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R K Miller

Publications and source records attributed to R K Miller.

At least 55 records · Page 3Linked to original sources
PubMed1998

Transport and endogenous release of vitamin B12 in the dually perfused human placenta.

The kinetics for vitamin B12, cobalamin (Cbl), transfer across the human placenta, and the retention of the endogenous Cbl and its release into the maternal and fetal compartments were investigated in a dually perfused human term placenta in vitro. After 4 hours of perfusion following a single bolus injection (peak maternal perfusate 94 fmol/ml) of 57Co-Cbl into the maternal reservoir, the maternal [57Co-Cbl] rapidly decreased whereas the fetal [57Co-Cbl] was only 9% of the final maternal [57Co-Cbl]. Even though there was a limited transfer of 57Co-Cbl to the fetus, the placenta rapidly accumulated Cbl. At 4 hours, 18% of the initial 57Co-Cbl dose was in the placenta; only 3% of the initial dose was in the fetal perfusate. Also after 4 hours, [57Co-Cbl] was bound > 95% to transcobalamin (TC)I/III-like proteins in the maternal perfusate, whereas Cbl was bound to TCI/III- and TCII-like proteins with some free in the fetal perfusate. In the cytosol, > 95% of the [57Co-Cbl] was bound (80% to TCII-like and 19% to TCI/III-like proteins). When no exogenous Cbl was added, total endogenous [Cbl] in the maternal circulation increased with time during 8 hours of perfusion at a rate of 0.25 +/- 0.12 pmol/gm per hour. Only 2% of this Cbl was free, whereas 98% was bound to specific binding proteins. Neither plateau values nor equilibration with the fetal side were noted. In the fetal circulation, there was a release of Cbl at a rate of 0.015 +/- 0.003 pmol/gm per hour, which was 99.99% bound. Thus the human placenta rapidly concentrates Cbl in the perfused lobule with little distribution of Cbl to nonperfused areas. Therefore, the human placenta modulates the asymmetric transfer of vitamin B12 on the basis of release of specific Cbl-binding proteins (TCI/III- and TCII-like) into the maternal and fetal perfusates.

Female↗
PubMed1998

Candidate gene analysis of GH1 for effects on growth and carcass composition of cattle.

We present an approach to evaluate the support for candidate genes as quantitative trait loci (QTLs) within the context of genome-wide map-based cloning strategies. To establish candidacy, a bacterial artificial chromosome (BAC) clone containing a putative candidate gene is physically assigned to an anchored linkage map to localise the gene relative to an identified QTL effect. Microsatellite loci derived from BAC clones containing an established candidate gene are integrated into the linkage map facilitating the evaluation by interval analysis of the statistical support for QTL identity. Permutation analysis is employed to determine experiment-wise statistical support. The approach is illustrated for the growth hormone 1 (GH1) gene and growth and carcass phenotypes in cattle. Polymerase chain reaction (PCR) primers which amplify a 441 bp fragment of GH1 were used to systematically screen a bovine BAC library comprising 60,000 clones and with a 95% probability of containing a single copy sequence. The presence of GH1 in BAC-110R2C3 was confirmed by sequence analysis of the PCR product from this clone and by the physical assignment of BAC110R2C3 to bovine chromosome 19 (BTA19) band 22 by fluorescence in situ hybridisation (FISH). Microsatellite KHGH1 was isolated from BAC110R2C3 and scored in 529 reciprocal backcross and F2 fullsib progeny from 41 resource families derived from Angus (Bos taurus) and Brahman (Bos indicus). The microsatellite KHGH1 was incorporated into a framework genetic map of BTA19 comprising 12 microsatellite loci, the erythrocyte antigen T and a GH1-TaqI restriction fragment length polymorphism (RFLP). Interval analysis localised effects of taurus vs. indicus alleles on subcutaneous fat and the percentage of either extractable fat from the Iongissimus dorsi muscle to the region of BTA19 harbouring GH1.

Animals↗
PubMed1998

The kinesin-related proteins, Kip2p and Kip3p, function differently in nuclear migration in yeast.

The roles of two kinesin-related proteins, Kip2p and Kip3p, in microtubule function and nuclear migration were investigated. Deletion of either gene resulted in nuclear migration defects similar to those described for dynein and kar9 mutants. By indirect immunofluorescence, the cytoplasmic microtubules in kip2Delta were consistently short or absent throughout the cell cycle. In contrast, in kip3Delta strains, the cytoplasmic microtubules were significantly longer than wild type at telophase. Furthermore, in the kip3Delta cells with nuclear positioning defects, the cytoplasmic microtubules were misoriented and failed to extend into the bud. Localization studies found Kip2p exclusively on cytoplasmic microtubules throughout the cell cycle, whereas GFP-Kip3p localized to both spindle and cytoplasmic microtubules. Genetic analysis demonstrated that the kip2Delta kar9Delta double mutants were synthetically lethal, whereas kip3Delta kar9Delta double mutants were viable. Conversely, kip3Delta dhc1Delta double mutants were synthetically lethal, whereas kip2Delta dhc1Delta double mutants were viable. We suggest that the kinesin-related proteins, Kip2p and Kip3p, function in nuclear migration and that they do so by different mechanisms. We propose that Kip2p stabilizes microtubules and is required as part of the dynein-mediated pathway in nuclear migration. Furthermore, we propose that Kip3p functions, in part, by depolymerizing microtubules and is required for the Kar9p-dependent orientation of the cytoplasmic microtubules.

Base Sequence↗
PubMed1998

In vitro measurement of patellofemoral force after three types of knee replacement.

Using a new, non-invasive method, we measured the patellofemoral force (PFF) in cadaver knees mounted in a rig to simulate weight-bearing. The PFF was measured from 20 degrees to 120 degrees of flexion before and after implanting three designs of knee prosthesis. Medial unicompartmental arthroplasty with a meniscal-bearing prosthesis and with retention of both cruciate ligaments caused no significant change in the PFF. After arthroplasty with a posterior-cruciate-retaining prosthesis and division of the anterior cruciate ligament, the PFF decreased in extension and increased by 20% in flexion. Implantation of a posterior stabilised prosthesis and division of both cruciate ligaments produced a decrease in the PFF in extension but maintained normal load in flexion. There was a direct relationship between the PFF and the angle made with the patellar tendon and the long axis of the tibia. The abnormalities of the patellar tendon angle which resulted from implantation of the two total prostheses explain the observed changes in the PFF and show how the mechanics of the patellofemoral joint depend upon the kinematics of the tibiofemoral articulation.

Arthroplasty, Replacement, Knee↗
PubMed1998

Beef customer satisfaction: role of cut, USDA quality grade, and city on in-home consumer ratings.

An in-home beef study evaluated consumer ratings from moderate-to-heavy beef users as influenced by cut (top loin, top sirloin, and top round steaks), USDA quality grade (Top Choice, Low Choice, High Select, and Low Select), and city (Chicago, Houston, Philadelphia, and San Francisco). Consumers (n = 2,212) evaluated each steak for overall like (OLIKE), tenderness (TEND), juiciness (JUIC), flavor desirability (DFLAV), and flavor intensity (IFLAV) using 23-point hedonic scales (23 = like extremely, extremely tender, extremely juicy, like extremely, and an extreme amount of flavor; 1 = dislike extremely, not at all tender, not at all juicy, dislike extremely, and no flavor at all). A USDA grade x cut interaction existed for OLIKE (P < .05). Consumers rated top loin steaks highest (P < .05) in OLIKE and ranked Top Choice highest of all steaks (P < .05). Within the top loin, consumers were not (P > .05) able to distinguish OLIKE differences between Low Choice and High Select or between High Select and Low Select. For OLIKE, top sirloin was rated intermediate (P < .05) of the three cuts, and consumers were not able to detect (P > .05) USDA quality grade differences. For OLIKE, top round was the lowest-rated (P < .05) cut. However, consumers preferred (OLIKE, P < .05) Top Choice to the other USDA grades offered. Grade and city interacted to affect TEND, JUIC, DFLAV, and IFLAV. The cut x city interaction was significant for all palatability attributes. Cut and city affected customer satisfaction more than USDA quality grade. Tenderness and flavor were important and equal contributors to OLIKE, r = .85 and r = .86, respectively.

Adult↗
PubMed1997

Pharmacokinetic and toxicity studies of AZT (zidovudine) following perfusion of human term placenta for 14 hours.

Multiple exposures to AZT (Zidovudine) for 14 hr were examined in the dually perfused human term placental lobule in order to determine the pharmacokinetics of transfer, as well as several viability parameters of toxicity. In each experiment, three separate additions of AZT at a concentration of 3.8 mM was added to the maternal reservoir, and perfusate samples were obtained from both the maternal and the fetal compartments for determinations of AZT, glucose, lactate, oxygen, and human chorionic gonadotropin (hCG) concentrations. During 14 hr of continuous exposure to this high concentration of AZT, the production of hCG was significantly reduced by 75% when compared to the 2-hr control period before the administration of AZT. In addition, lactate production was reduced by 45% after AZT administration. Such changes in hCG and lactate production were not observed in separate experiments conducted over the same time interval, but with no AZT added. Based upon a lack of total perfusion fluid loss, changes in fetal arterial pressure, and histopathology, placental lobule integrity was maintained throughout the perfusion period. Further, AZT readily crossed the placenta into the fetal compartment reaching equilibrium with maternal levels within 60-90 min after addition of each administration of AZT. Based upon AZT levels in the fetal perfusate, AZT does not accumulate against a concentration gradient and therefore appears to be diffusion limited. Placental tissues obtained from perfused, partially perfused, and nonperfused regions at the conclusion of the experiment were analyzed for AZT levels. Substantial AZT levels in the nonperfused tissues indicated that AZT is a freely diffusible compound. The results of the current study demonstrate that high concentrations of AZT alter placental function resulting in reduced production of hCG and lactate.

Anti-HIV Agents↗
PubMed1997

Toxicity of cadmium in human trophoblast cells (JAr choriocarcinoma): role of calmodulin and the calmodulin inhibitor, zaldaride maleate.

Cadmium (Cd), the heavy metal, is toxic to the placenta. The objectives of this study were to determine if Cd toxicity is due to inhibition of placental or trophoblast cell proliferation through interactions with the intracellular calcium binding protein, calmodulin (CaM). Cd can replace calcium and thus interfere with CaM's function. Also, CaM inhibitors reverse selected toxic effects of Cd. The CaM inhibitor, zaldaride maleate, was used to determine if Cd inhibits trophoblast cell proliferation through interactions with CaM. JAr choriocarcinoma cells, a neoplastic trophoblast cell line which is similar to early human trophoblast cells, were selected to study this question. Cd (20 and 40 microM) inhibits JAr cell proliferation, as measured by cell number and BrdU incorporation. Zaldaride (10 and 20 microM) inhibits proliferation to a lesser extent; 100 microM is lethal. To determine if zaldaride alters actions of Cd, zaldaride and Cd are added simultaneously. Zaldaride (20 microM) and Cd (20 microM) together inhibit proliferation less than Cd alone, thus partially protecting cells. Metallothionein is induced in cells exposed to Cd, while zaldaride does not cause induction of this cellular defense mechanism protein. To determine if Cd inhibits proliferation through alterations of cell cycle, JAr cells enriched for G0/G1 phase were exposed to 20 microM Cd, 20 microM zaldaride, or 20 microM Cd plus 20 microM zaldaride for 24 hr. Cells remain in G0/G1 following Cd exposure; cells treated with 20 microM zaldaride progress through S phase and into G2. Zaldaride and Cd together allow JAr cells to leave G1 and enter S phase, partially relieving the cycle block produced by Cd. This study demonstrates a role for calmodulin in mediating the toxicity of Cd in trophoblast cell proliferation.

Antidiarrheals↗
PubMed1997

In vitro patellofemoral joint force determined by a non-invasive technique.

OBJECTIVE: To develop a method of measuring the magnitude, direction and point of application of the patellofemoral force (PFF), directly and non-invasively in three dimensions. DESIGN AND METHODS: The compressive PFF is replaced exactly with a tensile force applied to the front of the patella. The magnitude, direction and point of application of the tensile force are then measured. The technique was applied to six normal knees mounted in a 6 degree of freedom rig with quadriceps tendon tension force (QTF) applied to balance a flexing load and to simulate weight bearing. RESULTS: The PFF was greater than in previous more invasive in vitro studies but the results correlated well with recent theoretical analyses. At 20 degrees knee flexion the force was 75% of QTF. It increased to 100% of QTF at 60 degrees knee flexion and remained at this level at higher angles of flexion. The lateral vector of the PFF was small compared to the sagittal plane vector and became negligible beyond 60 degrees of knee flexion. The point of application of the PFF to the patella moved proximally and medially with knee flexion. CONCLUSIONS: A new and reliable method of measuring PFF non-invasively and in three dimensions has been developed. RELEVANCE: A new technique is described for measuring the PFF in vitro. The non-invasive nature of the technique makes it useful for studying the effect on the PFF of simulated pathological conditions, surgical procedures and different types of knee replacement.

Journal Article↗
PubMed1997

Effect of speaking into a passive resonator on stuttering frequency.

The effect on stuttering frequency of speaking into a passive resonator was investigated. Eight participants who stuttered read aloud with and without the benefit of the resonator. A statistically significant reduction of approximately 30% in stuttering frequency was observed while the participants spoke with the resonator. These and similar commercially available devices may be employed with individuals who stutter, particularly children, as a means of enhancing fluency.

Adolescent↗
PubMed1997

Performance, carcass, and palatability traits for cull cows fed high-energy concentrate diets for 0, 14, 28, 42, or 56 days.

Cull cows, thin to moderate in initial condition scores, were randomly assigned within breed to slaughter groups and fed a high-concentrate diet for 0, 14, 28, 42 or 56 d (n = 40). Carcass data were collected, and one side of each carcass was fabricated into boneless subprimals, lean trimmings, fat, and bone. Live and carcass weights, ADG, and dressing percentage increased through 28 d of feeding (P < .05), and lean firmness increased (P < .05) through 42 d of feeding. Adjusted preliminary yield grades and final yield grades increased (P < .05) with feeding, but not to levels requiring knife trimming of fat. Fat color became whiter (P < .05) but marbling was not affected (P > .05) by feeding. Weights of fat-free lean, fat, and bone and percentages of fat in soft tissues of cow carcasses increased (P < .05) by 28 d on feed. Overall steak tenderness was higher (P < .05) for cows fed 56 d than for cows fed 0 or 14 d. Warner-Bratzler shear force was not affected by feeding. Amounts of soluble collagen increased (P < .05) in the longissimus muscle between 0 and 28 d on feed, and total collagen decreased (P < .05) in the biceps femoris muscle between 0 and 42 d on feed. Continental European cow carcasses yielded more fat-free lean and less fat (P < .05) and dairy cows generally provided the most tender product across all slaughter periods. In general, sensory tenderness and yields of cow carcass components increased without requiring excessive trimming of fat by feeding cull beef and dairy cows for periods up to 56 d.

Animals↗
PubMed1997

Consumer evaluation of beef of known categories of tenderness.

A study was conducted to determine consumer perceptions of beef top loin steaks of known shear force and to evaluate how buying trends were modified by the tenderness and price variations of these steaks. Strip loins were cut into a 2.54-cm-thick steaks, and the center steak from each strip loin was used to determine Warner-Bratzler shear force. The remaining steaks were placed into one of the following shear force categories based on that shear force and color-coded accordingly: 1) 2.27 to 3.58 kg (Red); 2) 4.08 to 5.40 kg (White); and 3) 5.90 to 7.21 kg (Blue). Randomly recruited consumers were allowed to evaluate steaks and then purchase steaks based on their findings. A $1.10/kg price difference was placed between each category. Results of the analysis indicated that consumers were able to differentiate between the three categories of tenderness (P < .05). In addition, consumers gave higher (P < .05) juiciness and flavor ratings to Red steaks than to Blue steaks. Overall satisfaction was higher (P < .05) for Red steaks than for the other two categories of steaks. The following percentages of steaks were purchased: 1) Red, 94.6%; 2) White, 3.6%; and 3) Blue, 1.8%. These results suggest that consumers could discern between categories of tenderness and were willing to pay a premium for improved tenderness.

Animals↗
PubMed1997

A comparison of Warner-Bratzler shear force assessment within and among institutions.

Our objective was to compare measurement of Warner-Bratzler shear force of beef longissimus within and among institutions when each institution used its own protocol and when all institutions used a standardized protocol. In Exp. 1, each of five institutions (A, B, C, D, and E) received two adjacent steaks from each of 27 beef strip loins (longissimus lumborum). Warner-Bratzler shear force was measured for both steaks using the procedures normally used at each institution. In Exp. 2, each institution received two adjacent steaks from each of 45 strip loins. Shear force was measured for both steaks using a standardized protocol. In Exp. 1, Warner-Bratzler shear force was highest (P < .05) for A (4.7 kg) and lowest (P < .05) for B (2.9 kg). Repeatability of shear force was highest for A and C (.73 and .72), intermediate for D (.63), and lowest for B and E (.39 and .44). In Exp. 2, Warner-Bratzler shear force was highest (P < .05) for A (5.1 kg) and lowest (P < .05) for E (3.7 kg). Repeatability of shear force was highest for A (.87), intermediate for B, D, and E (.81, .75, and .80), and lowest for C (.67). Shear force values differed within and among institutions due to protocol, execution of the protocol, and instrument variation. Thus, comparisons of Warner-Bratzler shear force data among institutions are currently not valid. However, it is possible for institutions to obtain the same mean shear force value and have high repeatability if a standard protocol is properly executed with calibrated equipment.

Analysis of Variance↗
PubMed1997

Human placenta does not Reduce AZT (zidovudine) to 3'-amino-3'-deoxythymidine.

Human placental tissue and human trophoblast cells (JAr) were examined after exposure to the anti-HIV nucleoside analog AZT (Zidovudine) for the presence of 3'-amino-3'-deoxythymidine (AMT), a toxic catabolite. Placental cells were exposed to 7.6 mM AZT for 48 hr, and placental lobular tissue was perfused with 3.8 mM AZT for 14 hr. Cell homogenates were prepared, and supernatants were subjected to HPLC analysis. Despite large cellular concentrations of AZT, AMT was not detected in any of the samples analyzed. Exposure of JAr cells to this concentration of AZT produces a 72% inhibition of cell proliferation when compared with unexposed controls. Based upon the results of the current study, AMT was not formed by placental cells exposed to AZT and, thus, not a mechanism for toxicity after in vitro exposure to AZT.

Chromatography, High Pressure Liquid↗
PubMed1996

Energy charge monitoring via magnetic resonance spectroscopy 31P in the perfused human placenta: effects of cadmium, dinitrophenol and iodoacetate.

Phosphorus 31 nuclear magnetic resonance spectroscopy as a non-invasive technique was applied to monitor the metabolic activity of the human placenta during perfusion in vitro. During control perfusions (n = 3) there was an initial increase in adenosine triphosphate (ATP) and a fall in inorganic phosphate (Pi). Thereafter, however, the level of both ATP and Pi remained constant throughout the perfusion period (11 h). Additional biochemical parameters such as glucose consumption, lactate production and the release of hormones, human chorionic gonadotrophin (hGC). measured in the perfusate samples, were also used to assess the viability of the placental tissue. As with ATP, all these biochemical parameters under the control conditions showed a stable rate of metabolic activity throughout the length of the experiments. In additional experiments, the effect of the metabolic inhibitor dinitrophenol (n = 2) and dinitrophenol (DNP) together with iodoacetic acid (IOA, n = 2) were studied. DNP (0.1 mM) alone showed a slight decrease of all parameters. In contrast, the addition of IOA (0.1 mM) with DNP (0.1 mM) not only blocked the production of ATP but also produced a substantial impact on placental metabolic activity. The effect of a toxic dose of cadmium (20 nmol/ml) was studied also (n = 3). This dose of cadmium demonstrated no effect on phosphorus metabolism. However, the rate of glucose consumption and the release of hCG were significantly reduced.

Adenosine Triphosphate↗
PubMed1996

Influence of realimentation of mature cows on maturity, color, collagen solubility, and sensory characteristics.

Cull beef cows (n = 80) that had consumed similar grassland diets were assigned to one of four feeding periods (0, 28, 56, and 84 d) and subdivided into two groups fed either a high-energy, high-protein diet or a high-energy, low-protein diet. Treatments were designed to examine the effect of time on feed, dietary protein, and electrical stimulation on carcass traits, composition, shear force, sensory profile, collagen characteristics, and myoglobin state. Within 1 h of slaughter, the right side of each carcass was electrically stimulated, and the left side served as the control. The only trait influenced by protein level was longissimus muscle area, for which a high-protein diet resulted in larger (P < .05) longissimus muscle areas. Increased time on a high-energy diet increased USDA yield grade and sensory ratings; however, metmyoglobin and reduced myoglobin values decreased between 0 and 28 d on feed. Electrical stimulation improved lean color, shear force values, and sensory attributes. Electrical stimulation decreased shear force by 2.8 kg for 0-d carcasses. With subsequent days on feed, shear force values continued to decrease, but this effect was minimal in electrically stimulated carcasses. However, protein level did not significantly influence palatability and quality attributes. The greatest (P < .05) improvement in marbling score was observed in electrically stimulated carcasses from cows fed for 84 d. Additionally, feeding a high-protein diet for 84 d resulted in a slightly lower maturity score. Even though values for palatability and quality traits were improved by antemortem and postmortem treatments, the magnitude of improvement may not be great enough for steaks from mature fed cows to be considered as acceptable as steaks from young fed beef.

Aging↗
PubMed1995

Cellular adaptation to chronic cadmium exposure: intracellular localization of metallothionein protein in human trophoblast cells (JAr).

Trophoblast cells are the first embryonic cells that modulate the transfer of a variety of compounds (oxygen, amino acids, xenobiotics, metals) from the maternal to the fetal circulation in the human placenta. Human placental exposure to the toxic metal, cadmium (Cd) results in a decrease in the production of human chorionic gonadotropin (hCG), a decrease in the maternal to fetal transport of zinc (Zn), and trophoblastic necrosis. Thus, the ability of trophoblast cells to adapt to exposure to the toxic metal Cd has been considered crucial. In this study, the expression and intracellular localization of metallothionein (MT), a small molecular weight, metal binding protein, was examined in trophoblast cells (JAr) grown in normal media and in cells exposed chronically (6 months) to 2 microM CdCl2. Conventional and confocal fluorescence microscopy were used to examine the intracellular localization of MT protein in control cells and cells grown chronically in Cd. In unexposed trophoblast cells, MT protein was primarily perinuclear with low level, punctate expression in the cytosol. Following both chronic and 24 hour exposure to Cd, MT protein levels were increased (at least 3-fold in both chronic and acute exposures) and the protein was now concentrated inside the nucleus with a lacy, cytoskeletal pattern of expression in the cytosol. To determine if the nuclear accumulation of MT protein was dependent on new protein synthesis, control cells were exposed to CdCl2 (2 microM) and cycloheximide (2 micrograms/. ml) for 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Cadmium↗
PubMed1995

Health risks associated with prenatal metal exposure.

A symposium entitled Health Risks Associated with Prenatal Metal Exposure was held at the 33rd Annual Meeting of the Society of Toxicology (SOT) in Dallas, Texas. The symposium was cosponsored by the Metals and Reproductive and Developmental Specialty Sections of SOT and was designed to elaborate the health risks associated with in utero exposure to metals commonly found in the workplace and/or ambient environment on the mother and developing offspring. Epidemiological and toxicological evidence that demonstrates the health effects and underlying mechanisms associated with exposure to arsenic (As), lead (Pb), and methyl mercury (MeHg) were discussed, as well as the legal ramifications and personal implications associated with prenatal metal exposure. The following is a summary of each of the individual presentations.

Animals↗