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Biomedical subjects

W H Miller

Publications and source records attributed to W H Miller.

At least 163 records · Page 9Linked to original sources
PubMed1990

Retinoic acid causes a decline in TGF-alpha expression, cloning efficiency, and tumorigenicity in a human embryonal cancer cell line.

The human teratocarcinoma NTERA-2 cl. D1 (NT2/D1) cell is a cloned multipotential embryonal cancer cell line that differentiates into a neuronal phenotype and other cellular lineages with retinoic acid (RA) treatment. Here we report that mRNA for the transforming growth factor-alpha is expressed in these RA-untreated cells and that RA-treatment results in a reduction of mRNA expression within 24 hr of treatment. In total cellular RNA, TGF-alpha mRNA is not detectable by Northern analysis at 6 days when there is increased expression of the human homeotic genes Hu-1 (Hox 2.1) and Hu-2 (Hox 2.2), known markers of RA response in NT2/D1 cells. RA treatment also causes a marked reduction in cloning efficiency and tumorigenicity of these cells. The addition of TGF-alpha or EGF (epidermal growth factor) protein to RA-untreated NT2/D1 cells augments soft agar cloning under limited fetal calf serum conditions. Blocking monoclonal antibodies directed against the EGF receptor (EGFr) can prevent this augmentation. We conclude that TGF-alpha expression inversely correlates with the state of RA-induced differentiation of this human teratocarcinoma cell and that TGF-alpha and EGF proteins are stimulatory growth factors in NT2/D1 cells under these culture conditions.

Cell Differentiation↗
PubMed1990

Black-hair follicular dysplasia in a Holstein cow.

A color-linked hypotrichosis was documented in an adult, black-and-white, Holstein cow. Skin biopsies from black-haired areas showed varying degrees of follicular dysplasia, while the white-haired areas were normal.

Alopecia↗
PubMed1989

Nutritional considerations in small animal dermatology.

Aside from food hypersensitivities, nutritional skin diseases in pets fed commercial foods appear to be very uncommon. Nutritional deficiencies all cause seborrheic skin signs and most of the clinical presentations are not pathognomonic for a specific nutrient deficiency. Careful consideration of the history and the results of skin biopsies usually suggest which nutrient is deficient. Because nutritional supplements can unbalance an animal's diet, they should not be used indiscriminately but only when indicated. Balanced nutrition should minimize the need for supplements.

Animals↗
PubMed1988

Rod light adaptation may be mediated by acceleration of the phosphodiesterase-guanylate cyclase cycle.

We compare the retinal rod photocurrent before and after introduction of an hydrolysis-resistant analog of GTP into the outer segment by the whole-cell patch technique. Others have shown that GTP bound to transducin leads to the hydrolysis of cyclic GMP, causing the response to light--a decrease in dark current. The hydrolysis-resistant GTP analog prolongs the response to a bright flash, which leads us to suggest that prolonged transducin activation by bright light desensitizes the rod by a prolonged decrease in dark current. Recovery from the response to a bright flash does occur after introduction of the analog; that recovery requires acceleration of cyclase activity rather than inhibition of phosphodiesterase. The analog mimics light adaptation by desensitizing the rod and speeding the recovery from a dim flash. The analog plus light or light adaptation prolongs the activities of transducin and phosphodiesterase (oligonucleate 5'-nucleotidohydrolase, EC 3.1.4.1) to mediate desensitization by reducing the dark current. Hence, this faster recovery from a dim flash would be by increased activity of guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] rather than by inhibited phosphodiesterase. Accelerated activity of guanylate cyclase may speed recovery by response truncation. We conclude that transducin, activated by photolyzed rhodopsin, may lead to increased activity of both phosphodiesterase and guanylate cyclase to mediate the desensitization and the faster recovery of the light-adapted response.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1988

Construction and operation of an open-circuit indirect calorimetry system for small ruminants.

An open-circuit indirect respiration calorimetry system for the collection of long-term metabolic heat production data for medium and small animals is described. The system is designed for use with small ruminants, but it has the capacity for measuring heat production in nonruminant species up to 150 kg. The system consists of an internal climatic control system, air flow control and volume measuring system, and gas analyzers for O2, CO2 and CH4. Carbon dioxide recovery checks of the four chambers produced recovery values ranging from 96.73 to 100.89%. The actual mean fasting heat production measured for 12 wether sheep was 63.13 kcal/kg.75 +/- .83. The total estimated cost of four chambers and the associated instrumentation was less than $17,000 in 1984.

Animal Husbandry↗
PubMed1987

Effector studies of 3'-azidothymidine nucleotides with human ribonucleotide reductase.

The 5'-mono-, di- and triphosphate derivatives (N3dTMP, N3dTDP and N3dTTP respectively) of 3'-azidothymidine (N3dThd), a new drug for the treatment of the acquired immune deficiency syndrome (AIDS), were synthesized. The abilities of these analog nucleotides to mimic the effector properties of the corresponding thymidine nucleotides with human ribonucleotide reductase were studied. Surprisingly, the mode of inhibition of CDP reduction by dTTP and dTDP was found to be competitive versus CDP. The Ki values were 22 and 78 microM respectively. Inhibition by N3dTTP and N3dTDP was considerably weaker, with Ki values of 1200 and 550 microM. Neither dTMP nor N3dTMP produced significant inhibition at concentrations up to 500 microM. dTTP was an essential activator for GDP reduction. In the presence of the accessory activator, ATP, the activation constant for dTTP was 7.8 microM. N3dTTP was neither an activator of GDP reduction nor an inhibitor of the activation by dTTP. In view of the intracellular concentrations of these analog nucleotides reached after incubations with N3dThd [Furman et al., Proc. natn. Acad. Sci. U.S.A. 83, 8333 (1986)] and the weakness of their interactions with ribonucleotide reductase, it is unlikely that the antiviral or toxic effects of N3dThd can be attributed to direct effects on this enzyme. The possible indirect effects caused by alterations in the pools of the natural effectors are discussed.

Antiviral Agents↗
PubMed1987

Antigiardial activity of guanine arabinoside. Mechanism studies.

Guanine arabinoside (araG) inhibited the in vitro growth of Giardia lamblia WB with an ED50 value of 4 microM. The inhibition was prevented completely by 2'-deoxyguanosine, prevented partially by guanine and guanosine, and not prevented by adenine, adenosine or 2'-deoxyadenosine. Extracts of G. lamblia grown in the presence of [8-3H]araG contained radiolabeled araGMP, araGDP and araGTP. The formation of araGTP during the exponential phase of cell growth increased with time and was dependent upon the araG concentration. AraG was incorporated into G. lamblia DNA in a time-dependent manner at a ratio of 1 araG for each 27 2'-deoxyguanosine residues. Short-term exposure of growing cultures to araG was inhibitory to DNA synthesis but not to RNA or protein synthesis. Over an extended period, synthesis of all three macromolecules was depressed. Attempts to measure araG phosphorylation by cell-free extracts of G. lamblia under a variety of nucleoside kinase and nucleoside phosphotransferase assay conditions were unsuccessful. In an attempt to understand further the action of araG, the metabolic pathways of guanine, guanosine and 2'-deoxyguanosine were delineated in detail. The presence of araG did not appear to cause any major alterations in the metabolism of these compounds; however, it was accompanied by a 3- to 4-fold increase in the endogenous pools of ATP and GTP.

Adenine↗
PubMed1987

The effect of 13-cis-retinoic acid on wound healing in dogs.

13-cis-retinoic acid is currently accepted as a valuable treatment for patients with severe nodulocystic acne. Many of these individuals express interest in surgical scar-correcting procedures. To ascertain the effect of 13-cis-retinoic acid on wound healing, sequential biopsies were examined from partial and full-thickness wounds in dogs following a 2-month course of retinoids. No significant difference was histologically observed from the control animal.

Animals↗
PubMed1987

3'-Azido-3'-deoxythymidine triphosphate as an inhibitor and substrate of purified human immunodeficiency virus reverse transcriptase.

Reverse transcriptase was purified from human immunodeficiency virus (HIV). It utilized the artificial primer-template poly(rA)-oligo(dT)12-18 more efficiently than activated calf thymus DNA, poly(rI)-oligo(dC)12-18, poly(rC)-oligo(dG)12-18, or poly(rCm)-oligo(dG)12-18. Maximum activity was observed at pH 7.0 to 7.6 in the presence of 5 mM MgCl2 and 100 mM KCl. 3'-Azido-3'-deoxythymidine triphosphate competed with dTTP for binding to HIV reverse transcriptase. Different kinetic constants were obtained with different primer-templates. Km and Ki values of 2.8 and 0.04 microM, respectively, were obtained with poly(rA)-oligo(dT)12-18. The corresponding values were 1.2 and 0.3 microM, respectively, with activated calf thymus DNA and 0.3 and 0.01 microM, respectively, with extracted virus and native template. Inhibition of the host cell DNA polymerases alpha and beta was considerably weaker. The Km and Ki values obtained with activated calf thymus DNA as the primer-template were 2.4 and 230 microM, respectively, for DNA polymerase alpha and 6.0 and 73 microM, respectively, for DNA polymerase beta. 3'-Azido-3'-deoxythymidine triphosphate could also serve as an alternate substrate for HIV reverse transcriptase. The resulting incorporation of 3'-azido-3'-deoxythymidine triphosphate into poly(rA)-oligo(dT)12-18 caused chain termination and premature deceleration of the reaction. The terminated primer could not be elongated when incubated with dTTP and HIV reverse transcriptase.

Anti-Bacterial Agents↗
PubMed1987

Does cone positional disorder limit resolution?

We measure the center-to-center spacings and disorder in spacings between all pairs of cones in a strip of primate retina extending from the foveal center to approximately 5.75 deg of retinal eccentricity along the temporal horizontal meridian. The strip is partitioned into windows, and the positions of the cone centers in each lattice window are digitized for analysis of lattice structure and quality. We find a nearly monotonic increase in cone spacing with eccentricity. The cone mosaic is a high-quality hexagonal lattice near the foveal center, and cone positional disorder (jitter) relative to averaging spacing increases beyond about 1.5 deg. We estimate human acuity measured through the optics of the eye over a retinal region comparable with our lattice strip by pooling the results of previous investigators. When the monkey lattice is scaled to human foveal resolution, application of the sampling theorem to average cone spacing predicts these pooled visual-acuity data from the foveal center to about 1.5 deg and overestimates visual acuity more eccentrically. Orientation reversal, a new technique developed by Coletta and Williams [J. Opt. Soc. Am. 4, 1503 (1987)] for estimating the Nyquist limit, estimates Nyquist frequencies from the foveal edge to beyond 5 deg of retinal eccentricity that agree with the cutoff frequencies predicted on the basis of our average spacing measurements. We conclude that the sampling theorem based on average spacing alone predicts the Nyquist limit from the foveal center to about 5 deg when that limit is measured by using the new aliasing technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Improved technique for closure of median sternotomy incision. Mersilene tapes versus standard wire closure.

A continuous series of 2,135 cardiac surgical procedures performed with a median sternotomy is reviewed. Standard closure with steel wire was used in 1,650 patients, and a new technique with Mersilene tape was used with 485. The rate of sternal dehiscence was 2.4% among those having wire closure, and there were no instances of dehiscence among the 485 patients with Mersilene tape closure (a statistically significant difference at p less than 0.005). The method was quick and easy to perform and highly effective in establishing firm and permanent approximation of the sternum. Presence of factors associated with increased risk of postoperative sternal dehiscence did not affect the outcome when Mersilene tape was used. We highly recommend this technique in all median sternotomy incisions.

Clinical Trials as Topic↗
PubMed1986

Frequency and antimicrobial susceptibility of Staphylococcus species isolated from canine pyodermas.

Specimens obtained from pyogenic skin lesions of 210 dogs were culturally examined for staphylococci. A total of 215 isolates of staphylococci were biotyped, using the biochemical tests contained in a commercial staphylococcal identification system. Of 201 coagulase-positive isolates, 197 were identified as Staphylococcus intermedius, 3 as S aureus, and 1 as S hyicus. Of 14 coagulase-negative isolates, 5 were identified as S epidermidis, 5 as S xylosus, 3 as S simulans, and 1 as S hominis. Antimicrobial susceptibility tests were done on all staphylococcal isolates, using the standard disk-diffusion method. Staphylococcus intermedius isolates were susceptible to cephalothin, methicillin, and gentamicin. Resistance to ampicillin, penicillin G, and tetracycline was frequent. Antibiotic resistance was not associated with the depth of skin infection. Resistance to ampicillin, penicillin, tetracycline, and trimethoprim-sulfamethoxazole was not associated with previous antibiotic use. Increased resistance to chloramphenicol, clindamycin, and erythromycin was associated with previous antibiotic therapy. Antimicrobial susceptibilities of the other Staphylococcus species isolated are reported, but the small numbers of these species precluded making meaningful comparison with S intermedius.

Animals↗
PubMed1985

Foregut cysts of the mediastinum. Results in 20 consecutive surgically treated cases.

Mediastinal cysts of foregut origin represent an important diagnostic group. Classified according to their anomalous embryonic origins, they include bronchogenic, esophageal, enteric, and nonspecific cysts. A series of 20 consecutive surgically treated cases from the thoracic surgical service of a large medical center is reported, all successfully resolved without mortality. Described are 12 bronchogenic, four enterogenous, and four nonspecific cysts, occurring in a variety of thoracic locations. Close attention to symptomatology reveals a wide range of manifestations, from total absence of symptoms to life-threatening respiratory distress. Definitive diagnosis was accomplished in some cases by means of noninvasive radiologic techniques, while angiography, bronchoscopy, and esophagoscopy were also useful in selected instances. Operative therapy consisted of complete excision if possible or partial excision if adhesion to intrathoracic bodies had occurred.

Adult↗
PubMed1985

Dietary and species influence on potential of plasma to stimulate differentiation and lipid accumulation in cultured adipocyte precursors.

Sera and plasma from different species and from rats of various dietary statuses were compared with regard to effects on proliferation, glycerophosphate dehydrogenase (GPDH) activity, and lipid-filing of rat adipocyte precursors converting to adipocytes in primary cell culture. All of the tested sera and plasma samples were comparably supportive of cell multiplication, but their effects on elevation of GPDH activity (a key event in adipocyte differentiation) and lipid-filling varied greatly. Plasma supported a much greater increase in GPDH activity than serum, while serum from cats supported a much lower increase than serum from humans, calves, goats, or rats. Dietary status of rats did not affect the potential of plasma to support GPDH activity, but did affect plasma support of lipid-filing. A higher than normal degree of lipid-filling was promoted by plasma from rats fed a high-fat, high-sugar diet, while a lower than normal degree was promoted by plasma from fasted rats. Lipid-filling was also found to vary in response to changes in content of very low density lipoprotein (VLDL) in human plasma. This suggests that the influence of diet on the potential of plasma to promote adipocyte lipid-filling may be mediated by the effect of diet on plasma VLDL. The absence of a diet-dependent effect of plasma either on multiplication of adipocyte precursors or on degree of elevation of GPDH activity leaves unresolved the mechanism by which diet affects adipocyte production in animals.

Adipose Tissue↗