Biomedical subjects

J E Miller

Publications and source records attributed to J E Miller.

At least 91 records · Page 5Linked to original sources

PubMed1994

Development of the cerebellar defect in ataxic SELH/Bc mice.

In SELH/Bc mice, 5-10% of young adults are ataxic, due to a midline cleft in the cerebellum. An additional 10-20% of SELH/Bc embryos have exencephaly and die at birth. All SELH/Bc embryos omit a normal step in cranial neural tube closure, initiation of fusion at Closure 2. In the 80-90% that complete cranial neural tube closure, the last region of closure, on late D9, is the region of the prospective cerebellum, and its closure is late. We postulated that the cleft cerebellum in ataxic SELH/Bc mice derives from this delay in neural tube closure and predicted that we would see evidence of a cerebellar midline cleft in all earlier stages after cranial neural tube closure is normally complete. In the present study we show that the cerebellum is cleft in a 7-9% proportion of SELH/Bc D16 fetuses (2/28) and D11 embryos (15/167), and that the defect is detectable on D10. In these abnormal D16 fetuses, D11 and D10 embryos, there is a gap in midline continuity of cerebellar neuroepithelium, a finding consistent with our hypothesis that the neuroepithelium in this region fails to complete fusion in those embryos. We also show that cerebella of adult SELH/Bc ataxic mice have no obvious deficiency of lobules, or disorganization of tissue as in the Wnt-1 mutants.

Animals↗

PubMed1994

Ivermectin resistant Haemonchus contortus in Louisiana lambs.

Fifteen weaned crossbred (Suffolk x Louisiana Native) lambs were treated with albendazole (10 mg kg-1) to remove existing nematode infections. They were inoculated with Haemonchus contortus infective larvae from a residual population surviving treatment with the oral formulation of ivermectin (0.2 mg kg-1). One group of five lambs remained untreated, another group of five was treated with the injectable formulation of ivermectin (0.2 mg kg-1), and a third group of five was treated with the oral formulation of ivermectin (0.2 mg kg-1). Subsequent to the treatments, there was essentially no difference in mean fecal egg count or mean number of H. contortus recovered at necropsy between the three groups.

Albendazole↗

PubMed1994

Validation of a flow cytometric in vitro DNA repair (UDS) assay in rat hepatocytes.

An in vitro flow cytometric (FCM) DNA repair assay has been developed and validated by comparison to conventional autoradiography (ARG). Both assays measure unscheduled DNA synthesis (UDS). Cultures of hepatocytes from young male Sprague-Dawley rats were exposed to a battery of 26 chemicals plus bromodeoxyuridine (BrdUrd) or 3H-thymidine (3H-dT) for 18-20 h before harvest. Selection of test chemicals was based upon both their genotoxicity classifications and carcinogenicity bioassay results in male rats. DNA repair in chemically treated cultures was detected flow cytometrically by measuring the uptake of BrdUrd in non-replicating (G1, G2, mitotic and 4C) cells. Intracellular levels of incorporated BrdUrd were visualized by immunochemical labeling with fluorescein isothiocyanate (FITC), and total cellular DNA content was simultaneously estimated by counterstaining samples with the nucleic acid intercalator, propidium iodide (PI). Information was obtained from 10(4) cells/sample. Since repairing cells incorporate significantly less BrdUrd per unit of time than replicating cells, low intensity BrdUrd-FITC fluorescent signals from repairing cells are readily discriminated from high intensity signals from replicating cells when displayed on linear univariate histograms. Further distinction between repairing and replicating cells was achieved by displaying the DNA contents of all cells on linear bivariate histograms. Thus, repairing cells were resolved without subjecting these cultures to agents which suppress replicative synthesis (e.g., hydroxyurea). Results from these concurrent FCM and ARG investigations include the following: (1) conclusions (DNA repair positive or negative) were in agreement, with one exception, cinnamyl anthranilate, for which cytotoxic doses produced a positive FCM response, but lack of intact hepatocytes in parallel ARG preparations prevented analysis; (2) similar sensitivities for most of the positive chemicals were reported; (3) a high correlation (85%) exists between the reported genotoxicity classification and these DNA repair results in the absence of overt cytotoxicity; (4) a poor correlation exists between these DNA repair results and hepatocarcinogenesis (only 4/11 liver carcinogens tested positive) or overall carcinogenesis in the male rat (only 9/21 carcinogens tested positive). This FCM assay provides a rapid, sensitive, safe and reliable means of identifying agents which induce DNA repair in mammalian cells.

Animals↗

PubMed1994

Birth order, interpregnancy interval and birth outcomes among Filipino infants.

This study examines the effects of birth order and interpregnancy interval on birthweight, gestational age, weight-for-gestational age, infant length, and weight-for-length in a sample of 2063 births from a longitudinal study in the Philippines. First births are the most disadvantaged of any birth order/spacing group. The risks associated with short intervals (< 6 months) and high birth order (fifth or higher) are confined to infants who have both attributes; there is no excess risk associated with short previous intervals among lower-order infants, nor for high birth order infants conceived after longer intervals. This pattern is observed for all five birth outcomes and neonatal mortality, and persists in models that control for mother's age, education, smoking, family health history and nutritional status. Since fewer than 2% of births are both short interval and high birth order, the potential reduction in the incidence of low birthweight or neonatal mortality from avoiding this category of high-risk births is quite small (1-2%).

Adult↗

PubMed1994

Behavioral response of host-seeking mosquitoes (Diptera: Culicidae) to insecticide-impregnated bed netting: a new approach to insecticide bioassays.

The response of Anopheles gambiae Giles s.s and Culex quinquefasciatus Say to insecticide-treated netting in a wind tunnel permeated with guinea pig odors was recorded on videotape. With no insecticide present, mosquitoes spent 99% of the time on the netting, either at rest or occasionally walking across it. On nylon netting, permethrin at 50, 400, and 1,000 mg m-2 irritated the mosquitoes, causing them to spend significantly more time away from the netting and relatively more time walking than at rest when they were on the netting. These effects increased with dose, but the total contact time was always enough to cause 100% mortality. At the two highest doses, knockdown occurred before the end of the 10-min observation period. A wash-resistant formulation of permethrin (ICI patent) reduced irritancy without affecting mortality or knockdown. A mixture of pirimiphos-methyl and permethrin also was less irritating than permethrin alone. Pirimiphos-methyl at 400 mg m-2 was the least irritating of all treatments tested. Lambda-cyhalothrin at 2.5, 6, and 25 mg m-2 was less irritating than permethrin, even though the doses of lambda-cyhalothrin used were far more toxic than the permethrin doses as measured by LT50. Cotton netting significantly reduced the toxicity and irritancy of the permethrin treatments. Cx. quinquefasciatus was less irritated by permethrin but more irritated by lambda-cyhalothrin, than was An. gambiae. Our study indicated that mosquitoes are so strongly attracted to a host protected by netting, they will tolerate relatively high doses of irritating insecticides long enough to pick up lethal doses.

Animals↗

PubMed1994

A superfamily of S locus-related sequences in Arabidopsis: diverse structures and expression patterns.

Six sequences that are closely related to the S gene family of the largely self-incompatible Brassica species have been identified in self-fertilizing Arabidopsis. The sequences define four genomic regions that map to chromosomes 1 and 3. Of the four functional genes identified, only the previously reported Arabidopsis AtS1 gene was expressed specifically in papillar cells and may function in pollination. The remaining three genes, including two novel genes designated ARK2 and ARK3, encode putative receptor-like serine/threonine protein kinases that are expressed predominantly in vegetative tissues. ARK2 promoter activity was detected exclusively in above-ground tissues, specifically in cotyledons, leaves, and sepals, in correlation with the maturation of these structures. ARK3 promoter activity was detected in roots as well as above-ground tissues but was limited to small groups of cells in the root-hypocotyl transition zone and at the base of lateral roots, axillary buds, and pedicels. The nonoverlapping patterns of expression of the ARK genes and the divergence of their sequences, particularly in their predicted extracellular domains, suggest that these genes perform nonredundant functions in specific aspects of development or growth of the plant body.

Amino Acid Sequence↗

PubMed1994

Characterization of 24-h cortisol release in obese and non-obese hyperandrogenic women.

Excessive androgen output is a well-recognized feature of adrenocortical oversecretion in women with ovarian hyperandrogenism, or polycystic ovary disease (PCOD). However, evidence of a concomitant alteration of cortisol secretion is lacking even though obesity per se, a common clinical feature of PCOD, has been shown to be associated with cortisol oversecretion. To clarify whether a subtle alteration in cortisol secretion exists, a study of 24-h episodic cortisol release and post-prandial cortisol responses was undertaken in eight women with PCOD and eight normal women comprising equal numbers of obese and non-obese subjects. All four groups showed normal biphasic 24-h cortisol secretion profiles but cortisol pulse frequency was increased in the PCOD groups. Independently, both hyperandrogenism and obesity were associated with an accelerated cortisol clearance rate. These changes, together with normal or only slightly elevated 24-h cortisol integrated area under the curve, suggest an increased compensatory cortisol production in women with PCOD. Furthermore, subjects with PCOD and subjects with obesity showed different post-prandial cortisol responses to normal non-obese women. In conclusion, these subtle cortisol abnormalities may be a manifestation of altered central regulation of the hypothalamic-pituitary-adrenal axis and peripheral metabolic abnormalities, and may be linked to the pathophysiology of PCOD.

Adult↗

PubMed1993

Statistical confirmation that immunofluorescent detection of DNA repair in human fibroblasts by measurement of bromodeoxyuridine incorporation is stoichiometric and sensitive.

Diploid human fibroblasts (IMR-90 cells), grown to confluency and growth-arrested by serum starvation, were irradiated with a variety of doses of UV light (0.025-40 J/m2) or incubated with broad dose ranges of four direct-acting mutagens [ethyl methanesulfonate (EMS), ICR-170, methyl methanesulfonate (MMS), and 4-nitroquinoline oxide (4-NQO)] and pulsed with a thymidine analog, 5-bromodeoxyuridine (BrdUrd) to detect evidence of DNA repair. These cells and appropriate controls were immunochemically stained and subjected to flow cytometric analysis to quantify BrdUrd incorporation into DNA and simultaneously measure cellular DNA content. Since the maximal quantity of BrdUrd incorporated with repairing cells is profoundly less than the amount incorporated during replicative synthesis and flow cytometric analysis collects information on a cell-to-cell basis, data collection using linear histograms succeeded both in revealing repairing cellular populations and eliminating replicative cells from the analysis. Technical modifications necessary to achieve stoichiometry with UV-irradiated IMR-90 fibroblasts included a 48h repair (and pulse) period, followed by denaturing cellular DNA for 15 min at 90 degrees C. The limit of detection was equal to or below the lowest dose investigated (0.025 J/m2). DNA repair was also detected with cultures incubated with low doses of all chemicals and pulsed with BrdUrd for a 24 h period. The limits of detection were near or below 500 microM EMS, 5 microM MMS, 0.25 microM 4-NQO, and 0.1 microM ICR-170.

Bromodeoxyuridine↗

PubMed1993

Ataxia and a cerebellar defect in the exencephaly-prone SELH/Bc mouse stock.

SELH/Bc inbred mice have an abnormal mechanism of anterior neural tube closure and 10-20% of embryos have a lethal neural tube closure defect, exencephaly. Our previous studies have focused on this multifactorial threshold trait. However, SELH mice are also characterized by another trait that also shows non-Mendelian transmission ratios, an ataxia recognized in juvenile and adult mice. Here we report our first genetic and morphological studies of the ataxia trait. Recent pedigree records for the SELH colony showed that 7% of the 467 weaned progeny from normal breeding pairs were ataxic; 17 of the 20 pairs produced ataxic progeny. This result was statistically consistent with the hypothesis that all SELH mice have the ataxic genotype, which is expressed in only 7% of them. Genetic studies of an outcross to a normal strain and the subsequent F2 and testcross of the F2 were also done. The results were consistent with a one or two gene locus cause of liability to ataxia in SELH mice. The genetic correlation between exencephaly production and ataxia production for a sample of nine F2 males was 0.35, as expected if both traits are caused by the same genes, but was not statistically significant. In another approach, we examined the morphology of brains from normal and ataxic adult SELH mice. All 20 brains from non-ataxic SELH mice were morphologically normal. In all 18 brains from ataxic SELH mice the cerebellum was abnormal, lacking the vermis, and characterized by a midline fissure. This phenotype in mice has previously been known in Mendelian mutants at the Wnt-1 locus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Histological study of the cranial neural folds of mice genetically liable to exencephaly.

The SELH/Bc (SELH) inbred stock of mice has a high liability to the neural tube closure defect, exencephaly. All SELH embryos close their cranial neural tubes by an abnormal mechanism, lacking elevation and initiation of fusion in the posterior prosencephalon/anterior mesencephalon region. Most embryos complete closure of the cranial neural tube by extension of a more rostral site of fusion, but in 10-20% this process fails, and the embryos are subsequently exencephalic. In this study, transverse histological sections of the cranial neural folds of SELH embryos at the 3-5, 6-8, and 9-11 somite stages were compared to those of two strains with normal neural tube closure, ICR/Bc and LM/Bc. At all stages, consistent morphological differences were observed between SELH and the two normal strains. In 3-5 somite SELH embryos, the divergence of the folds from the neural groove is more angular, the folds are flatter, and their lateral tips appear "hooked" downward. In 6-8 somite SELH embryos, the lateral tips of the folds appear more elongated and in the prosencephalon they are less elevated than in the normal strains. The boundary between neuroepithelium and mesenchyme or surface ectoderm tends to be less clear than normal in SELH lateral tips. In 9-11 somite SELH embryos, divergence of the folds from the neural groove continues to be angular and the lateral folds are splayed horizontally. In addition, the lateral surface ectoderm is abnormally indented and the neuroepithelium/surface ectoderm boundary is more ventral and lateral in SELH than in ICR/Bc and LM/Bc. The hypothesis that the defect in SELH cranial neural folds might involve the cytoskeleton was tested using a fluorescent probe for filamentous actin in 7 somite SELH and ICR/Bc embryos. The actin staining pattern in SELH embryos was like that of normal ICR/Bc embryos, with a strongly staining apical concentration in the neuroepithelium. This suggests that there is no gross cytological abnormality within the neuroepithelium, but does not rule out more subtle defects, such as those involving cytoskeletal function.

Animals↗

PubMed1993

Model analysis of interactive effects of ozone and water stress on the yield of soybean.

The interactive effects of ozone and water stress on the yield of soybean (Glycine max (L.) Merr. 'Davis') were addressed with a growth model of soybean. Two simulations were conducted, using the data from the exposures of soybean to ozone in open-top chambers under two soil moisture regimes, and the results of the simulations were compared. In the original simulation, soil moisture content was calculated based on a water budget using the actual precipitation and irrigation data. In the modified simulation, the soil water content was given as input data. In this case, soil moisture content was maintained at the same level across the ozone treatments regardless of different water use by the plants. Both simulations included the effect of reduced ozone flux to the leaves due to water stress, whereas only the original simulation included the effect of mitigated water stress due to reduced water use by the plants under higher ozone concentration. The water stress reduced ozone impact on soybean yield in the original simulation on the basis of the ozone dosecrop yield response relationship, but not in the modified simulation. The ozone uptake rate was reduced by water stress in the original simulation, but the relationship between seasonal mean ozone uptake rate and relative yield still showed reduced impact of ozone due to water stress. These results indicated that the alleviation of water stress by ozone due to reduced plant water use in ozone-treated plots can be a contributing factor in the reduction of ozone impact by water stress. The above conclusion was partly confirmed by the actual data for soil water content, which was significantly lower in the lowest ozone treatment than in the higher ozone treatments. Further experimental and modelling studies are needed to elucidate the mechanism of the ozone X water stress interaction.

Journal Article↗

PubMed1993

Observations on nematode parasitism in cow-calf production systems in southcentral/southwestern USA.

Observations on fecal egg count (FEC) and nematode identification data were compiled to help determine the extent of nematode parasitism in cows and their nursing calves. Overall mean FEC values for cows in Utah, Louisiana, Nevada, Texas, and California were 7 eggs per gram (EPG), 6 EPG, 9 EPG, 10 EPG, and 15 EPG, respectively. Overall mean FEC values for nursing calves from the same states were 7 EPG, 228 EPG, 3 EPG, 60 EPG, and 398 EPG, respectively. The overall mean FEC value for Arizona cows was 33 EPG. Relatively complete seasonal FEC data were available from California and Louisiana where fall-born calves acquired high nematode burdens (i.e. 400-500 EPG) as early as 3 months of age, and spring-born calf FEC started low (10-30 EPG) and reached high levels (200-400 EPG) at about 5 months of age. In California, tracer calf data indicated that Ostertagia and Cooperia were the predominant nematodes acquired from pasture. In Louisiana, tracer calf, tracer cow, slaughtered calf (at weaning) and coproculture data indicated that Ostertagia (fall/winter) and Haemonchus (summer/fall) were the predominant nematode genera acquired by cows and that Ostertagia (winter/spring), Haemonchus (summer) and Cooperia (all seasons) were the predominant nematode genera acquired by calves. The acquisition of nematodes in tracer cows was much lower than in calves; however, the percentage of inhibited Ostertagia (ranging from 0% in summer to more than 80% in spring) was similar. A survey of abomasal nematodes in culled dairy and beef cows in Louisiana indicated that cows can harbor large (mean of 24,543 for beef and 16,383 for dairy) burdens.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Husbandry↗

PubMed1993

Mechanical compatibility of noncemented hip prostheses with the human femur.

It is generally accepted that more flexible implants are needed to reduce stress shielding and postoperative thigh pain. However, there is no detailed information on the stiffness of currently used implants relative to the human femur. The purpose of this study was to determine the stiffness characteristics (bending, torsional, and axial) of human femora relative to commercially available prostheses as a first step in assessing the mechanical compatibility of the implants. This was achieved by computerized tomography scanning of a collection of human femora from proximal to distal at 10 mm intervals, digitizing the cross-sectional contours, and calculating the stiffness characteristics of each section using standard beam theory. The results show that significant stiffness mismatches exist, especially for larger stem sizes and for stems fabricated from cobalt-chrome alloy. Interestingly, certain implant stiffness values are lower than those of the femur for stems up to 15 mm in diameter, substantially so if the implant is made from titanium alloy and incorporates design features that reduce area and moments of inertia. The data suggest that only larger implant sizes need to be adjusted for increased flexibility compared with current stands.

Aged↗

PubMed1993

Variation in attractiveness of human subjects to malaria mosquitoes (Diptera: Culicidae) in The Gambia.

During experimental hut trials to assess the efficacy of insecticide-treated bednets against malaria mosquitoes, we observed that human subjects varied consistently in their attractiveness to mosquitoes. Attractiveness was assessed by estimating the numbers of wild Anopheles gambiae Giles mosquitoes entering a hut in which a man was sleeping, and the numbers of human-bloodfed An. gambiae sensu lato collected from each hut each morning. Five trials were carried out at Wali Kunda in rural Gambia during 2.5 yr. During each 6-wk trial a man slept under a bednet in each of the six huts. Morning collections of mosquitoes from the room, enclosed verandas, and window traps of each hut provided estimates of the number of mosquitoes that had entered during the night. Blood meals were analyzed using an ELISA technique to identify those mosquitoes feeding on humans. Specimens were collected by field workers, not the subjects; therefore, sampling was independent of the subjects' ability to catch mosquitoes. Moreover, the trials were designed to measure the relative attractiveness of individual sleepers to mosquitoes, allowing for other sources of variation (i.e., among huts, bednets, nights, and day of the week). Attractiveness of men to mosquitoes differed significantly among individuals as indicated by the consistent differences between the numbers of mosquitoes entering each man's hut and the numbers feeding on each man. However, the two measures of attractiveness were apparently independent of each other: subjects who attracted consistently high numbers of vectors into their hut did not necessarily have high numbers of mosquitoes feeding on them. These findings support the view that some individuals within a community are at greater risk from mosquito-borne pathogens than others.

Adult↗

PubMed1993

PTCA failure.

Explore the source record for details and available documents.

Angioplasty, Balloon, Coronary↗

PubMed1993

IgG antibodies from patients with bullous pemphigoid bind to fusion proteins encoded by BPAg1 cDNA.

Bullous pemphigoid (BP) is an autoimmune blistering skin disease characterized in part by the presence of circulating and tissue-bound IgG antibodies directed against the epidermal basement membrane zone. IgG from over 95% of patients with BP have been shown to immunoprecipitate a 230-kD epidermal protein, BPAg1, which has been cloned and sequenced. Although sera from almost all patients with BP react with the 230-kD BP antigen the specific epitope(s) of BPAg1 that IgG binds is not known. We have generated fusion proteins from the 230-kD BP antigen cDNA and analyzed sera from patients with BP for binding to these fusion proteins by immunoblot. Sera from 21 of 30 (70%) patients with BP reacted with FP3A (amino acid 873-1193) compared to four of 13 (30%) normal subjects (p < 0.02). Sera from 10 of 30 (33%) patients reacted with FP7 (AA1623-1812) and to FP3 (AA1003-1193), compared to one of 22 (5%) and 0 of 19 (0%) controls, respectively. No significant reactivity was noted against two other fusion proteins (FP6, FP9). Twenty-four of 30 (80%) patients with BP reacted to at least one of three fusion proteins (FP3, FP3A, FP7) compared to three of 11 (27%) of the control subjects (p < 0.003). Fusion proteins FP3, FP3A, and FP7 are at the amino- or carboxyl-terminal regions of the putative central alpha-helical coiled-coil rod domain of BPAg1, which has been postulated to be involved in the self-aggregation of BPAg1. These findings demonstrate that patients with bullous pemphigoid react with multiple regions of BPAg1 and suggest that part of the pathologic consequences of these auto-antibodies in patients with bullous pemphigoid may be by the disruption of the normal self-aggregation of the BPAg1.

Animals↗

PubMed1993

Reestablishment of lymphatic drainage after canine lung transplantation.

The technique of pulmonary lymphoscintigraphy was used to evaluate pulmonary lymphatic flow and to assess reestablishment of lymphatic drainage after lung transplantation. A first group of six control dogs underwent percutaneous transthoracic injection of a radiocolloid into the periphery of the left upper and lower lobes. Radiocolloids are large molecules tagged with radioisotopes that are absorbed only through lymph and are concentrated in tributary lymph nodes. Twenty-four hours after injection the dogs underwent scintigraphic studies of the chest and upper part of the abdomen. Mediastinal lymph nodes were visualized in all animals. A second group of four dogs underwent partial reimplantation of the native left lung, with interruption of all lymphatic connections between the lung and mediastinum. Lymphoscintigraphic studies of the left lung were obtained on the third postoperative day and then weekly for 4 weeks. Three of the four dogs in this group did not have visible mediastinal nodes 3 days after the operation. Nodes were visualized in all animals at 1 week and at all following studies. A third group of five dogs were subjected to left lung allotransplantation by means of standard surgical techniques, as well as immunosuppression. The animals were studied with radiocolloid injections and lung lymphoscintigraphy at weekly intervals for 6 weeks. Mediastinal nodes were visualized for the first time 2 to 4 weeks after the operation and at every subsequent study. We conclude that lung lymphoscintigraphy is a reliable technique for the study of pulmonary lymphatic flow. This experiment demonstrates that lymphatic drainage after lung transplantation is reestablished as early as the second postoperative week.

Animals↗

PubMed1992

Evaluation of ivermectin against experimental infections of Haemonchus contortus and Trichostrongylus colubriformis in goats.

Fourteen nematode parasite-naïve kids were given a mixed larval inoculum (approximately 17,250 infective larvae) via stomach tube. Twenty-two days after infection, the kids were randomly assigned to control and treatment groups of seven animals each. Mean eggs per gram for control and treatment groups were 4304 and 5315, respectively. Kids in the treatment group were given ivermectin (0.2 mg kg-1) administered by subcutaneous injection. At necropsy, the mean numbers of Haemonchus contortus and Trichostrongylus colubriformis for control and treatment groups were 2259 and 0, and 3033 and 773, respectively. This reduction was significant (P less than 0.05) for both species, resulting in an efficacy of 100.0% and 74.5%, respectively. The lower efficacy against T. colubriformis may be a sign of resistance, a reduced effectiveness due to route of administration, or a higher dose may be required with subcutaneous administration, as has been observed previously.

Animals↗