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Biomedical subjects

R H Miller

Publications and source records attributed to R H Miller.

At least 73 records · Page 4Linked to original sources
PubMed1997

Intestinal transit and absorption of soy protein in dogs depend on load and degree of protein hydrolysis.

Soy protein, in both intact and hydrolyzed forms, is widely used as the nitrogen source in infant and adult formulas. This protein is also consumed in vast quantities worldwide as soybean-based food products. Digestion is the rate-limiting step in the assimilation of proteins from the gut. As a result, intestinal transit must be slowed when a higher load of protein is available or when this nutrient is delivered in the intact rather than hydrolyzed form. However, little information is available on the effect of load and degree of hydrolysis of soy protein on intestinal transit and protein absorption. To test the hypothesis that inhibition of intestinal transit and protein absorption depend on the load of soy protein and the state of hydrolysis of this nutrient, we compared intestinal transit and protein absorption in dogs equipped with duodenal and midintestinal fistulas during intestinal perfusion with 0, 50, 100, or 200 g/L solutions of intact soy protein versus 0, 100, 200, 300, or 400 g/L solutions of hydrolyzed soy protein. We found that intestinal transit was slowed in a load-dependent fashion by intact (P < 0.001) and hydrolyzed (P < 0.05) soy protein. Soy protein inhibited intestinal transit more potently in the intact than hydrolyzed form (P < 0.05). A greater amount of protein was absorbed by the proximal half of the small intestine when soy protein was delivered in the hydrolyzed than intact form (P < 0.05), and the efficiency of protein absorption was maintained at a high and nearly constant level of 82.6 to 87.4% for intact soy protein and 89.0 to 92.3% for hydrolyzed soy protein. We conclude that in dogs intestinal transit and absorption of soy protein depend on the load and the degree of protein hydrolysis.

Animals↗
PubMed1997

Partially purified soy hydrolysates retard proliferation and inhibit bacterial translocation in cultured C2BBe cells.

Hydrolyzed soybean isolates SP-A and SP-B (Abbott Laboratories, OH), developed for use in enteral nutritional products, were tested in cultures of C2BBe cells, a colonic adenocarcinoma cell line with enterocytic differentiation, to evaluate effects on cell growth, maturation and ability to resist infection by enteric bacteria. SP-A delayed formation of confluent monolayers by 10 d compared with cells cultured without SP-A. SP-A also caused a retardation in the development of intercellular tight junctions as measured by transmonolayer electrical resistance (TER). SP-B had no effect on cell proliferation or TER of intestinal cell cultures. SP-A and SP-B enhanced the development of the brush border enzymes alkaline phosphatase and isomaltase over a 28 d period. By these criteria, SP-A and SP-B appear to affect intestinal epithelial cell development in culture. When C2BBe monolayers were exposed to the enteric bacteria, Salmonella typhimurium or Salmonella typhi, an inhibition of the passage of S. typhi was seen in cultures with SP-A and SP-B. No effect on the passage of S. typhimurium was seen with either soy isolate. Partially purified soy isolates therefore impart resistance to selected enteroinvasive bacteria. Addition of soy hydrolysates to the media of cultured intestinal cells may serve as a rapid and economical screening mechanism for preclinical trials that would test the therapeutic benefits of soybean isolates.

Adenocarcinoma↗
PubMed1997

Perioperative transfusion, postoperative infection, and recurrence of head and neck cancer.

BACKGROUND: Immunologic effects of perioperative transfusion and postoperative infection have been purported to influence cancer recurrence rates. METHODS: Records of all head and neck cancer patients having surgical extirpation of the primary tumor and/or regional nodes at our institution over a 5-year period were reviewed. Time to recurrence was the outcome measure. All variables were evaluated via univariate analysis using log rank tests, with Cox proportional hazards used for multivariate analyses. RESULTS: Univariate analysis identified the following as potential prognostic factors associated with recurrence: nodal stage, total lymphocyte count, overall stage, amount transfused, occurrence of a transfusion, and the American Society of Anesthesiologists status. Various backward stepwise multivariate regression models showed that neither transfusion nor postoperative infection independently influenced recurrence. However, transfusion of 3 or more units did surface as an independent contributor to recurrence, and in certain subgroups there was a trend toward improved survival for those who had a postoperative infection. CONCLUSIONS: In this series, neither perioperative transfusion nor postoperative infection independently influenced recurrence.

Aged↗
PubMed1997

Evaluation of selected antibiotic residue screening tests for milk from individual goats.

Because somatic cell counts (SCC) of caprine milk are higher than SCC of bovine milk, the performance of antibiotic residue tests for screening bovine milk was investigated for caprine milk. Eighty-five does that were free of antibiotic usage for at least 30 d and that were free of clinical mastitis were sampled at three milkings during a 37-d period. At each sampling, foremilk was collected for bacteriological analysis, and composite bucket milk samples were collected for antibiotic testing and SCC. Day of lactation, parity, 305-d mature equivalent milk yield, and SCC averaged 221 d (57 to 577 d), 2.3 lactations (one to nine lactations), 1160 kg (623 to 1750 kg), and 2.2 x 10(6)/ml (0.3 to 30.7 x 10(6)/ml), respectively. The mean Dairy Herd Improvement Association test day milk yield for the month of sample collection was 3 kg (1.4 to 6.4 kg). Intramammary infections were present in 54% of the goats and in 36% of the udder halves. Assays included positive (5 and 10 ppb of penicillin-G and 50 ppb of ceftiofur) and negative controls that had been prepared in caprine milk and controls supplied by the manufacturers. One false-negative outcome and one false-positive outcome were recorded. For one sampling day, a positive linear relationship existed between SCC and the results of one test, and a quadratic relationship existed between SCC and the results of another test. The antibiotic residue screening tests for milk from individual goats adequately identified milk that was free of antibiotic. These tests are therefore recommended for use with caprine milk.

Animals↗
PubMed1997

A comparison of three methods for estimating the requirements for medical specialists: the case of otolaryngologists.

OBJECTIVE: To compare three methods of computing the national requirements for otolaryngologists in 1994 and 2010. DATA SOURCES: Three large HMOs, a Delphi panel, the Bureau of Health Professions (BHPr), and published sources. STUDY DESIGN: Three established methods of computing requirements for otolaryngologists were compared: managed care, demand-utilization, and adjusted needs assessment. Under the managed care model, a published method based on reviewing staffing patterns in HMOs was modified to estimate the number of otolaryngologists. We obtained from BHPr estimates of work force projections from their demand model. To estimate the adjusted needs model, we convened a Delphi panel of otolaryngologists using the methodology developed by the Graduate Medical Education National Advisory Committee (GMENAC). DATA COLLECTION/EXTRACTION METHODS: Not applicable. PRINCIPAL FINDINGS: Wide variation in the estimated number of otolaryngologists required occurred across the three methods. Within each model it was possible to alter the requirements for otolaryngologists significantly by changing one or more of the key assumptions. The managed care model has a potential to obtain the most reliable estimates because it reflects actual staffing patterns in institutions that are attempting to use physicians efficiently. CONCLUSIONS: Estimates of work force requirements can vary considerably if one or more assumptions are changed. In order for the managed care approach to be useful for actual decision making concerning the appropriate number of otolaryngologists required, additional research on the methodology used to extrapolate the results to the general population is necessary.

Data Interpretation, Statistical↗
PubMed1996

Density-dependent feedback inhibition of oligodendrocyte precursor expansion.

The myelin sheath in the vertebrate CNS is formed by oligodendrocytes. The number of oligodendrocytes in a mature axon tract must be sufficient to myelinate all appropriate axons. How the number of oligodendrocytes is matched to axonal requirements and whether such matching involves axon-oligodendrocyte signaling or intrinsic oligodendrocyte self-regulation are not clear. Using a combination of in vitro analyses, we demonstrate that oligodendrocyte precursors closely regulate their numbers through interactions between adjacent precursors. In low-density rat spinal cord cultures, the number of oligodendrocyte lineage cells increases rapidly. The addition of large numbers of oligodendrocyte precursors substantially reduces precursor expansion and results in a normalization of oligodendrocyte lineage cell numbers in the cultures over time. Thus, the number of oligodendrocyte lineage cells that develop appears dependent on the density of oligodendrocyte lineage cells. This normalization of cell number is reflected in assays of clonal potential and proliferation. For example, precursors gave rise to fewer progeny and proliferated less at high density. Reduced precursor expansion at high density was not attributable to the depletion of growth factors. Cocultures of high and low densities did not inhibit precursor expansion in low-density cultures, suggesting the requirement for local cell-cell interactions. The inhibition of precursor expansion was cell-type-specific and dependent on the presence of oligodendrocyte lineage cells. We propose that this density-dependent feedback inhibition of oligodendrocyte precursor expansion may play a primary role in regulating the number of oligodendrocytes in the developing spinal cord.

Animals↗
PubMed1996

The origin of spinal cord oligodendrocytes is dependent on local influences from the notochord.

During spinal cord development, oligodendrocytes originate in a discrete region of the ventral ventricular zone. What regulates this initial localization of oligodendrocyte precursors is unclear. Using a combination of notochord transplantations in vivo and co-culture experiments, we demonstrate that the origin of chick spinal cord oligodendrocytes is dependent on local influences from the notochord. In stage 10-12 dorsal chick spinal cord, Mab O4+ oligodendrocyte precursors were induced both in vivo by isochronic transplantation of an additional notochord adjacent to the dorsal neural tube and in vitro by co-culture of notochord and dorsal neural tube. Heterochronic transplantations demonstrated that the notochord was capable of inducing O4+ cells in adjacent neural tube until stage 12 and that the competence of the dorsal neural tube to respond to this inductive signal declined after stage 10. During normal development the ventral neural tube is competent to develop oligodendrocytes independent of the notochord by stage 10. The induction of oligodendrocytes by the notochord may either reflect a direct interaction or be mediated through other ventrally located cells such as the floor plate. In the majority of experimental animals the appearance of ectopic oligodendrocyte precursors was correlated with local floor plate formation.

Animals↗
PubMed1996

Conference summary: novel HIV therapies--from discovery to clinical proof of concept.

In this report we have highlighted only a few examples of the extensive efforts underway to better understand the process of HIV pathogenesis, to develop new therapeutic agents to inhibit virus replication, and to identify strategies to restore damage done to the immune system during HIV disease progression. It is expected that progress in these areas will continue to advance, and that development of more effective therapies will lead to comprehensive multifaceted, multipronged treatment regimens.

HIV Infections↗
PubMed1996

A novel form of migration of glial precursors.

During development of the vertebrate central nervous system, many types of neural precursors originate in the ventricular zone of the central nervous system (CNS) and migrate through the neuropil to their final destination. In embryonic rat spinal cord, the ventral ventricular zone gives rise to neurons, astrocytes, and oligodendrocyte precursors. We have used a spinal cord stripe preparation to examine the migration of neural precursors from different regions of the spinal cord ventricular zone in vitro. Astrocyte and oligodendrocyte precursors, neurons, and neurites all emigrated from stripes of embryonic day 14 (E14) rat ventral spinal cord while only neurites emigrated in significant numbers from stripes of E14 dorsal spinal cord. The first wave of migrating cells from E14 ventral spinal cord stripes comprised a population of A2B5+ astrocyte precursors that exhibited a semicircular or ellipsoid morphology and showed an unusual form of lamellipodia-based motility. These cells were highly motile, migrating at rates of approximately 20 microns/h. The cortical region of the rapidly translocating astrocyte precursors contained high levels of actin microfilaments oriented in a circumferential band, but few microtubules. In their morphology, cytoskeletal organization, and rapid translocation, this subpopulation of vertebrate CNS glial precursors more closely resemble epidermal keratocytes than other neural cells. The rapid translocation exhibited by A2B5+ astrocyte precursors may reflect a role in CNS wound healing and be responsible for the rapid spread of some forms of CNS glial tumors.

Animals↗
PubMed1996

Oligodendrocyte origins.

In the adult vertebrate CNS, oligodendrocytes are ubiquitously distributed throughout white matter. By contrast, in the embryonic CNS, recent studies suggest that oligodendrocyte precursors arise in a discrete ventral location. Thus, local ventral environmental signals that contribute to the overall patterning of the CNS are likely to influence the initial appearance of oligodendrocyte precursors. Oligodendrocyte precursors subsequently disperse through the CNS by mechanisms that remain elusive. While the program to differentiate to oligodendrocytes appears to be cell autonomous, the local environment may regulate the precise temporal and spatial patterning of myelination.

Animals↗
PubMed1996

Protein absorption depends on load-dependent inhibition of intestinal transit in dogs.

Ileal perfusion of protein slows intestinal transit. Because optimal absorption of nutrients requires adequate time in contact with the mucosa, slowed intestinal transit may increase protein absorption by increasing the residence time of nutrients in the small intestine. Although protein supplements are routinely added to enteral feeding to correct protein malnutrition, little information is available on the effect of increasing the load of protein on intestinal transit and the efficiency of protein absorption. In six dogs equipped with duodenal and midintestinal fistulas, intestinal transit and the efficiency of protein absorption (percentage protein absorbed as estimated from the output of midintestinal fistula) were compared during intestinal perfusion with 0-, 50-, 100-, and 200-g/L solutions of a whey-based protein supplement. We found that intestinal transit slowed in a load-dependent fashion (P < 0.05); the amount of protein absorbed within the proximal one-half of the small intestine increased in a load-dependent fashion (P < 0.05) as intestinal transit slowed, and the percentage protein absorbed (reflecting the efficiency of protein absorption) was maintained at a high and nearly constant value of 66.5-72.5% across protein loads of 9-36 g. We conclude that enhanced protein absorption is associated with a load-dependent inhibition of intestinal transit.

Animals↗
PubMed1996

A double-blind, prospective, randomized study of glutamine-enriched compared with standard peptide-based feeding in critically ill patients.

Arterial and venous plasma amino acids were determined in 28 intensive care patients randomly assigned to receive 10 d of isoenergetic, isonitrogenous feedings that differed sixfold in glutamine content. Subjects were generally well-matched for age, injury severity, and disease diagnoses. Nasojejunal feedings were started within 48 h of admission. Data were analyzed from those 19 subjects still receiving > or = 50 mL feeding/h on day 5. Both groups had comparable gastric residuals, stool frequency, and delivered nitrogen and energy. At study initiation, all subjects had relative hypoaminoacidemia, with day 1 venous glutamine concentrations down 26% compared with reference values. Plasma glutamine rose to comparable concentrations with feeding of either diet. There were, however, significant (P < 0.05) increases in arterial or venous plasma total, indispensable, and branched-chain amino acids of 125-144% by day 5 only in patients fed the standard control diet. The phenylalanine-tyrosine ratio was elevated on day 1 in both groups (1.3-1.4) but decreased significantly only in the glutamine-supplemented group (1.1 compared with 1.4) by day 5. Glutamine supplementation blunted the hyperaminoacidemia and elevated aromatic amino acid response to injury.

APACHE↗
PubMed1996

Nasal septal squamous cell carcinoma: a chart review and meta-analysis.

Squamous cell carcinoma of the nasal septum occurs infrequently and is often misdiagnosed because its symptoms are similar to everyday rhinologic complaints. The published series have been too small to determine the best form of treatment for this cancer. The authors of this study retrospectively reviewed nasal septal squamous cell carcinomas treated at three university-affiliated hospitals over a 30-year period. Sixteen primary tumors were identified and reviewed for presentation, staging, treatment, recurrence patterns, and risk factors. The authors then combined their findings with those of suitable literature series and performed a meta-analysis to evaluate predictors of survival. There were too few patients in each stage and treatment group to significantly determine the optimal treatment for nasal septal squamous cell carcinoma. However, based on the present study and the literature series, the authors suggest that small lesions may be confidently treated with either radiation or surgery and that combined therapy may be reserved for more advanced tumors.

Aged↗
PubMed1996

Mapping economic trait loci for somatic cell score in Holstein cattle using microsatellite markers and selective genotyping.

Marker-assisted selection (MAS) uses genetic marker genotypes to predict an animal's production potential and will provide additional selection information for progeny testing. With the discovery of highly polymorphic microsatellite markers, the tools now exist to begin the search for economic trait loci (ETL), which is the first step toward MAS. The objective of this study was to identify ETL for somatic cell score in an existing Holstein population. Using the granddaughter design, sons from seven grandsire families were genotyped with 20 autosomal microsatellites from five chromosomes (4, 8, 13, 17, 23), with an emphasis on chromosome 23, which is the location of the bovine major histocompatibility complex (BoLA). Selective genotyping was used to reduce the number of genotypes required, in which the 10 highest and 10 lowest sons from the phenotypic distribution curve were tested (140 sons in seven families). One marker (513), located near BoLA, showed evidence of an ETL in three of five polymorphic families. Additional sons were genotyped from the five families to estimate the effect and to compare selective and 'complete' genotyping. Both methods detected an ETL at marker 513, but in different families. This study provides evidence of the usefulness of microsatellite markers and the granddaughter design in the detection of ETL; however, additional markers need to be evaluated to determine the usefulness of selective genotyping. Based on the results from the 20 studied markers, the most likely position of a somatic cell score ETL lies near marker 513, located on chromosome 23.

Alleles↗
PubMed1996

Long PCR and its application to hepatitis viruses: amplification of hepatitis A, hepatitis B, and hepatitis C virus genomes.

In this study we amplified virtually the entire genomes of hepatitis A virus (a member of the Picornaviridae family), hepatitis B virus (a member of the Hepadnaviridae family), and hepatitis C virus (a member of the Flaviviridae family) by using the recently described technique of long PCR. In order to do this, we first demonstrated, using the lambda phage, that long PCR can be made highly sensitive and the sensitivity can be further enhanced by nested long PCR. We also showed, using tobacco mosaic virus as a model, that a reverse transcriptase reaction can be linked to a long PCR, enabling the nearly full-length amplification of the genomes of RNA viruses. We then applied these techniques to serial dilutions of titrated stocks of well-characterized strains of hepatitis A, B, and C viruses. We amplified the nearly full-length sequence of each of these viruses from a small number of viral genomes, demonstrating the sensitivity of the process.

Bacteriophage lambda↗
PubMed1996

A hydrophobic heptad repeat of the core protein of woodchuck hepatitis virus is required for capsid assembly.

The capsid particle of hepadnaviruses is assembled from its dimer precursors. However, the mechanism of the protein-protein interaction is still poorly understood. A small region in the capsid protein of woodchuck hepatitis virus (WHV) contains four hydrophobic residues, including leucine 101, leucine 108, valine 115, and phenylalanine 122, that are conserved and spaced every seventh residue in the primary sequence to form a hydrophobic heptad repeat (hhr). A hydrophobic force often plays an important role in the interaction of proteins. Therefore, to investigate the role of this region in capsid assembly, we individually changed the codons specifying these four hydrophobic amino acids to codons specifying alanine or proline. In addition, we examined the in vivo infectivity of a WHV genome bearing a naturally occurring single amino acid change (histidine 104-->proline) in the hhr region. The phenotype of each altered genome was determined in both eukaryotic and prokaryotic systems by a capsid protein assay and electron microscopic examination. We show that replacement of any one of the four hydrophobic residues with alanine did not prevent capsid assembly. However, assembled capsid particles were not detected if combinations of any two of the four residues were substituted with alanines or if the spacing of these four hydrophobic residues was changed. An individual introduction of a proline (which dramatically changes the secondary structure of proteins) into different positions of this small region also abolished capsid assembly in vitro or viral replication in vivo. These results suggested that the hhr region of the core protein of WHV was critical for capsid assembly.

Amino Acid Sequence↗