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Biomedical subjects

D M Miller

Publications and source records attributed to D M Miller.

At least 181 records · Page 10Linked to original sources

Breathing systems for use in anaesthesia. Evaluation using a physical lung model and classification.

A lung model which measures effective alveolar ventilation is described and used to evaluate different breathing systems during simulated spontaneous ventilation. The model measures VD/VT ratios in relation to fresh gas flow and the characteristic shape of the resulting curve characterizes the particular breathing system. The various curves reflect the functional performance and, therefore, the flow requirements of the systems which have been reclassified accordingly. The classification described is based upon the structural arrangements which determine the flow patterns within the particular systems. The breathing systems compared during spontaneous ventilation were a circle "C" absorber system, the circle "C" without the absorber, the Mapleson A, B, C and D systems and a series of "enclosed" and modified Mapleson A systems and the modified Mapleson D or Bain system.

Anesthesia, Closed-Circuit↗

Inhibition of 2-aminofluorene mutagenesis in bacteria by inducers of cytochrome P-450d.

Certain chemical inducers of rat liver microsomal cytochrome P-450d are tightly bound to the cytochrome. We investigated the ability of two inducers of cytochrome P-450d, Aroclor 1254 and isosafrole, to inhibit the microsomal activation of 2-aminofluorene to a mutagen as measured in Salmonella typhimurium. Butanol treatment of microsomes from isosafrole-treated rats removed an inhibitory metabolite of isosafrole and increased 2-aminofluorene mutagenesis by approximately 2-fold over controls. Butanol treatment of microsomes from Aroclor 1254-treated rats failed to either remove any of the Aroclor 1254 associated with microsomal cytochrome P-450 or affect 2-aminofluorene-induced mutagenesis. However, addition of Aroclor 1254 to butanol-treated microsomes from isosafrole-treated rats almost completely inhibited 2-aminofluorene mutagenesis. Aroclor 1254 completely inhibited the cytochrome P-450d-dependent estradiol 2-hydroxylase activity of butanol-treated microsomes from isosafrole-treated rats. Thus, we suspect that certain congeners from Aroclor 1254, a widely used mixture for induction of cytochrome P-450 activities, could inhibit cytochrome P-450d and partially mask its ability to metabolize some chemicals to mutagens.

Animals↗

Clinical use of a standard kit-preparation of radiolabeled monoclonal antibody 96.5 in the diagnostic imaging of metastatic melanoma.

We studied the efficiency of a standard-kit preparation using 1 mg 111In-labeled 96.5 monoclonal antibody in combination with 19 mg of unlabeled antibody in the diagnostic imaging of 27 patients with documented metastatic melanoma. Twenty-three of 26 patients (88%) demonstrated immunoscintigraphic localization of tumor. Of 104 metastatic sites previously documented by conventional studies, 62 (60%) were identified by immunoscintigraphy. A total of 77 sites demonstrated localization of radiolabeled antibody. Fifty-four (70%) corresponded to known sites of disease; eight sites (10%) were "discovered" by immunoscintigraphy and subsequently confirmed by conventional studies; 15 imaged sites (20%) could not be confirmed by conventional studies. Size and location of metastasis appear to be important features that influence imaging efficiency. Tumor size (greater than or equal to 2 cm v less than 2 cm) appears to be the statistical dominant determinant. The feasibility and potential clinical use of radioimmune imaging of tumors is discussed.

Adult↗

Cell culture studies and oncogene expression in juvenile chronic myelogenous leukemia.

Juvenile chronic myelogenous leukemia (JCML) may be distinguished from adult CML based upon in vitro cell growth characteristics. We studied four untreated children with JCML and report additional unique findings. Peripheral blood (PB) and bone marrow (BM) cells were grown in soft agar. Without exogenous colony-stimulating activity (CSA) there was exuberant "spontaneous" colony formation in both PB and BM cultures. In the absence of exogenous stimulus, PB colony morphology was predominantly, but not exclusively, monocyte/macrophage. When PB was depleted of adherent cells, "spontaneous" colony formation was nearly completely abrogated. Cultures were also performed in the presence of various sources of CSA including giant cell tumor-conditioned medium (GCT-CM), a melanoma cell line-CM (LD1-CM), human placenta-CM (HPCM), and normal PB mononuclear cell (PBMC) feeder layers. Colony formation was typically increased with HPCM and PBMC, whereas in two patients GCT-CM and LD1-CM failed to stimulate additional colony growth when compared to cultures without exogenous CSA and, in fact, appeared to inhibit baseline "spontaneous" growth. The morphology of colonies in the presence of exogenous stimuli was highly variable. Because of the recent association between the c-fms protooncogene product and the receptor for the monocyte growth factor CSF-1, we analyzed the PB cells from two JCML patients for c-fms expression. Although expressed, c-fms levels were less than that in an adult with Ph1-positive CML in chronic phase. These studies indicate that in JCML, there are dramatic increases in both PB and BM colony-forming cells and that "spontaneous" growth is dependent on an accessory adherent cell fraction. Furthermore, patterns of responsiveness to various sources of CSA suggest that the colony-forming cells may not be a uniform population of malignant cells.

Animals↗

The results of cryosurgical treatment of cervical intraepithelial neoplasia at one, five, and ten years.

The results after cryosurgical treatment of cervical intraepithelial neoplasia at 1, 5, and 10 years are reported. Ninety-four percent of the 1675 patients eligible for assessment at 1 year were successfully treated, with only 5.6% lost to follow-up. After 5 years, 14% of patients were lost to follow-up, but the corrected success rate remained essentially unchanged. No major differences in success rates were noted for the various histologic grades of cervical intraepithelial neoplasia treated. A small but definite percentage of patients developed further disease over the ensuing years, indicating the need for long-term, continued surveillance of these patients.

Adult↗

Modulation of immune responses in mice by d-limonene.

The immunotoxicologic effects of d-limonene were determined. This naturally occurring substance is widely used in food flavorings and is a common additive in cosmetics. In the present study, BALB/c mice were treated with d-limonene for 9 wk. Effects on T- and B-cell responses were determined after 4 and 8 wk of treatment. Concanavalin-A responses at 8 wk, but not 4 wk, were suppressed in treated mice. A similar trend was observed for phytohemagglutinin and lipopolysaccharide responses. Evidence was presented that d-limonene had polyclonal activator action. Mice primed with keyhole limpet hemocyanin (KLH) prior to initiation of d-limonene treatment had suppressed primary and secondary anti-KLH responses. Mice treated with d-limonene prior to KLH priming produced significant increased antibody responses. Additional evidence for polyclonal stimulation was obtained by histopathologic examination of secondary lymphoreticular tissue. Significant secondary follicle development and prominent lymphoid nodules and aggregates were found in the pancreas and intestinal mucosa, particularly apparent in mice receiving the highest d-limonene dosage. A subchronic LD50 study was conducted wherein BALB/c mice received 16 daily doses of d-limonene. An LD50 of approximately 0.0850 mg d-limonene/kg (corrected for 82% purity) was determined.

Animals↗

Mithramycin selectively inhibits transcription of G-C containing DNA.

Mithramycin induces a reversible inhibition of cellular RNA synthesis without affecting DNA synthesis. The authors have shown this drug induces myeloid differentiation of HL-60 promyelocytic leukemia cells and is an effective agent in certain patients with chronic granulocytic leukemia. In order to investigate the mechanism by which this drug inhibits RNA synthesis we have compared the effect of mithramycin on RNA synthesis by whole cells, isolated nuclei, and RNA synthesis by isolated E. coli RNA polymerase and eukaryotic RNA polymerase II. Exposure of HL-60 cells to mithramycin at concentrations of 4.6 X 10(-7) m or higher for 48 hours causes an almost immediate inhibition of RNA synthesis (up to 85% at 4 hours) with only modest cytotoxicity at these concentrations. Endogenous RNA synthesis by isolated nuclei can be inhibited by mithramycin only at high concentrations (greater than 10(-5) m), suggesting that mithramycin primarily may inhibit initiation, rather than elongation. Mithramycin inhibits in vitro transcription of salmon sperm DNA by E. coli RNA polymerase at DNA:drug ratios similar to those required for RNA synthesis inhibition in whole cells. Similar DNA binding studies with synthetic oligonucleotides demonstrate that mithramycin is a potent inhibitor of transcription of Poly dG.dC by E. coli RNA polymerase but has no effect on transcription of Poly dA.dT. The rapid inhibition of whole cell and isolated RNA polymerase transcription, and the relative insensitivity of isolated nuclei, suggest mithramycin may interact with specific DNA sequences in order to inhibit the initiation of RNA synthesis in intact cells.

Base Composition↗

Errors in the Measurement of Root Pressure and Exudation Volume Flow Rate Caused by Damage during the Transfer of Unsupported Roots between Solutions.

Plants of Zea mays were grown with their roots confined to growing tubes, consisting of cylindrical or spherical glass tubes fitted at the bottom with a stopcock. Nutrient solution was circulated past the roots, and when a plant was 21 to 25 days old, the stopcock was closed, the root excised from the plant and connected to an apparatus which measured root pressure and exudation volume flow rate. The stopcock was opened and solution was again circulated through the growing tube without dropping the level of the liquid bathing the root in the process. Measurements of pressure and flow rate were made continuously during a period in which the solution was replaced, first by draining and refilling the tube in situ, and second by replacing the growing tube with a beaker of solution. Both these manipulations caused at least temporary and frequently permanent drops in root pressure and flow rate. Plants were also grown in cylindrical tubes with a support medium of either glass beads or Raschig rings which filled the growing tubes. It is shown that the solution bathing these roots could be repeatedly replaced by draining and refilling with no visible effect on the measurements. It is recommended, therefore, that in future, support be provided for the roots of all experimental plants grown by solution culture.

Journal Article↗

Computerized axial tomography (CT) as an aid in the diagnosis of hepatic portal venous gas: a case report.

The radiologic finding of hepatic portal venous gas and its surgical implications have been documented previously in the literature. More than 67 cases have been reported. Branching tubular lucencies that extend from the porta hepatis to the edge of the liver are characteristic. In general, air in the biliary tree is central in location, but the distinction may not always be clear. We present a case in which computerized axial tomography was extremely helpful in localizing extraluminal gas to the liver and differentiating between air in the biliary tree and hepatic portal venous gas.

Gases↗

Preliminary observations on the therapy of the myeloid blast phase of chronic granulocytic leukemia with plicamycin and hydroxyurea.

We observed a dramatic improvement in the peripheral blood counts of a patient in the myeloid blast phase of chronic granulocytic leukemia after plicamycin (mithramycin) therapy of concurrent hypercalcemia. We then treated eight additional patients in the blast phase of chronic granulocytic leukemia with a combination of alternate-day plicamycin and daily hydroxyurea. All six patients with myeloid morphology at the time of blast crisis responded with a return to a chronic phase without an intervening pancytopenic period. Of three patients with lymphoid morphology at the time of treatment, only one responded (this patient had recently relapsed and converted from myeloid to lymphoid morphology). Another patient with nonmyeloid, nonlymphoid blast morphology also did not respond. Continual therapy with the two-drug combination appeared to be necessary, since early relapses were seen in responding patients whose therapy was interrupted. These data are preliminary and will need further confirmation, but they suggest that the combination of alternate-day plicamycin and daily hydroxyurea may be effective in the myeloid blast phase of chronic granulocytic leukemia.

Adult↗

Immunological identification of the genes encoding the four myosin heavy chain isoforms of Caenorhabditis elegans.

The nematode Caenorhabditis elegans produces four distinct myosin heavy chain (MHC) isoforms, A, B, C, and D. The MHC A and MHC B proteins are coordinately expressed in the body wall muscle and are incorporated into different regions of a single kind of thick filament. MHC C and MHC D are exclusively produced in the pharyngeal muscle. Previous studies of mutations that affect MHC B have shown that this isoform is encoded by the unc-54 gene. Three other MHC genes, myo-1, myo-2, and myo-3, were isolated from a C. elegans genomic library by hybridization with fragments of the unc-54 gene. We have now established the MHC isoform encoded by each gene. Restriction fragments from each of these genes were cloned in the plasmid expression vector pUR288, producing fusion proteins between Escherichia coli beta-galactosidase and portions of the MHC rod domains of each gene. The hybrid proteins were screened with a panel of 18 isoform-specific monoclonal antibodies. The results demonstrate that myo-1 encodes MHC D, myo-2 encodes MHC C, and myo-3 encodes MHC A.

Animals↗

Basic mechanisms of metastasis.

Metastatic disease is responsible for the majority of deaths caused by cancer. The process of metastasis is an orderly, stepwise process that results in the selection of cells that possess the capability to establish viable metastases. These cells must be locally invasive and be able to survive the physical traumas of dissemination and normal host defenses. Once metastatic cells have been arrested in a capillary bed, they must be able to invade the host organ parenchyma and survive in that milieu. Studies in a number of model systems have documented the phenotypic alterations in cells that have "metastatic potential." These differences may stem from normal tumor cell heterogeneity and surprisingly reflect only minor differences in gene expression. The role of activated oncogenes in metastasis is unclear, but a number of laboratories have documented that transfection with activated Ha-Ras results in increased metastatic potential. An increased understanding of the genetic basis of metastatic potential may suggest new directions for intervening in this deadly process.

Humans↗

A review of protonephridial excretory systems in Acanthocephala.

Our present understanding of the excretory system of Acanthocephala is largely the result of work done by 5 German scholars: Kaiser, Schepotieff, Meyer, Kilian, and von Haffner. Present studies indicate that a protonephridial system is restricted to the family Oligacanthorhynchidae. However, many members of this family have not had a protonephridial system described. Three nephridial designs have been described: 1) dendritic type, organized as branches of a tree where each final branch terminates in a ciliated bulb; 2) capsular type, in which all ciliated bulbs empty directly into a common chamber; and 3) rudimentary type, consisting of a single cell with a patent ciliary pouch but no ducts to the outside. The first 2 types are a syncytia with 3 nuclei located in the capsule or stem wall and none in the flame bulbs. These excretory systems consist of 2 clusters of flame bulbs that empty separately into an expandable excretory bladder which in turn empties into ducts of the reproductive system. This urogenital system empties to the outside through a gonopore located at the tip of the penis in males and the posterior terminus of the vagina in females. Cilia occur in certain excretory tubes, depending on sex and species, but are unknown in the excretory bladder or ducts leading into it. The rudimentary type consists of a cell whose posterior extension terminates near the bursal lumen, but it is not known if this is significant for the discharge of material. There is no information on the physiology or biochemistry of the excretory system or its products.

Acanthocephala↗

Gall bladder anomaly in a young chicken.

A multi-cystic gall bladder was observed at necropsy in a 7-week-old broiler cockerel. Cystic lumina contained multiple elongated papillary epithelial projections and plicae composed of epithelium and lamina propria, abutting normal lining epithelium.

Animals↗

Trichosporon infection in a cat.

A protruding nasal mass in a domestic shorthair cat with nasal discharge and recurrent fever was determined to be caused by infection with the fungus Trichosporon pullulans, as determined by cytologic, histologic, and fungal culture methods. Initially, the cat was treated orally with ketoconazole and the mass decreased in size. When signs of hepatotoxicosis developed, treatment was reduced to an alternate-day basis. However, the nasal mass increased in size with this regimen, and therapy with amphotericin B and 5-flucytosine was begun. It also was unsuccessful.

Amphotericin B↗