Biomedical subjects

M W Miller

Publications and source records attributed to M W Miller.

At least 181 records · Page 10Linked to original sources

PubMed1993

Requirement of inner cell mass for efficient chorionic gonadotrophin secretion by blastocysts of common marmosets (Callithrix jacchus).

The role of the inner cell mass in the induction of chorionic gonadotrophin synthesis and secretion by the trophoblast of the peri-implantation primate blastocyst was studied in common marmoset monkeys. An in vitro system for the culture of blastocysts commencing with blastocysts collected 8 days after conception was developed. Chorionic gonadotrophin measured in the spent culture fluid was first detected in most blastocysts after 3 or 4 days (day 11 or 12) of culture at a time equivalent to implantation in vitro. Initial secretion of chorionic gonadotrophin coincided with development of parietal endoderm and histological appearance of syncytiotrophoblast in the polar trophoblast. Little chorionic gonadotrophin was secreted by blastocysts with a poorly developed, or absent, inner cell mass. Mural trophoblast removed from blastocysts after 2 days of culture (day 10) grew in vitro as a unilaminar vesicle but failed to secrete significant amounts of chorionic gonadotrophin. However, mural trophoblast from older blastocysts (days 13 and 14) after chorionic gonadotrophin secretion had commenced continued to secrete chorionic gonadotrophin, with trophoblast from day 14 blastocysts secreting significantly more than that from day 13. It was concluded from these studies that while mural trophoblast from marmoset blastocysts will proliferate in vitro in the absence of an inner cell mass, efficient induction of chorionic gonadotrophin secretion requires the presence of the inner cell mass or its derivatives. Once chorionic gonadotrophin secretion has commenced, secretion will continue in the absence of the inner cell mass.

Animals↗

PubMed1993

The buccalin-related neuropeptides: isolation and characterization of an Aplysia cDNA clone encoding a family of peptide cotransmitters.

The buccalin-related peptides, buccalin A and buccalin B, are members of a family of cotransmitters that modulate neuromuscular transmission in Aplysia. In this study, a third buccalin-related peptide, buccalin C, was purified from neuronal elements in the accessory radula closer, a muscle involved in the animal's feeding behavior. Oligonucleotide probes based upon the amino acid sequence of buccalin C were used to isolate cDNA clones that encode a buccalin precursor polypeptide. The buccalin precursor contains 19 distinct buccalin-related peptides, several of which are present in multiple copies. The buccalin gene appears to be present in a single copy, with one allele containing a small insert. Expression of this gene occurs in a tissue-specific manner and mRNA transcripts are abundant within neurons in the Aplysia CNS. This large family of neuropeptides may exert extraordinarily complex modulatory actions at synapses where they serve as cotransmitters.

Amino Acid Sequence↗

PubMed1993

Longitudinal study of in vitro CD4+ T helper cell function in recently transplanted renal allograft patients undergoing tapering of their immunosuppressive drugs.

Three distinct T helper activation pathways contribute to interleukin-2 production by human peripheral blood mononuclear cells following in vitro stimulation with HLA alloantigens in a mixed lymphocyte reaction. These pathways involve both CD4+ and CD8+ T helper cells, as well as self and allogeneic antigen-presenting cells. The pathways are differentially susceptible to cyclosporine in vitro, with the CD4+ T helper cell and selfAPC (CD4 approximately sAPC) pathway being the most sensitive. Furthermore, these pathways are differentially susceptible to immunosuppressive drugs in renal allograft patients, and by functional analysis of these pathways we have identified patients who are at increased risk for rejection of their kidney allografts. The present report provides a longitudinal study of the functional T helper cell status of recently transplanted renal allograft recipients undergoing tapering of their immunosuppressive drugs by testing the ability of recipient PBMC to generate IL-2 in response to pathway-specific stimuli. This study provides evidence that IL-2 generation by T helper pathways is dynamic, fluctuating independently of the commonly followed clinical parameters used to assess graft function and degree of immunosuppression. Significantly, the function of the CD4 approximately sAPC activation pathway correlates with risk of acute rejection. As such, we suggest that periodic assessment of pathway specific T helper function is a more sensitive index for the detection of subtherapeutic dosing of immunosuppressives--and, in particular, for assessing cyclosporine maintenance requirements. Monitoring of pathway specific activity with appropriate cyclosporine dosing adjustments might prevent the initiation of the rejection process and reduce a major source of late graft failure.

Adult↗

PubMed1993

The myomodulin-related neuropeptides: characterization of a gene encoding a family of peptide cotransmitters in Aplysia.

The myomodulin-related peptides comprise a family of cotransmitters that modulate neuromuscular signaling in the feeding system of Aplysia. In this study, cDNA clones encoding a myomodulin precursor polypeptide were isolated and characterized. This precursor contains seven different myomodulin-related peptides, one of which, myomodulin A, is present in 10 contiguous copies. The sequence of a myomodulin genomic clone indicates that all of these myomodulin-related peptides are encoded on a single exon. The myomodulin gene is expressed in a tissue-specific manner and myomodulin mRNA is localized to specific neurons in the Aplysia CNS. The presence of multiple related neuropeptides can greatly increase the range and precision of signaling at synapses where they act as modulator cotransmitters.

Amino Acid Sequence↗

PubMed1992

3H-uridine uptake in human leukemia HL-60 cells exposed to extremely low frequency electromagnetic fields.

Human leukemia HL-60 cells in vitro were exposed or sham-exposed to a 60 Hz electric (3.40 mV/m) or magnetic 10 G (1 muT) field for 5 hr in an attempt to replicate the results of a previously published report (1) of increased uptake of [3H] uridine in response to similar exposure conditions. The results of the present experiments indicated no treatment effect of the fields on uridine incorporation. The ability to detect differences in [3H] uridine uptake were confirmed in a negative control experiment. A 'negative control' experiment demonstrated a statistically significant increase in 3H-uridine uptake for cells at 37 degrees C relative to those at 4 degrees C.

Biological Transport↗

PubMed1992

Clinical, echocardiographic, and Doppler imaging characteristics of mitral valve stenosis in two dogs.

Mitral stenosis was diagnosed noninvasively by echocardiography and Doppler imaging in 2 Bull Terriers. Two-dimensional echocardiography revealed severe atrial and moderate left ventricular dilatation; severely reduced mitral valve opening excursion; doming of the cranial mitral valve leaflet into the left ventricle during diastole; thickened, nodular cranial mitral valve leaflets; and reduced mitral valve orifice. M-mode echocardiographic findings additionally indicated greatly diminished mitral valve E to F slope and abnormal caudal mitral valve leaflet motion. Color flow Doppler imaging revealed bright bursts of color with aliasing originating from the stenotic mitral valve orifice, extending into the left atrium during systole, and into the left atrium during diastole. Spectral Doppler recordings revealed transvalvular mitral valve gradients and prolonged pressure half-times. Necropsy performed on 1 dog revealed extremely thickened, nodular, and stiff mitral valves with short, thickened, and fused chordae tendineae. The diagnosis of mitral valve stenosis was easily facilitated with diagnostic ultrasonography.

Animals↗

PubMed1992

Circadian rhythm of cell proliferation in the telencephalic ventricular zone: effect of in utero exposure to ethanol.

The neocortical ventricular zone is composed of a desynchronized population of proliferating cells. These cells give rise to neurons in the infragranular laminae of neocortex. The present study documents a diurnal rhythmicity of cell proliferation in the ventricular zone and examines the effects of ethanol on this biological clock. Pregnant rats were fed one of 3 diets. They were provided an ethanol-containing (6.7% v/v) liquid diet ad libitum between gestational day (G) 6 and G18, pair-fed an isocaloric liquid control diet, or fed chow and water. Throughout the experiments, the rats were fed either at 08.00 h (E.S.T) or at 17.00 h (lights on 06.00 to 18.00 h). Rats were given a single injection of bromodeoxyuridine (BrdU) on G17 at one point during a 24 h period (03.00, 06.00, 09.00 h, etc.). The fraction of ventricular cells that incorporated the BrdU was determined using quantitative immunohistochemical methods. Pair-fed control rats (fed at 08.00 or 17.00 h) consumed their food within 4 h of presentation. The ratio of cells passing through the S-phase of the cell cycle changed diurnally; the ratio was highest during the day (0.52 +/- 0.01 at 12.00 h) and lowest during the night (0.40 +/- 0.02 at 03.00 h). In contrast, the ethanol-fed rats grazed on their food throughout the dark cycle regardless of when the food was presented. The mean peak blood ethanol concentration was 142 +/- 13 mg/dl during the dark phase and less than 25 mg/dl during the light phase. Prenatal exposure to ethanol eliminates the fetal circadian rhythm in cell proliferation (mean labeling index of 0.45 +/- 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Severe bilateral fibrosing pleuritis associated with chronic chylothorax in five cats and two dogs.

Severe bilateral fibrosing pleuritis was diagnosed in 5 cats and 2 dogs with chronic chylothorax. All animals were dyspneic on initial examination and remained moderately to severely dyspneic after thoracentesis. Radiographic evidence of fibrosing pleuritis included rounded lung lobes and failure of the lungs to reexpand following effective pleural drainage. Fibrosing pleuritis was also suggested in several animals with radiographic evidence of pleural fluid, in which pleural fluid could not be retrieved. Macroscopically, the lung lobes of all animals were compressed and atelectatic to various degrees, and the pleura appeared to be diffusely thickened and roughened. In several animals, fibrous adhesions were found between the parietal and visceral pleura of some lobes. Lung lobes were markedly constricted and appeared as small, smooth, rounded hilar masses in 4 animals. Mild to moderate pulmonary edema was evident in 3 animals at necropsy. Six of the 7 animals died (2) or were euthanatized (4) within 72 hours after the diagnosis of fibrosing pleuritis. The fibrosing pleuritis developed in 1 animal with lymphoblastic lymphosarcoma and chylothorax after treatment via passive pleuroperitoneal drainage; this animal was euthanatized because of underlying neoplasia. One cat, in which decortication was performed and resulted in marked reexpansion of the lung lobes, died 4 hours after surgery with signs compatible with pulmonary edema. On the basis of our findings, we suggest that animals with chronic chylothorax are at risk to develop fibrosing pleuritis. Furthermore, animals with severe bilateral fibrosing pleuritis should be given extremely guarded prognoses.

Animals↗

PubMed1992

Distribution of buccalin-like immunoreactivity in the central nervous system and peripheral tissues of Aplysia californica.

The neuropeptide buccalin A was originally purified and sequenced from a nerve-muscle system used in feeding-related behaviors of Aplysia californica in which it has been proposed that it acts as a modulatory cotransmitter. The distribution of buccalin-like immunoreactivity in the central ganglia and in peripheral tissues of Aplysia californica was examined by whole mount immunohistochemical techniques. Immunoreactive material was located in specific cell bodies and clusters of neurons in each of the ganglia. Immunoreactive fibers were present in each of the connectives between ganglia, in tracts coursing through the ganglia, and in the majority of the peripheral nerves. Most fibers were smooth in contour, but some had regularly spaced swellings. Varicosities containing immunoreactive material were located on specific neuronal somata and on certain tissues associated with the feeding, circulatory, digestive, and reproductive systems. The specific and widespread distribution of buccalin-like immunoreactivity supports the hypothesis that members of the buccalin peptide family act as neuromodulators or neurotransmitters in a variety of central and peripheral circuits in Aplysia.

Animals↗

PubMed1992

Peptidergic co-transmission in Aplysia: functional implications for rhythmic behaviors.

Despite their ubiquitous presence in the central and peripheral nervous systems, the behavioral functions of peptide co-transmitters remain to be elucidated. The marine mollusc Aplysia, whose simple nervous system facilitates the study of the neural basis of behavior, was used to investigate the role of peptidergic co-transmission in feeding behavior. Several novel modulatory neuropeptides were purified, and localized to identified cholinergic motorneurons. Physiological and biochemical studies demonstrated that these peptides are released when the motorneurons fire at frequencies that occur during normal behavior, and that the peptides modify the relationship between muscle contraction amplitude and relaxation rate so as to maintain optimal motor output when the intensity and frequency of feeding behavior change.

Amino Acid Sequence↗

PubMed1992

Pulsed spectral Doppler evaluation of a peripheral arteriovenous fistula in a horse.

Pulsed spectral Doppler ultrasonography was used to characterize the vascular involvement and anatomic boundaries of a peripheral arteriovenous fistula on the hemithorax of a horse. This information facilitated surgical removal of the fistula. Pulsed spectral Doppler evaluation of suspected peripheral vascular anomalies should be considered for the diagnosis of similar lesions, in which contrast angiography is not possible.

Animals↗

PubMed1992

Pneumothorax in a dog with a pulmonary abscess and suspected infective endocarditis.

Nontraumatic pneumothorax was diagnosed in a dog with a pulmonary abscess and evidence of infectious endocarditis, including fever, mitral murmur, and vegetative lesion of mitral valve leaflets. Pneumothorax persisted after 4 days of continuous thoracic drainage. At exploratory thoracotomy, the diaphragmatic lung lobe was identified as the source of air leakage and was excised. Results of culturing of blood and lung tissue for aerobic and anaerobic bacteria were negative. Antibiotics were administered because of suspected bacterial endocarditis. Pneumothorax and fever resolved after surgical and medical treatments.

Animals↗

PubMed1992

Chylous ascites in three dogs.

Chylous ascites was diagnosed in 3 dogs. Mesenteric lymphangiography was performed in 2 dogs and helped delineate abnormalities of the lymphatic system. The cause of chylous ascites in each dog appeared to be different. In 1 dog, a ruptured mesenteric lymphatic was identified at surgery. Evidence of abdominal lymphatic obstruction was found in another dog. Chylous ascites in the third dog appeared to be a complication of mesenteric lymphangiography for chylothorax.

Animals↗

PubMed1992

Failure to confirm increase in unscheduled DNA synthesis in sonicated mammalian cells in vitro.

Two in vitro mammalian cell lines (HeLa, mouse L5178Y) were exposed/sham exposed to ultrasound (2.3 or 2.6 MHz, I-SPTA 35 W cm-2, 10 microseconds burst duration, 200 Hz pulse repetition frequency) for 20 min and subsequently autoradiographically scored for unscheduled DNA synthesis (UDS). A positive control (20 and 40 J m-2 germicidal ultraviolet at a flux density of 1 J m-2 s-1) yielded statistically significant increases in UDS; no such increase was observed for the ultrasound regimens. The results fail to confirm an earlier report by Liebeskind et al. of ultrasound-induced increases in UDS.

Autoradiography↗

PubMed1992

Bubble cycling and standing waves in ultrasonic cell lysis.

Two quite different but potentially complementary hypothetical mechanisms have been proposed to explain the dependence of ultrasonic cell lysis in vitro on exposure vessel rotation. One mechanism proposes that resonant-size bubbles are trapped in planar arrays by standing waves in the sample and that exposure vessel rotation sweeps cells through the bubble arrays. The other mechanism, for which there is now considerable support, proposes that exposure vessel rotation simply allows bubbles to recycle after having been driven through the medium by the ultrasound. We report here the results of efforts to further discriminate between, and quantify, the relative contributions of these two mechanisms. Murine P388 cells were exposed to 1.07 MHz continuous-wave (CW) ultrasound for 5 min at 5 W/cm2 (ISP) using various exposure vessel compositions and exposure configurations. Experimental treatments were designed either to minimize or maximize standing waves in the sample tube, or to minimize the potential for bubble recycling while maximizing standing wave formation. The results of these experiments indicate that bubble cycling is responsible for the majority of cell lysis occurring in the rotating exposure vessels, but that a significant contribution to total lysis is provided by trapped bubbles under some conditions.

Animals↗

PubMed1992

Modest enhancement of ultrasound-induced mutations in V79 cells in vitro.

V79 cells were insonated (1 MHz, 35 W/cm2, 2 min continuous wave) under temperature conditions previously reported to cause a large increase in acoustic cavitation. The goal was to increase the ease of detecting ultrasound-induced mutations. The data supported the hypothesis that a 3 degrees C gas-equilibration period followed by insonation at 37 degrees C resulted in a detectable increase in resistance to 6-thioguanine with 6 trials per regimen.

Animals↗

PubMed1992

Apparent contribution of respiratory gas exchange to the in vitro "cell density effect" in ultrasonic cell lysis.

Ultrasonic damage to cells in vitro has been reported to vary dramatically with cell density; the particle density per se has been proposed to be responsible for this effect via interference with gas body activity. Reported here are the results of experiments designed to test the general postulate that the "cell density effect" can be explained in part by cellular modification of the suspension medium by respiratory gas exchange. Ultrasonic cell lysis is shown to occur at a much higher level in suspensions supplemented with the respiratory inhibitor NaCN than in control suspensions when suspension densities exceed 2 x 10(7) cells/mL. Moreover, at constant cell density, cell lysis diminishes with increasing pre-insonation incubation time at 37 degrees C. The rate of change in cell lysis with incubation time was diminished significantly by cyanide treatment. These observations are consistent with the postulate that respiratory O2:CO2 exchange enriches the medium in CO2 while depleting the medium of oxygen, which cavitates more readily than CO2, thereby diminishing the potential for cavitation-related cellular damage. However, this is only a partial explanation of the cell concentration dependence of cell lysis; cell density per se is an important factor in the "cell density effect."

Animals↗

PubMed1992

Regulation of macromolecular traffic mediated by the nuclear pore complex.

A sophisticated selective mechanism that regulates nuclear-cytoplasmic traffic has evolved in eukaryotes which circumvents the formidable barrier presented by the nuclear envelope. The sites of RNA and protein exchanges are the nuclear pore complexes (NPCs), 125 MDa supramolecular assemblies inserted into the envelope (see recent reviews by Dingwall, 1991; Goldfarb and Michaud, 1991; Miller et al., 1991; Nigg et al., 1991). In this article, the role NPCs play in regulating intracellular macromolecular traffic will be discussed.

Animals↗