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Biomedical subjects

R K Miller

Publications and source records attributed to R K Miller.

At least 91 records · Page 5Linked to original sources
PubMed1992

Development and preparation of lean meat products.

When the effect of food on human lipoprotein levels is tested, or when human consumption of dietary lipids must be controlled or limited, all food needs to be provided under controlled conditions to achieve consistent composition and sensory traits. It is especially important to control the composition of foods, particularly fat and fatty acid content. Because of the inherent biologic variability in the chemical composition of animal tissues (beef in particular), raw materials must be selected carefully and prepared under strict guidelines. In addition, chemical composition should be verified initially and during the production of the product to ensure the accuracy necessary for controlled dietary intake. Furthermore, the meat provided must be easy for the study subject to prepare, be of consistent serving size, and yet be highly palatable to maintain the subject's interest and participation. This article outlines the protocol for developing lean meat products for use in nutrition studies in which fat content must be controlled, especially those studies designed to examine the effect of fat content on human lipoproteins. Preliminary studies, procurement of raw materials, procedures for recipe selection, product preparation, and sampling procedures for verification of chemical composition are described. Our findings indicate that fat intake from beef, chicken, and fish can be controlled for use in nutrition studies.

Animals↗
PubMed1991

Carcinogenicity of diethylstilbestrol in the Wistar rat: effect of postnatal oral contraceptive steroids.

Diethylstilbestrol (DES) has been associated with vaginal neoplasia and malformations in humans. We have studied a test population of 504 female Wistar rats given diethylstilbestrol at from 0.0 to 0.5 mg/kg maternal body weight on days 18, 19, and 20 of gestation. Animals were euthanized in extremis, or at 2 years of age. The incidence of vaginal epithelial tumors was dose related. The types of epithelial tumors of the vagina were adenocarcinoma, squamous cell carcinoma, and mixed carcinoma, containing discrete adenomatous and squamous components. The incidence of vaginal epithelial tumors was determined to be dose related: rats exposed to 0 mg DES/kg maternal weight had an incidence of 0.6% (1 of 167 rats); 0.1 mg/kg, 4.1%; and 0.5 mg/kg, 4.3% (6 of 140); 25 mg/kg, 1.6% (1 of 63); and 50 mg/kg, 11.5% (3 of 26). Tumors of other reproductive tissues (mammary gland, ovary, oviduct, cervix, or uterus) demonstrated no discernible DES dose-response relationship. There was no oncogenic effect of postnatal administration of oral contraceptives (0 oral contraceptives, 31.25 micrograms/kg diet ethynylestradiol, and 31.25 micrograms/kg diet norethindrone or 104 micrograms/kg diet ethynylestradiol and 31.25 micrograms/kg diet norethindrone). Thus, vaginal tumors can be induced in a dose-related manner in the rat following in utero DES exposure. Oral contraceptive treatment did not increase the risk of neoplasia.

Adenocarcinoma↗
PubMed1991

Keratin incorporation into intermediate filament networks is a rapid process.

The properties of keratin-containing intermediate filament (IF) networks in vivo were studied following the microinjection of biotinylated keratin. Keratin-IFs were biotinylated, disassembled, and separated into type I and type II proteins by ion exchange chromatography. Recombination of these derivatized type I and type II keratins resulted in the formation of 10-nm diameter IF. The type I keratins were microinjected into epithelial cells and observed by immunofluorescence microscopy. Biotin-rich spots were found throughout the cytoplasm at 15-20 min after injection. Short biotinylated fibrous structures were seen at 30-45 min after injection, most of which colocalized with the endogenous bundles of IF (tono-filaments). By 1 1/2 to 2 h after microinjection, extensive biotinylated keratin IF-like networks were evident. These were highly coincident with the endogenous tonofilaments throughout the cell, including those at desmosomal junctions. These results suggest the existence of a relatively rapid subunit incorporation mechanism using numerous sites along the length of the endogenous tonofilament bundles. These observations support the idea that keratin-IFs are dynamic cytoskeletal elements.

Animals↗
PubMed1991

Fetal drug therapy: principles and issues.

The 1990s may revolutionize the care of the fetus and create new options in gene control, immunotherapy, and drug therapy not only to identify susceptible populations but to treat selectively that population without increasing the risk to the mother. Fetal therapy is a notable goal, even now somewhat within our grasp. No longer is the womb an isolated, forbidding environment, but it is accessible with such tools as magnetic resonance imaging, ultrasonography, CVS, Doppler, and sound clinical judgement. Current limitations in our understanding of the pharmacokinetics associated with these chemical temper our enthusiasm. The development of biomarkers for appropriate fetal drug therapy is to be encouraged, but also the development of fetal and maternal biomarkers that will assist the physician in actively avoiding inappropriate fetal drug therapy is necessary, whether dose or chemical dependent.

Biomarkers↗
PubMed1991

Graft length for anterior cruciate reconstruction.

We measured on the radiographs of 100 knees the length of the patellar ligament and the anterior cruciate ligament, and the distance between the tibial tubercle and the femoral insertion of the anterior cruciate. The length of the patellar ligament was always greater than that of the anterior cruciate ligament, but shorter than the distance between the tibial tubercle and the femoral insertion of the anterior cruciate by a mean of 14.2 mm (3 to 22). We conclude that anatomical, isometric replacement of the anterior cruciate is possible using a free graft, but not by the technique of retaining the tibial attachment originally described by Jones (1970).

Adolescent↗
PubMed1991

Using calcium chloride injection to improve tenderness of beef from mature cows.

The objective of this investigation was to determine the effect of calcium chloride (CaCl2) injection on Warner-Bratzler shear force (WBS), sensory panel ratings, and collagen traits of mature cow beef. Within 30 min of exsanguination, subprimals (top round, TR; top sirloin, TS; strip loin, SL) from alternate sides of the carcass were injected with a .3 M CaCl2 solution (10% of the subprimal weight) and aged for 1, 7, or 14 d. The corresponding cold-boned cuts of the other side served as a control. Injecting CaCl2 eliminated the requirement for extended postmortem storage, as indicated by d 1 WBS. During the 14-d aging period, WBS of noninjected cuts decreased by 2.59 kg, whereas WBS of CaCl2-injected samples decreased by only .35 kg. Compared with control cuts, CaCl2 injection improved (P less than .05) d-14 WBS of steaks from SL, TS, and TR by 41.1, 40.1, and 15.3%, respectively. Additionally, CaCl2-injected subprimals exhibited higher (P less than .05) sensory panel tenderness ratings, lower (P less than .05) amounts of detectable connective tissue, and shorter (P less than .05) sarcomere lengths. No differences (P greater than .05) were observed in any quantitative collagen traits between CaCl2-injected and control cuts. These results indicate that CaCl2 injection improved ultimate tenderness and sensory ratings of meat from mature cow cuts.

Age Factors↗
PubMed1991

National beef tenderness survey.

To determine the average tenderness and sensory ratings of beef subprimal cuts sold in retail cases across the United States, retail cuts were purchased through typical retail outlets in 14 metropolitan cities and transported to Texas A&M University for sensory and Warner-Bratzler shear analysis. The overall mean shear force for all cuts was 3.65 kg, and the mean shear force values for chuck, rib, loin, and round cuts were 3.72, 3.36, 3.17, and 4.31 kg, respectively. No difference (P greater than .05) in tenderness was detected among the cuts from the rib. Mean palatability ratings and shear force values of top loin steaks were similar to those of rib cuts. Top sirloin steaks were tougher (P less than .05) and received the lowest sensory ratings compared with other loin cuts. Approximately two to three times as many round and chuck steaks had shear force values in excess of 4.6 kg compared with their roast counterparts. In all cases, roasts tended to be more tender than steaks from the same subprimal source. USDA Choice chuck retail cuts, compared to Select and No-roll chuck cuts, had approximately 10% fewer cuts with shear force values in excess of 4.0 kg. More work is needed to improve meat tenderness, primarily for retail cuts from the round and chuck primals. Future research must investigate the interaction of antemortem and postmortem factors associated with variation in beef tenderness.

Animals↗
PubMed1990

Central nervous system lesions in the Wistar rat fetus following direct fetal injections of cadmium.

During embryogenesis, maternal administration of cadmium (Cd) produces teratogenic effects, including hydrocephalus (HC), whereas later in gestation (during the fetal period), such effects have not been reported. Since there is little placental transfer of Cd late in gestation, such differences in response could be due to a lower Cd concentration in the fetus compared with the embryo after maternal Cd exposure, or could be due to a decreased sensitivity of the fetal central nervous system (CNS) to Cd. To test the susceptibility of the late gestational CNS to Cd, day 19 (sperm plug = day 0) rat fetuses were directly injected i.p. with CdCl2 (165, 100, 50 nmoles/fetus in 5 microliters saline). All fetuses in one horn were treated with Cd, while fetuses in the other horn were treated with saline. Fetuses were collected on day 21, grossly examined, weighed, fixed in Bouin's fixative, and later razor sectioned. Cd did not affect fetal viability or body weight. However, Cd caused a dose-dependent increase in hydrocephalus, with the total number of fetuses showing moderate to severe HC being 0/45, 0/11, 6/10, and 18/20 for controls, low, medium, and high doses, respectively. Mild HC was noted in one control and two low Cd fetuses. Brain necrosis was correlated with hydrocephalus, being observed in 0/45, 0/11, 5/10, and 16/20 fetuses, respectively. In medium-dose fetuses without HC or brain necrosis, extravasation of erythrocytes was noted histologically within the cortical parenchyma, suggesting that hemorrhaging may lead to brain necrosis and hydrocephalus in Cd-exposed fetuses. Thus, the fetal CNS is susceptible to the toxic effects of Cd.

Animals↗
PubMed1990

Human endometrial cells grown on an extracellular matrix form simple columnar epithelia and glands.

Normal human endometrial cells were grown on an extracellular matrix containing type IV collagen, laminin, heparan sulfate proteoglycan, and entactin (Matrigel). On the extracellular matrix, dispersed endometrial cells remained rounded, and aggregated to form mounds of cells, which continued to grow in this arrangement. At 10 d, light microscopy demonstrated that these mounds were comprised of an eosinophilic substance, containing individual fusiform stromal cells. About 50% of the mounds were covered with a single layer of polarized cuboidal to columnar cells with basal nuclei, whereas 60% contained columnar cells forming glandular structures with open lumina. These polarized cuboidal and columnar cells were epithelial, based on their positive staining for cytokeratins and the possession of microvilli, tonofilaments, abundant glycogen, ribosomes, and primitive junctional complexes. Kreyberg's stain showed the presence of mucin within the lumina of the glands, indicating that they were functional. Thus, human endometrial cells grown on an extracellular matrix form a simple cuboidal to columnar epithelium, a stromal component, and glandular structures, thereby mimicking the in vivo morphology of the endometrium.

Cell Division↗
PubMed1990

Toxicity of cadmium in the perfused human placenta.

Cadmium, a placental toxicant in rodents, was studied in the in vitro isolated dually perfused human placental lobule for periods of up to 12 hr to determine if cadmium can also be toxic in the human placenta. Placental lobules were perfused with a modified M199 medium containing 0, 10, 20, or 100 nmol of cadmium chloride/ml added only initially to the maternal perfusate. Every 4 hr, the perfusates in both the maternal and the fetal circuits were replaced with fresh perfusate containing no Cd. Measurements during perfusion were oxygen consumption, net fetal oxygen transfer, fetal pressure, fetal volume loss, glucose utilization, lactate production, human chorionic gonadotropin (hCG), and zinc transfer. Postperfusion, morphology, and tissue slice studies were performed to evaluate cellular metabolic function and uptake of an amino acid (alpha-[14C]-aminoisobutyric acid). In all cadmium experiments, there were no significant alterations in oxygen consumption, lactate production, glucose utilization, or amino acid uptake compared with controls; however, there were dose-related changes in the synthesis and release of the protein hormone, hCG, beginning within 4 hr of initial exposure to Cd. There were also dose-related volume loss from the fetal vasculature (greater than 6 ml/hr) and ultrastructural changes (subsyncytiotrophoblastic vesiculations, stromal edema, vacuoles in Hofbauer cells), with necrosis at 100 nmol Cd/ml occurring between 5 and 8 hr. Cadmium (10 nmol/ml) reduced the placental transfer of zinc into the fetal circuit. Thus, the human placenta is a site for toxic action of cadmium and is at least as sensitive as the rodent placenta to the actions of cadmium. In addition, these human studies demonstrated a selectivity in the toxic effects with a maintenance of carbohydrate metabolism and amino acid uptake even after 12 hr of exposure with placental Cd burdens of 151 +/- 37 nmol/g, but with the earliest (within 4 hr) dose-related functional alterations occurring in protein hormone production and zinc transfer followed by later changes in morphology with a tissue Cd burden of 46.5 +/- 4.0 nmol/g.

Amino Acids↗
PubMed1989

Cadmium exposure on day 12 of gestation in the Wistar rat: distribution, uteroplacental blood flow, and fetal viability.

The effects of cadmium exposure (40 mumole CdCl2/kg, s.c.) on day 12 of gestation were evaluated in the Wistar rat. At 16-18 hours following such cadmium exposure, blood flow (as determined by radiolabeled microspheres) to the chorioallantoic placenta (CAP) was significantly reduced by 35%; at 24-26 hours, blood flow to the CAP had returned to control levels and was still unaffected at 38-43 hours. Uterine blood flow was not significantly altered at any of these timepoints. Between 16-18 and 24-26 hours after cadmium exposure, the concentration of cadmium in the placenta decreased significantly, while total cadmium content did not change. By 38-43 hours after cadmium exposure, total cadmium content of the placenta had increased significantly, although cadmium concentration was unchanged. There were no adverse effects on fetal viability or growth, as determined on day 20 of gestation. In sharp contrast, near-term (day 18) exposure to 40 or 50 mumole CdCl2/kg (s.c.) resulted in 53% and 82% mean incidences of fetolethality, respectively, within 24 hours. Administration of 50 mumole CdCl2/kg (sc) on day 12 also had no effect on fetal growth but resulted in increased fetolethality (12%). Thus midgestational cadmium exposure and its accompanying alterations in placental blood flow do not compromise fetal viability or growth. The differential response to cadmium at mid- and late gestation, in terms of fetolethality, is not due to maternal cadmium dose.

Animals↗
PubMed1989

Prenatal cocaine exposure to the fetus: a sheep model for cardiovascular evaluation.

Transplacental passage of cocaine in response to maternal administration of intravenous (IV) cocaine in doses of 1.0 and 2.0 mg/kg was studied in 6 pregnant ewes and fetuses and correlated with maximum changes in maternal and fetal blood pressures (BP), heart rates (HR) and fetal arterial blood gas values. Certain animals were given larger doses (3.0 and 5.0 mg/kg) of cocaine to examine cocaine-related cardiopulmonary and neurologic sequelae. Cocaine was extracted on C-18 sorbent columns and analyzed by gas chromatography. At 1.0 and 2.0 mg/kg, cocaine produced dose-dependent increases in maternal HR and BP which were maximum by 1 minute. The fetal response was characterized by maximum increases in BP and decreases in PO2 by 3 minutes and increases in HR by 15 minutes. Cocaine rapidly appeared in the fetal circulation, was approximately 15% of maternal concentrations by 5 minutes, and was undetectable in both circulations by 60 minutes. At cocaine doses of 3.0 and 5.0 mg/kg significant maternal cardiopulmonary and neurologic complications were encountered including bradyarrhythmias, respiratory distress, seizure and death. These data indicate that cocaine exerts direct drug actions upon maternal cardiovascular and neurologic function. In addition, cocaine affects fetal cardiovascular function directly via transplacental passage and indirectly by fetal hypoxemia from cocaine-induced uterine artery vasoconstriction. (NIDA 04415)

Animals↗
PubMed1988

Teratogenicity of tellurium dioxide: prenatal assessment.

The effects of multiple maternal subcutaneous injections of tellurium dioxide (TeO2) suspended in olive oil (0-1,000 mumol/kg) from day 15 to day 19 of gestation were evaluated in the Wistar rat. External and internal soft-tissue examinations were performed on day 20 fetuses. Multiple maternal injections, at doses higher than 10 mumol/kg, resulted in a dose-related appearance of hydrocephalus, edema, exophthalmia, ocular hemorrhage, umbilical hernia, undescended testis, and small kidneys in fetuses on day 20 of gestation. At 500 mumol/kg, reduction in maternal weight gain was also observed. At this level, the incidence of the above anomalies was 100%. The 100 mumol/kg dose of Te, which did not produce apparent maternal toxic responses, resulted in a 100% incidence of hydrocephalus and edema but no fetal mortality. Thus, tellurium can be teratogenic to the rat fetus without concomitant maternal toxicity. Also, the fetal period may be more sensitive than the organogenic period for the induction of hydrocephalus. Such evidence is consistent with the development of the choroid plexus and an effect of TeO2 on the production/resorption of cerebrospinal fluid.

Abnormalities, Drug-Induced↗