaged 1.9 +/- 0.5 gm/kg per day. From 15 to 35 days, intake of energy (transition from parenteral to enteral) averaged 99 +/- 12 kcal/kg per day and intake of protein averaged 2.5 gm/kg per day. During the period 36 to 56 days (early enteral) and 57 days to term (late enteral), energy intakes were 108 +/- 13 and 110 +/- 15 kcal/kg per day, respectively, and protein intakes were 2.7 +/- 0.5 and 2.7 +/- 0.5 gm/kg per day, respectively. These low intakes of energy and protein (relative to presumed requirements) were explained by low intake volumes and low protein concentrations of feedings. Weight reached birth weight by 14 days of age. Subsequently, weight gains averaged 13.0, 13.8, and 11.6 gm/kg per day, respectively, in successive periods. These gains were lower than would have occurred in utero. CONCLUSION: Observed growth of VLBW infants was slow relative to in utero growth, presumably because intakes of energy and, in particular, of protein fell short of intakes needed to duplicate in utero growth. Changes in feeding practices, as well as in composition of feedings, are needed if in utero growth is to be matched.

Genetic evidence that the two isozymes of sucrose synthase present in developing maize endosperm are critical, one for cell wall integrity and the other for starch biosynthesis.

In maize, two paralogous genes, Sh1 and Sus1, encode two biochemically similar isozymes of sucrose synthase, SS1 and SS2, respectively. Previous studies have attributed the mild starch deficiency of the shrunken1 (sh1) endosperm to the loss of the SS1 isozyme in the mutant. Here we describe the first mutation in the sucrose synthase1 (Sus1) gene, sus1-1, and the isolation of a double recessive genotype, sh1 sus1-1. Combined data from diverse studies, including Northern and Western analyses, RT-PCR and genomic PCR, cloning and sequencing data for the 3' region, show that the mutant sus1-1 gene has a complex pattern of expression, albeit at much reduced levels as compared to the Sus1 gene. Endosperm sucrose synthase activity in sh1 sus1-1 was barely 0.5% of the total activity in the Sh1 Sus1 genotype. Significantly, comparative analyses of Sh1 Sus1, sh1 Sus1 and sh1 sus1-1 genotypes have, for the first time, allowed us to dissect the relative contributions of each isozyme to endosperm development. Starch contents in endosperm of the three related genotypes were 100, 78 and 53%, respectively. Anatomical analyses, which confirmed the previously described early cell degeneration phenotype unique to the sh1 Sus1 endosperm, revealed no detectable difference between the two sh1 genotypes. We conclude that the SS1 isozyme plays the dominant role in providing the substrate for cellulose biosynthesis, whereas the SS2 protein is needed mainly for generating precursors for starch biosynthesis.

Physiologic response to a protein, carbohydrate, fat meal in patients with human immunodeficiency virus who underwent small intestinal enteropathy as characterized by a kinetic model of D-xylose absorption.

PURPOSE: Small intestinal human immunodeficiency virus enteropathy is characterized by profound absorptive dysfunction unrelated to histology or pathogens. Frequently an attempt is made to compensate for this intestinal failure by supplementing nutrient intake with nourishing liquid meals. It is not known how the diminished absorptive function in these patients will respond to this intake. With the use of a D-xylose kinetic model of absorption, we determined the absorptive response of patients with small intestinal enteropathy to an isotonic liquid feeding. METHODS: Seven male patients with acquired immunodeficiency syndrome (AIDS), diarrhea, weight loss, and no detectable pathogens (stool studies and duodenal biopsy) were enrolled. After an overnight fast, the patients were studied on three separate days. On day 1, the patients received 15 g oral D-xylose. On day 2, 10 g i.v. D-xylose was given. On day 3, 15 g oral D-xylose was again given along with 250 mL of a liquid polymeric isotonic diet. Serum and urine collections were obtained to calculate the kinetic rate constants and extent of D-xylose absorption. RESULTS: Mean values for the rate constant for absorption of D-xylose, Ka, (0.26/h; N > 0.65) and the rate constant for nonabsorptive loss, K0' (2.47/h; N < 0.353) were very abnormal before the meal. Mean K0 improved (decreased to 0.66), but Ka and bioavailability, F, did not have a statistically significant change after the meal. The improvement in mean K0 with the meal was much more pronounced in the five subjects with high K0 values before the meal (without meal 3.22: with meal 0.67; p < .05). CONCLUSIONS: (1) An isotonic liquid polymeric diet leads to less nonabsorptive loss of D-xylose, but does not affect the extent of D-xylose absorption in this group as a whole. This is probably due to the meal slowing gastric emptying. (2) Improvement in nonabsorptive loss with a meal is most pronounced when there is excessive nonabsorptive loss, K0, without a meal. (3) Improvement in nonabsorptive losses with a meal might predict which patients will benefit from antimotility agents and continued feedings vs those requiring i.v. hyperalimentation.

Cloning of a novel maize endosperm-specific protein with partial sequence homology to a pollen surface protein.

A gene encoding a novel maize endosperm protein has been cloned and sequenced. The gene encodes a 43 135 Da polypeptide which is 42% identical over two segments of an alfalfa pollen protein sequence. The gene is expressed in developing endosperm tissue, and not in other tissues such as shoot, pollen, or embryo.

Erythrocyte incorporation and absorption of 58Fe in premature infants treated with erythropoietin.

We hypothesized that treatment of very low birth weight premature infants with r-HuEPO would increase erythrocyte incorporation and gastrointestinal absorption of iron. Infants with birth weights < or = 1.25 kg and gestational ages < 31 wk were randomized to receive 6 wk of 500 U of r-HuEPO/kg/wk (epo group, n = 7) or placebo (placebo group, n = 7). All infants received daily enteral supplementation with 6 mg of elemental iron per kg. An enteral test dose of a stable iron isotope, 58Fe, was administered after the 1st ("early dosing") and 4th ("late dosing") wk of treatment. Mean (+/-SD) erythrocyte incorporation of the dose of 58Fe administered determined 2 wk after early dosing was significantly greater in the epo group compared with the placebo group (4.4% +/- 1.6 versus 2.0 +/- 1.4%, p = 0.013). In contrast, after late 58Fe dosing, there was no difference between groups in incorporation (3.8 +/- 1.6% versus 5.5 +/- 2.7%). Within the epo group, percentage erythrocyte incorporation of 58Fe did not differ between early and late dosing, whereas in the placebo group it increased 3-fold (p < 0.01). Percentage absorption of 58Fe was not different between the epo and placebo groups after both early dosing (30 +/- 22% versus 34 +/- 8%) and late dosing (32 +/- 9% versus 31 +/- 6%). Absorption of nonlabeled elemental iron and 58Fe were significantly correlated with one another. The percentage of the absorbed 58Fe dose incorporated into Hb was not different between groups. We conclude that, although erythropoietin treatment stimulates erythrocyte iron incorporation in premature infants, it has no effect on iron absorption at the r-HuEPO dose studied.

Urinary recovery of lactulose compared to D-xylose absorption kinetics in HIV patients with diarrhea and weight loss.

Using a kinetic model of D-xylose absorption, we have previously shown that there is severely impaired absorption of D-xylose in HIV patients with diarrhea and weight loss. The absorptive defect is characterized by an increased rate constant for nonabsorptive loss of D-xylose, Ko, and a decreased absorptive rate constant, Ka, and is unrelated to histology or the presence of pathogens. It is not known if there is also abnormal paracellular transport in these patients. We have extended our observations in these patients by including a measurement of paracellular transport, lactulose absorption. Nine HIV patients with chronic diarrhea, weight loss, and no detectable intestinal pathogens, two healthy volunteers, and three non-HIV patients with chronic diarrhea (two functional and one with scleroderma) were enrolled. Of the nine HIV patients, six had diminished bioavailability of D-xylose, F (range: 19-52%, normal >70%), and elevated rate constant for nonabsorptive loss, Ko (range: 0.54-1.35/hr, normal <0.353/min). Four of the six also had decreased Ka (range: 0.09-0.36/hr, normal >0.634/min). Only one of these six had increased lactulose recovery (3.51%, normal <0.5%). Two of three patients with normal kinetic parameters of D-xylose absorption had increased lactulose urinary recovery (1.92%, 2.61%). In conclusion, lactulose absorption is increased in some patients with HIV-related diarrhea who have normal D-xylose absorption, suggesting a paracellular mechanism for diarrhea in some patients with AIDS enteropathy.

Evidence for plasma membrane-associated forms of sucrose synthase in maize.

Plasma membrane fractions were isolated from maize (Zea mays L.) endosperms and etiolated kernels to investigate the possible membrane location of the sucrose synthase (SS) protein. Endosperms from seedlings at both 12 and 21 days after pollination (DAP), representing early and mid-developmental stages, were used, in addition to etiolated leaf and elongation zones from seedlings. Plasma membrane fractions were isolated from this material using differential centrifugation and aqueous two-phase partitioning. The plasma membrane-enriched fraction obtained was then analyzed for the presence of sucrose synthase using protein blots and activity measurements. Both isozymes SS1 and SS2, encoded by the loci Sh1 and Sus1, respectively, were detected in the plasma membrane-enriched fraction using polyclonal and monoclonal antisera to SS1 and SS2 isozymes. In addition, measurements of sucrose synthase activity in plasma membrane fractions of endosperm revealed high levels of specific activity. The sucrose synthase enzyme is tightly associated with the membrane, as shown by Triton X-100 treatment of the plasma membrane-enriched fraction. It is noteworthy that the gene products of both Sh1 and Sus1 were detectable as both soluble and plasma membrane-associated forms.

Progression of gastritis to monoclonal B-cell lymphoma with resolution and recurrence following eradication of Helicobacter pylori.

OBJECTIVE: To follow a patient with Helicobacter pylori-associated gastritis by performing serial endoscopic biopsies to observe the histologic progression of the gastritis to a monoclonal B-cell lymphoma with resolution and subsequent recurrence following eradication of H pylori organisms. DESIGN: A case report of a patient followed over 3 years. MAIN OUTCOME MEASURES: Characteristics of the gastric mucosa as determined by histologic and gene rearrangement studies on multiple random biopsies obtained serially before and after the eradication of H pylori organisms. RESULTS: A progression from H pylori-associated gastritis through lymphoid hyperplasia to a monoclonal B-cell lymphoma was observed. With the techniques used, a resolution of the lymphoma was observed on eradication of H pylori organisms, with a subsequent recurrence of the lymphoma 15 months later, despite the absence of H pylori organisms. CONCLUSION: The observations made of this patient support an association between H pylori and the development of a gastric monoclonal B-cell lymphoma. This lesion appears to develop in the setting of gastritis and progresses through lymphoid hyperplasia followed subsequently by the lymphoma. We speculate that this process is initially antigen driven by the organism and may subsequently become autonomous as genetic damage is accumulated, so that eradication of H pylori organisms will lead to regression of the lesion to the degree that there are autonomously proliferating cells present.

Malabsorption and deficiency of vitamin B12 in HIV-infected patients with chronic diarrhea.

Deficiency of vitamin B12 is commonly reported in HIV-infected patients. We measured vitamin B12 levels in 36 HIV-infected patients with chronic diarrhea (> 3 stools/day for six weeks or more). Eight patients had an identifiable cause of diarrhea. Vitamin B12 levels were low in 39%. Sixteen of these patients were selected to undergo further testing, eight patients with low levels of vitamin B12 and eight with normal B12 levels. These 16 patients had both a stage II Schilling test and measurement of multiple serum D-xylose concentrations performed after both oral and intravenous doses of D-xylose. Integrated areas under the curves (AUC) for D-xylose concentration versus time were calculated for intravenous and oral doses, and D-xylose bioavailability was determined. Stage II Schilling tests were abnormal in 11 patients, (69%). D-Xylose bioavailability correlated closely with vitamin B12 absorption (r = 0.648, P < 0.01). Comparisons of mean values for CD4 count, serum albumin, Karnovsky score, six-month weight loss, 1-hr serum D-xylose levels and MCV failed to reveal a significant difference between those with and without abnormal serum vitamin B12 levels. These data indicate that below-normal levels of vitamin B12 are highly prevalent in HIV-infected patients with chronic diarrhea. Malabsorption of vitamin B12 occurs in the setting of an enteropathic process effecting both the proximal and distal small bowel. Since no risk factors for vitamin B12 deficiency could be identified, screening for vitamin B12 deficiency in HIV-infected patients with chronic diarrhea is strongly recommended.

Carbonic Anhydrase Activity in Isolated Chloroplasts of Wild-Type and High-CO2-Dependent Mutants of Chlamydomonas reinhardtii as Studied by a New Assay.

In an assay of carbonic anhydrase (CA), NAH14CO3 soltution at the bottom of a sealed vessel releases 14CO2, which diffuses to the top of the vessel to be assimilated by photosynthesizing Chlamydomonas reinhardtii cells that have been adapted to a low-CO2 environment. The assay is initiated by illuminating the cells and is stopped by turning the light off and killing the cells with acid. Enzyme activity was estimated from acid-stable radioactivity. With bovine CA, 1.5 Wilbur-Anderson units (WAU) was consistently measured at 5- to 6-fold above background. Sonicated whole cells of air-adapted wild-type C. reinhardtii had 740 [plus or minus] 12.4 WAU/mg chlorophyll (Chl). Sonicated chloroplasts from a mixotrophically grown wall-less strain, cw-15, had 35.5 [plus or minus] 2.6 WAU/mg Chl, whereas chloroplasts from wall-less external CA mutant strain cia5/cw-15 had 33.8 [plus or minus] 1.9 WAU/mg Chl. Sonicated chloroplasts from the wall-less mutant strain cia-3/cw-15, believed to lack an internal CA, had 2.8 [plus or minus] 3.2 WAU/mg Chl. Sonicated whole cells from cia3/cw-15 had 2.8 [plus or minus] 7.8 WAU/mg Chl. Acetazolamide, ethoxyzolamide, and p-aminomethylbenzene sulfonamide (Mafenide) at 100 [mu]M inhibited CA in sonicated chloroplasts from cia-5/cw-15. Treatment at 80[deg]C for 10 min inhibited this CA activity by 90.8 [plus or minus] 3.6%. Thus, a sensitive 14C assay has confirmed the presence of a CA in cw-15 and cia-5/cw-15 chloroplasts and the lack of a CA in cia-3/cw-15 chloroplasts. Our results indicate that HCO3- is the inorganic carbon species that is accumulated by chloroplasts of Chlamydomonas and that chloroplastic CA is responsible for the majority of internal CA activity.

Nutritional management of infants with bronchopulmonary dysplasia.

The nutritional needs of the child with bronchopulmonary dysplasia (BPD) vary significantly from those of a healthy child. To address the many special aspects of the nutritional care of the child with BPD, a nutrition management protocol was established at the University of Iowa Hospitals and Clinics. This protocol discusses caloric requirements; selection of enteral feedings; electrolyte, vitamin, and mineral supplements; growth, oral feeding advancement, and monitoring of nutritional status. Although many of the guidelines are supported by research, some are based on clinical practice. Many questions remain to be answered about the optimal nutrition therapy for these infants. One goal of this protocol is to stimulate discussion and research that will lead to a better understanding of the nutritional requirements of the BPD population.

Reproducibility and accuracy of angle measurements obtained under static conditions with the Motion Analysis video system.

The development of computerized and semi-automated motion analysis systems has made the study of human motion more widely available in research and clinical settings. Although many of these systems are currently used by physical therapists, the accuracy and reproducibility of some of these systems in estimating joint angles have not been reported. In this study, the accuracy and reproducibility of angle measurements obtained by use of the Motion Analysis video system were evaluated under static conditions using a standard goniometer. Reflective markers placed on a goniometer were recorded by two video cameras at 17 angles, from 20 to 180 degrees, in 10-degree increments. Recordings of the goniometer were made at three locations within the field of view of the cameras. The intraclass correlation coefficient for each location tested was .99. Average within-trial variability was less than 0.4 degree at all locations. A linear regression of the system-calculated angles and reference angles for all locations had slopes near unity (ie, 1) and intercepts that were not statistically different from zero. A preliminary evaluation of the system under dynamic conditions revealed that distances were slightly underestimated, regardless of where the movement occurred within the calibration cube.

Effect of a lactase preparation on lactose content and osmolality of preterm and term infant formulas.

Lactose intolerance due to lactase deficiency often follows acute gastroenteritis. In such situations, a lactose-free formula may be indicated for preterm infants. Therefore, the effect of addition of lactase on the lactose content and osmolality of preterm and term infant formulas was studied. Lactose content of formulas at room temperature was decreased by approximately 50% 1 hour after addition of lactase. Concentration of lactose was reduced by 70% or more after 2 hours in all formulas. Because of the higher initial lactose concentration in term formulas, it took 24 hours to reach the same absolute lactose concentration (10 g/kg formula) found in preterm formulas after 2 hours. There was a moderate increase in osmolality in preterm formulas. The increase was greater in term formulas because of the greater initial concentration of lactose. The addition of lactase appears to be a suitable method for reduction of lactose content of preterm and term formulas, although the increase in osmolality of term formulas may preclude their clinical use.

The enamel ultrastructure of multituberculate mammals: a review.

The enamel ultrastructure of multituberculate mammals has been sampled extensively and studied intensively and is better known than for any other group of early mammals. The enamel of the earliest multituberculates, those of the Late Triassic-Early Jurassic suborder Haramiyoidea and the Late Jurassic-early Early Cretaceous suborder Plagiaulacoidea, is "preprismatic." With only two exceptions, all Late Cretaceous and early Tertiary genera of multituberculates examined have prismatic enamel. Prisms are either small with circular (complete) boundaries or large with arc-shaped (incomplete) boundaries. There is a remarkably consistent relationship between enamel ultrastructural type and subordinal taxa in that small, circular prisms are usually found within the suborder Ptilodontoidea and large, arc-shaped prisms are usually found in the suborder Taeniolabidoidea and in six Late Cretaceous-Early Tertiary genera of indeterminate subordinal status. Research currently in progress suggests that both small, circular prisms and large, arc-shaped prisms are homologous in all multituberculates in which they occur, with one exception. Neoliotomus, a taeniolabidoid, appears to have evolved small, circular prisms independently. In addition, it appears that large, arc-shaped prisms represent the primitive condition in multituberculates with prismatic enamel, not small, circular prisms as has been proposed previously.

A critical review of periodic health screening using specific screening criteria. Part 4: selected miscellaneous diseases.

Despite the increasing interest in recent years in prevention and early recognition of asymptomatic disease, an objectively based program for periodic health screening of asymptomatic adults has yet to be proposed for the primary care physician. This is the last in a series of four articles which have critically examined the feasibility of screening procedures for 36 selected diseases. Six basic criteria are adopted as necessary to justify periodic screening. Specific screening recommendations are made for each disease, and a longitudinal screening program for asymptomatic adults is proposed. Cost and patient education are two important factors in any viable screening program.

A critical review of periodic health screening using specific screening criteria. 3. Selected diseases of the genitourinary system.

Despite the increasing interest in recent years in prevention and early recognition of asymptomatic disease, an objectively based program for periodic health screening of asymptomatic adults has yet to be proposed for the primary care physician. This is the third in a series of four articles which will critically examine the feasibility of screening procedures for 36 selected diseases. Six basic criteria are adopted as necessary to justify periodic screening. Specific screening recommendations are made for each disease, and a longitudinal screening program for asymptomatic adults will be proposed in the concluding article of this series.