Biomedical subjects

P Zhang

Publications and source records attributed to P Zhang.

At least 73 records · Page 4Linked to original sources

PubMed2001

A novel PCNA-binding motif identified by the panning of a random peptide display library.

Proliferating cell nuclear antigen (PCNA) has recently been identified as a target for the binding of proteins involved in DNA replication, DNA repair, and cell cycle control. The interactions between PCNA and a number of these proteins are known to be mediated by a conserved peptide motif. In this study, a random peptide library in which peptide sequences are displayed on the E. coli bacterial flagellin protein was screened for PCNA-binding sequences. Analysis of the retrieved peptide sequences verified the presence of the known PCNA-binding motif. In addition, a second, larger group of peptides containing a different consensus sequence for PCNA binding was discovered. This sequence was found to be present on DNA polymerase delta, and a peptide conforming to this sequence was demonstrated to bind to PCNA. Database search and analysis show that many proteins contain the second consensus sequence. These include proteins that are involved in DNA replication, repair, and cell cycle control. The demonstration of this second PCNA-binding motif may provide a basis for identifying and experimentally testing specific proteins for the structural basis for PCNA binding.

Amino Acid Motifs↗

PubMed2001

[Association between estrogen receptor gene polymorphisms and acute myocardial infraction].

OBJECTIVE: To study the distribution of estrogen receptor (ER) in Chinese Hans population and the association of ER gene polymorphisms with acute myocardial infarction (AMI). METHODS: ER genotyping was performed in 75 AMI patients and 118 controls by PCR-RFLP. The serum lipid levels of the subjects were also determined. 46 AMI patients were examined by selected coronary angiography (SCA). RESULTS: ER allelic frequencies of X, x and P, p alleles were 0.207, 0.793; 0.169, 0.831 and 0.287, 0.713; 0.399, 0.661 in AMI and control groups respectively. There was no significant difference between the distribution of Xbal and PvaII polymorphisms in AMI group and control group (P > 0.05). The serum lipid levels and the results of SCA were also not significantly difference among genotypes in intra-group. But the distributions of PvuII genotypes were significantly different between AMI group and controls (P < 0.05). CONCLUSION: XbaI polymorphisms are not related to AMI. But PvuII polymorphisms are associated with AMI, they might be a risk factor for AMI.

Adult↗

PubMed2001

Behavior of integrate-and-fire and Hodgkin-Huxley models with correlated inputs.

We assess, both numerically and theoretically, how positively correlated Poisson inputs affect the output of the integrate-and-fire and Hodgkin-Huxley models. For the integrate-and-fire model the variability of efferent spike trains is an increasing function of input correlation, and of the ratio between inhibitory and excitatory inputs. Interestingly for the Hodgkin-Huxley model the variability of efferent spike trains is a decreasing function of input correlation, and for fixed input correlation it is almost independent of the ratio between inhibitory and excitatory inputs. In terms of the signal to noise ratio of efferent spike trains the integrate-and-fire model works better in an environment of asynchronous inputs, but the Hodgkin-Huxley model has an advantage for more synchronous (correlated) inputs. In conclusion the integrate-and-fire and Hodgkin-Huxley models respond to correlated inputs in totally opposite ways.

Action Potentials↗

PubMed2001

Nucleotide sequence, transcription map, and mutation analysis of the 13q14 chromosomal region deleted in B-cell chronic lymphocytic leukemia.

Deletions of the 13q14 chromosome region are associated with B-cell chronic lymphocytic leukemia (B-CLL) and several other types of cancer, suggesting the presence of a tumor suppressor gene. In previous studies the minimal region of deletion (MDR) was mapped to a less than 300-kilobase (kb) interval bordered by the markers 173a12-82 and 138G4/1.3R. For the identification of the putative tumor suppressor gene, the entire MDR (approximately 347 kb) has been sequenced, and transcribed regions have been identified by exon trapping, EST-based full-length complementary DNA cloning, database homology searches, and computer-assisted gene prediction analyses. The MDR contains 2 pseudogenes and 3 transcribed genes: CAR, encoding a putative RING-finger containing protein; 1B4/Leu2, generating noncoding transcripts; and EST70/Leu1, probably representing another noncoding gene (longest open reading frame of 78 codons). These genes have been sequenced in 20 B-CLL cases with 13q14 hemizygous deletion, and no mutations were found. Moreover, no somatic variants were found in the entire MDR analyzed for nucleotide substitutions by a combination of direct sequencing and fluorescence-assisted mismatch analysis in 5 B-CLL cases displaying 13q14-monoallelic deletion. The nondeleted allele of the CAR and EST70/Leu1 genes was expressed in B-CLL specimens, including those with monoallelic loss, whereas no expression of 1B4/Leu2 was detectable in B-CLL, regardless of the 13q14 status. These results indicate that allelic loss and mutation of a gene within the MDR is an unlikely pathogenetic mechanism for B-CLL. However, haplo-insufficiency of one of the identified genes may contribute to tumorigenesis. (Blood. 2001;97:2098-2104)

Animals↗

PubMed2001

The amino-terminal heptad repeats of the coiled-coil neck domain of pulmonary surfactant protein d are necessary for the assembly of trimeric subunits and dodecamers.

Pulmonary surfactant protein D (SP-D), a lung host defense protein, is assembled as multimers of trimeric subunits. Trimerization of SP-D monomers is required for high affinity saccharide binding, and the oligomerization of trimers is required for many of its functions. A peptide containing the alpha-helical neck region can spontaneously trimerize in vitro. However, it is not known whether this sequence is necessary for the complete cellular assembly of disulfide-cross-linked, trimeric subunits and dodecamers. For the present studies, we synthesized mutant cDNAs with deletions or site-directed substitutions in the neck domain of rat SP-D, and examined the assembly of the newly synthesized proteins after transfection of CHO-K1 cells. The neck domain contains three "classical" heptad repeat motifs with leucine residues at the "d position," and a distinctive C-terminal repeat previously suggested to drive trimeric chain association. Deletion of the highly conserved core of the latter repeat (FSRYLKK) did not interfere with the secretion of dodecamers with lectin activity. By contrast, deletion of the entire neck domain or deletion of one or two amino-terminal repeats resulted in defective molecular assembly. The secreted proteins eluted in the position of monomers by gel filtration under nondenaturing conditions. In addition, the neck + carbohydrate recognition domain of SP-D was necessary and sufficient for the trimerization of a heterologous collagen sequence located amino-terminal to the trimeric coiled-coil. These studies provide strong evidence that the amino-terminal heptad repeats of the neck domain are necessary for the intracellular, trimeric association of SP-D monomers and for the assembly and secretion of functional dodecamers.

Amino Acid Sequence↗

PubMed2001

Mouse phosphoglycerate mutase M and B isozymes: cDNA cloning, enzyme activity assay and mapping.

Two mouse cDNAs encoding the non-muscle-specific or brain isoform (type B, Pgam1) and the muscle-specific isoform (type M, Pgam2) of phosphoglycerate mutase (PGAM) were isolated and characterized. Pgam1 contains a 765 bp open reading frame (ORF) coding for a 254-residue protein while Pgam2 contains a 762 bp ORF coding for a 253-residue protein. The deduced proteins of mouse Pgam1 and Pgam2 are highly similar to those of human and rat (> or = 93% similarity). Northern blot analysis showed that the expression patterns of Pgam1 and Pgam2 were distinct. Pgam1 was expressed as a 2.1-kb transcript highly in brain and kidney and moderately in liver, thyroid, stomach and heart, whereas Pgam2 was expressed as a 1.0-kb transcript highly in muscle, testis and moderately in heart and lung, but was not detectable in the other six tissues examined. Transfecting the cDNA fragments containing the entire ORFs of these two cDNAs into COS7 cells for transient expression, respectively, the enzyme activities of mouse Pgam1 and Pgam2 were detected to be 2.2-2.5 times of those of COS7 cells and COS7 cells transfected with vector, proving the validity of mouse Pgam1 and Pgam2 cDNAs we report here. Pgam1 and Pgam2 were assigned to 116.16 cR from D19Mit52 and 29.57 cR from D11Mit129, respectively, by radiation hybrid method. The partial genomic sequence of Pgam2 was determined, which showed that mouse Pgam2 consisted at least three exons and two introns. In addition, a pseudogene of Pgam1, Pgam1-ps1, was identified from mouse genomic sequence.

Amino Acid Sequence↗

PubMed2001

Conformations of nucleoside analogue 1-(2'-deoxy-beta-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide in different DNA sequence contexts.

The concept of using a dynamic base-pairing nucleobase as a mode for degenerate recognition presents a unique challenge to analysis of DNA structure. Proton and phosphorus NMR studies are reported for two nine-residue DNA oligodeoxyribonucleotides, d(CATGGGTAC).d(GTACNCATG) (1) and d(CATGTGTAC).(GTACNCATG) (2), which contained 1-(2'-deoxy-beta-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide (N) in the center of the helix at position 14. The duplexes were compared to the canonical Watson-Crick duplexes, d(CATGGGTAC).d(GTACCCATG) (3) and d(CATGTGTAC).d(GTACACATG) (4). Two-dimensional NOESY spectra of 1-4 in H(2)O and D(2)O solutions collected at 5 degrees C allowed assignment of the exchangeable and nonexchangeable protons for all four oligodeoxyribonucleotides. Thermodynamic and circular dichroism data indicated that 1-4 formed stable, B-form duplexes at 5 degrees C. Two-dimensional (1)H-(31)P correlation spectra indicated that there were minor perturbations in the backbone only near the site of the triazole base. Strong NOESY cross-peaks were observed between the H5 and H1' of N14 in 1 and, unexpectedly, 2, which indicated that, in both duplexes, N14 was in the syn(chi)() conformation about the glycosidic bond. NOESY spectra of 1 and 2 recorded in 95% H(2)O, 5% D(2)O indicated that the imino proton of the base opposite N14, G5, or T5, formed a weak hydrogen bond with N14. These conformations place the polar carboxamide functional group in the major groove with motional averaging on the intermediate time scale.

Amides↗

PubMed2001

Computational design of direct-bandgap semiconductors that lattice-match silicon.

Crystalline silicon is an indirect-bandgap semiconductor, making it an inefficient emitter of light. The successful integration of silicon-based electronics with optical components will therefore require optically active (for example, direct-bandgap) materials that can be grown on silicon with high-quality interfaces. For well ordered materials, this effectively translates into the requirement that such materials lattice-match silicon: lattice mismatch generally causes cracks and poor interface properties once the mismatched overlayer exceeds a very thin critical thickness. But no direct-bandgap semiconductor has yet been produced that can lattice-match silicon, and previously suggested structures pose formidable challenges for synthesis. Much recent work has therefore focused on introducing compliant transition layers between the mismatched components. Here we propose a more direct solution to integrating silicon electronics with optical components. We have computationally designed two hypothetical direct-bandgap semiconductor alloys, the synthesis of which should be possible through the deposition of specific group-IV precursor molecules and which lattice-match silicon to 0.5-1% along lattice planes with low Miller indices. The calculated bandgaps (and hence the frequency of emitted light) lie in the window of minimal absorption in current optical fibres.

Journal Article↗

PubMed2001

Ferrographic tracking of bacterial transport in the field at the narrow channel focus area, Oyster, VA.

The first results from an innovative bacterial tracking technique, ferrographic capture, applied to bacterial transport in groundwater are reported in this paper. Ferrographic capture was used to analyze samples during an October 1999 bacterial injection experiment at the Narrow Channel focus area of the South Oyster site, VA. Data obtained using this method showed that the timing of bacterial breakthrough was controlled by physical (hydraulic conductivity) heterogeneity in the vertical dimension as opposed to variation in sedimentsurface or aqueous chemical properties. Ferrographic tracking yielded results that compared well with results from other tracking techniques over a concentration range of 8 orders of magnitude and provided a low detection limit relative to most other bacterial tracking techniques. The low quantitation limit of this method (approximately 20 cells/mL) allowed observation of transport of an adhesion-deficient bacterium over distances greater than 20 m in the fine sand aquifer underlying this site.

Bacteria↗

PubMed2001

The effects of granulocyte colony-stimulating factor and neutrophil recruitment on the pulmonary chemokine response to intratracheal endotoxin.

Although G-CSF has been shown to increase neutrophil (polymorphonuclear leukocyte, PMN) recruitment into the lung during pulmonary infection, relatively little is known about the local chemokine profiles associated with this enhanced PMN delivery. We investigated the effects of G-CSF and PMN recruitment on the pulmonary chemokine response to intratracheal LPS. Rats pretreated twice daily for 2 days with an s.c. injection of G-CSF (50 microg/kg) were sacrificed at either 90 min or 4 h after intratracheal LPS (100 microg) challenge. Pulmonary recruitment of PMNs was not observed at 90 min post LPS challenge. Macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC) concentrations in bronchoalveolar lavage (BAL) fluid were similar in animals pretreated with or without G-CSF at this time. G-CSF pretreatment enhanced pulmonary recruitment of PMNs (5-fold) and greatly reduced MIP-2 and CINC levels in BAL fluid at 4 h after LPS challenge. In vitro, the presence of MIP-2 and CINC after LPS stimulation of alveolar macrophages was decreased by coculturing with circulating PMNs but not G-CSF. G-CSF had no direct effect on LPS-induced MIP-2 and CINC mRNA expression by alveolar macrophages. Pulmonary recruited PMNs showed a significant increase in cell-associated MIP-2 and CINC. Cell-associated MIP-2 and CINC of circulating PMNs were markedly increased after exposure of these cells to the BAL fluid of LPS-challenged lungs. These data suggest that recruited PMNs are important cells in modulating the local chemokine response. G-CSF augments PMN recruitment and, thereby, lowers local chemokine levels, which may be one mechanism resulting in the subsidence of the host proinflammatory response.

Animals↗

PubMed2001

Determination of arsenic species by capillary zone electrophoresis with large-volume field-amplified stacking injection.

Determination of arsenic species by large-volume field amplified stacking injection-capillary zone electrophoresis (LV-FASI-CZE) is reported in this paper. Whole column injection was employed. The optimum buffer pH for the separation of weak acids was discussed. It was found that the optimum buffer to analyze the stacked arsenate (As(V)), monomethylarsonate (MMA), and dimethylarsinate (DMA) was 25 mM phosphate at pH 6.5. However, the optimum buffer to analyze the concentrated arsenite (As(III)) was 20 mM phosphate - 10 mM borate at pH 9.28. The limits of detection of the method developed were 0.026 mg/L for As(III), 0.023 mg/L for As(V), 0.043 mg/L for MMA, and 0.018 mg/L for DMA. An enrichment factor of 34-100 for several arsenic species was obtained. In the end, this method was applied to determine the arsenic concentration in the environmental reference materials to show the usefulness of the method developed.

Arsenates↗

PubMed2001

Inactivity-Associated medical costs among US adults with arthritis.

OBJECTIVE: To analyze direct medical costs among US adults with arthritis and estimate the proportion associated with inactivity. METHODS: In the 1987 National Medical Expenditure Survey, arthritis was defined using questions on self-reported, doctor-diagnosed arthritis or rheumatism. Physical activity was defined using a self-report question on level of activity. Inactivity-associated medical costs were derived by subtracting costs for active adults from costs for inactive adults after controlling for functional limitation. RESULTS: Among 5,486 adults with arthritis, inactive persons had higher medical costs than did active persons in all demographic groups examined. In multivariate models adjusting for key covariates, the proportion of costs associated with inactivity averaged 12.4% ($1,250 in 2000 dollars) and ranged from 7.8% to 14.3% among various demographic groups. CONCLUSION: Inactivity-associated medical costs among persons with arthritis are considerable. Physical activity interventions may be a cost-effective strategy for reducing the burden of arthritis.

Activities of Daily Living↗

PubMed2001

Allelic loss and gain, but not genomic instability, as the major somatic mutation in primary hepatocellular carcinoma.

To identify genetic abnormalities in primary hepatocellular carcinoma (HCC), we performed microsatellite analysis (MSA) on 60 Chinese HCC specimens. Utilizing a semi-quantitative MSA and 292 highly polymorphic markers spanning all 22 autosomes, we found that somatic allelic imbalance (AI) occurred frequently in HCC. To evaluate the nature of the AI, comparative genomic hybridization was performed on 20 HCC specimens. The combined use of these two methods revealed frequent allelic loss on 17p, 9p21-p23, 4q, 16q21-q23.3, 13q, 8p21-p23, and 6q24-q27, whereas there was frequent allelic gain on 1q, 17q, and 8q24. The region with the highest incidence of genomic imbalance was 17p13 (65%), followed by 9p21-p23 (55%), 4q (35-51%), 16q21-q23.3 (52%), 17p12 (49%), 13q (39-46%), 8p21-p23 (41-45%), 8q24 (41%), and 1q32 (40%). In addition, aberrations of 19p13.3, 16p13.3, 13q33-q34, 9q13-31, and 7q were reported for the first time. The presence of a close correlation of 17p13 deletion with abnormalities of some other loci implies that 17p13 could play a crucial role in oncogenesis. Interestingly, microsatellite instability was rarely seen in our patients, in contrast to that observed in European HCC samples.

Adult↗

PubMed2001

Accuracy of sentinel node biopsy in predicting nodal status in patients with breast carcinoma.

BACKGROUND AND OBJECTIVES: While sentinel lymph node biopsy is considered by many to have replaced axillary node dissection in the management of breast cancer, concerns remain regarding false-negative results. METHODS: To investigate the accuracy of sentinel node biopsy, we reexamined all sentinel and nonsentinel nodes with multilevel sectioning and immunohistochemical staining in 42 consecutive cases of breast cancer in which sentinel node biopsy was performed and followed by axillary dissection. RESULTS: By routine hematoxylin and eosin (H&E) staining, 34% of patients were found to be node positive, with no cases of false-negative sentinel node biopsy. Reevaluation of 775 negative sentinel and nonsentinel nodes with an additional two levels and immunohistochemistry identified three "node-negative" patients who had micrometastases in the sentinel node, increasing detection in 8% of cases. More important, is the fact however, that there were no cases where additional sections and immunohistochemistry identified metastases in nonsentinel nodes that had bypassed the sentinel node. The accuracy of the sentinel node in predicting the nodal status was 100%. CONCLUSIONS: Cytokeratin immunohistochemistry will identify more patients with nodal micrometastases; however, it was unable to identify any cases where micrometastases were present in nonsentinel nodes when the sentinel node was negative. The status of the sentinel node accurately identifies the status of the axillary basin.

Adult↗

PubMed2001

Characterization of human cleaved N-CAM and association with schizophrenia.

The neural cell adhesion molecule (N-CAM) is a cell recognition molecule involved in cellular migration, synaptic plasticity, and CNS development. A 105- to 115-kDa isoform of N-CAM (cleaved N-CAM or cN-CAM) is increased in schizophrenia in hippocampus, prefrontal cortex, and CSF. We purified and partially characterized cN-CAM, a putative novel isoform, and confirmed that the first 9 amino acids were identical to exon 1 of N-CAM, without the signal sequence. Analysis of trypsin-digested cN-CAM fragments by matrix-assisted laser desorption ionization on a time-of-flight mass spectrometer (MALDI-TOF) yielded peptides that could be identified as being derived from the first 548 amino acid residues of the expected N-CAM amino acid sequence. Immunological identification with four specific N-CAM antisera directed toward cytoplasmic, secreted, variable alternative spliced exon, or GPI epitopes failed to indicate other known splice variants. Neuraminidase treatment of cN-CAM produced a minor alteration resulting in a faster migrating immunoreactive band, indicating partial glycosylation of cN-CAM. Membranous particles from cytosolic brain extract containing cN-CAM were obtained by ultracentrifugation; however, CSF contained few such particles. cN-CAM and synaptophysin were colocalized on these particles. Both cN-CAM and N-CAM 180 were present in synaptosomal preparations of human brain. Following incubation of synaptosomes or brain tissue without protease inhibitors, N-CAM 180 was degraded and cN-CAM was increased. A cN-CAM-like band was present in human fetal neuronal cultures, but not in fetal astrocyte cultures. Thus, cN-CAM represents a protease- and neuraminidase-susceptible fragment possibly derived by proteolytic cleavage of N-CAM 180. An enlargement in ventricular volume in a group of adult patients with schizophrenia over a 2-year interval was found to be correlated with CSF cN-CAM levels as measured at the time of the initial MRI scan (r = 0.53, P = 0.01). cN-CAM is associated with ventricular enlargement; thus, the release of N-CAM fragments may be part of the pathogenic mechanism of schizophrenia in vulnerable brain regions such as the hippocampus and prefrontal cortex. Alternatively, the increases in cN-CAM in schizophrenia may be a reflection of a more general abnormality in the regulation of proteolysis or of extracellular matrix stability.

Adult↗

PubMed2001

Automated data collection with a Tecnai 12 electron microscope: applications for molecular imaging by cryomicroscopy.

In high-resolution biological electron microscopy, the speed of collection of large numbers of high-quality micrographs is a rate-limiting step in the overall process of structure determination. Approaches to speed up data collection can be very useful, especially in "single-molecule" microscopy of large multiprotein and protein-nucleic acid complexes, where many thousands of individual molecular images need to be averaged to determine the three-dimensional structure. Toward this end, we report the development of automated low-dose image acquisition procedures on a Tecnai 12 electron microscope using the scripting functionality available on the microscope computer. At the lowest level of automation, the user is required to select regions of interest that are to be imaged. All subsequent steps of image acquisition are then carried out automatically to record high-resolution images on either film or CCD, at desired defocus values, under conditions that satisfy user-specified limits for drift rates of the specimen stage. At the highest level of automation, determination of the best grid squares and the best regions suitable for imaging are carried out automatically. A medium level of automation is also available in which the user can designate the most promising grid squares manually and leave the process of finding the best holes in those grid squares to the microscope computer. We also show that all steps subsequent to insertion of the specimen in the microscope can be carried out remotely by connecting to the microscope computer via the Internet. Both features are implemented using Windows NT and Web-based tools and provide tools for automated data collection on any Tecnai microscope from any location.

Cryoelectron Microscopy↗

PubMed2001

Role of the oncogenic Raf-1 in orchestration of discrete nuclear factor-kappaB-activating pathways.

Raf-1, a key kinase in the Ras signaling pathway, plays critical roles in cell differentiation, proliferation, and tumorigenesis. However, knowledge of the Raf-1 in inflammation is limited. Using an inducible oncogenic Raf-1, we show that the Raf-1 orchestrates the discrete NF-kappaB activating pathways. While the Raf-1 activation induces a modest IkappaB degradation by enhancing the basal IkappaB kinase activity, it contradictorily suppresses the proinflammatory cytokine inducible IkappaB kinase complex, leading to an inhibition of TNF-alpha- and IL-1beta-induced NF-kappaB activation. Despite considerable degrees of overlap, LPS signaling is not affected by Raf-1. By either conditionally reducing Raf-1 activity or completely disrupting the Raf-1 signaling by PD98059, a specific inhibitor of MEK1, the otherwise inhibited cytokine responses can be restored. Moreover, when the activity of Raf-1 is up-regulated during the cell cycle progression from the G(0) phase to the late G(1) phase, the enhanced Raf-1 activity suffices to shift the TNF-alpha response from the sensitive to the insensitive state. Together, these studies elucidate a mechanism by which signaling outputs are shaped by the intracellular Raf-1, thus explaining the "cellular context"-dependent cytokine response.

Animals↗

PubMed2001

Human lactoferrin in the milk of transgenic mice increases intestinal growth in ten-day-old suckling neonates.

Regulatory roles and a signaling receptor have been proposed for the milk protein lactoferrin (Lf), but none has been definitively characterized. Nichols and colleagues (1987) observed that human lactoferrin (hLf) stimulated thymidine incorporation into the DNA of rat intestinal crypt cells. We tested the hypothesis that chronic Lf administration stimulates intestinal growth by studying neonatal mice suckling transgenic dams secreting about 12 mg/mL hLf in their milk. Specifically, nontransgenic litters were adjusted to eight pups each and cross-fostered to transgenic dams. Controls were pups suckling nontransgenic dams of the same strain. On day 10 postpartum pups were weighed, sacrificed, and the small intestines were weighed, measured, and stored for later determination of enzyme activities. The results indicate that intestinal growth was increased in neonates suckling transgenic dams. The weight of the small intestine was increased about 27% when the pups received milk containing hLf. Intestinal length only increased about 6.5% suggesting that Lf in milk enhanced mucosal growth. The ratio of maltase to lactase in the duodenal segment of the small intestine, an indicator of maturation, was also significantly increased in the pups suckling transgenic milks. Our results imply that chronic oral consumption of human Lf promotes the growth and maturation of the intestinal mucosa, and suggest a possible therapeutic role for the agent in premature infants as well as in patients with bowel damage.

Animals↗