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Biomedical subjects

P Miller

Publications and source records attributed to P Miller.

At least 217 records · Page 12Linked to original sources
PubMed1988

Effects of adherence, activation and distinct serum proteins on the in vitro human monocyte maturation process.

Elutriator-purified human monocytes were cultured in a serum-free (SF) medium, and various serum proteins and functional activating agents were assessed for their effects on the in vitro maturation of human monocytes to macrophages. Following 3 days of suspension culture in Teflon labware, 60% of the monocytes were easily recovered. When varying concentrations of human AB serum (HuAB) were employed, human monocyte maturation progressed rapidly; the kinetics of this maturation process during cell suspension culture were very similar to the pattern observed following adherence culture. In contrast, when SF medium was employed, a marked retardation of the monocyte maturation process was observed; this could not be attributed to any changes in cell recovery and/or viability. Thus, cells could be maintained in their monocytoid form for 3 days when cultured in SF medium. When HuAB was added after 3 days of culture, human monocyte maturation into macrophages proceeded at a normal rate. We attempted to characterize certain of the serum protein(s) found in HuAB which promoted the monocyte maturation process. Human immunoglobulin G (IgG) was found to be the most potent serum protein in increasing 5'-N activity and decreasing peroxidase activity of suspension cultured monocytes. Immunoglobulin M (IgM) and albumin (Alb) were shown not to have significant monocyte maturation activity. Heat-treated human gamma globulin and IgG purified by high-performance liquid chromatography (HPLC) were shown to have patterns identical with that of untreated HGG and IgG with regard to promoting monocyte maturation; F(ab')2 was not an active maturation promoter, indicating the need for an intact Fc portion of the IgG molecule. Fibrinogen and fibronectin also had maturation promoting activity. Finally, addition of the potent monocyte functional activators, muramyl dipeptide (MDP), polyriboinosinic:polyribocytidilic acid (Poly I:C), and lipopolysaccharide (LPS) had no effect on the monocyte maturation process. Thus, neither cell adherence or activation appear to be critical for the monocyte to macrophage maturation process. Instead, we hypothesize that in addition to proper nutritional support, a group of serum proteins (unified mainly by their ability to interact with monocyte membrane receptors) appear to be the principal promoters of this process.

5'-Nucleotidase↗
PubMed1988

Inverted vision after frontal lobe disease.

A case of bifrontal abscesses is reported. The patient claimed that he sometimes saw the world as if it were upside-down. A review of the literature reveals that, since 1805, 21 similar cases have been documented. The present case is unusual in that the neuropsychological status of the patient is investigated in some detail, and in that it seems to be the first report of inverted vision in a case of frontal lobe disease.

Brain Abscess↗
PubMed1988

Synthesis and oral antiallergic activity of carboxylic acids derived from imidazo[2,1-c][1,4]benzoxazines, imidazo[1,2-a]quinolines, imidazo[1,2-a]quinoxalines, imidazo[1,2-a]quinoxalinones, pyrrolo[1,2-a]quinoxalinones, pyrrolo[2,3-a]quinoxalinones, and imidazo[2,1-b]benzothiazoles.

4H-Imidazo[2,1-c][1,4]benzoxazine-2-carboxylic acid (3) was found to possess potent activity in the IgE-induced rat passive cutaneous anaphylaxis model which may be predictive of clinical antiallergic activity. Compared to disodium cromoglycate (DSCG, 1), 3 was less active following iv administration but unlike DSCG showed very significant oral activity. To explore the structural requirements for this activity, a range of tricyclic compounds was prepared and their activities were measured. Individual 2-carboxylic acids derived from imidazo[1,2-a]quinolines, imidazo[1,2-a]quinoxalines, imidazo[1,2-a]quinoxalinones, pyrrolo[1,2-a]quinoxalinones, pyrrolo[2,3-a]quinoxalinones, and imidazo[2,1-b]benzothiazoles showed iv activities up to 10(3) times as potent as DSCG and many of them showed significant oral activity. From these, imidazo[1,2-a]quinoxaline-2-carboxylic acid 114 has been chosen for further development.

Animals↗
PubMed1988

Bronchospasmolytic effects of RU 42173.

The bronchodilator properties of RU 42173, a new beta-adrenergic stimulant with an original structure, as a cyclic analogue of an arylethanolamine, have been evaluated on different in vitro and in vivo models and compared with those of salbutamol and isoprenaline. RU 42173 equipotently inhibited histamine-, acetylcholine-, and KCl-induced contractions in isolated guinea pig trachea or small bronchus and in isolated human bronchus. When administered to guinea pigs by the IV or aerosol route, RU 42173 dose-dependently inhibited bronchospasm induced by histamine, acetylcholine, and methacholine. It also inhibited PAF-induced bronchoconstriction and PAF-induced hyperreactivity to histamine. Moreover, RU 42173 had a rapid onset and prolonged duration of action. The potency of RU 42173 was similar to that of salbutamol.

Acetylcholine↗
PubMed1988

Molecular cloning and preliminary genetic analysis of the men gene cluster of Bacillus subtilis.

The Bacillus subtilis chromosomal locus that contains the genes encoding the menaquinone biosynthetic enzymes (the men genes) was cloned by using an integrable plasmid vector. The men cluster was reconstituted on three overlapping recombinant plasmids, and a tentative gene order was derived. Evaluations of the direction of transcription and of transcriptional boundaries suggested that the men genes are expressed in the form of at least one polycistronic message. In addition, a spectrum of Men phenotypes resulting from the integration of different internal fragments of the cluster indicate transcriptional complexities, possibly including an internal promoter. The size of cloned DNA fragments required to encompass the transcription unit, as well as the locations of known men mutations within these fragments, suggests that a gene(s) not previously identified with the men system is also located within the cluster. The cloned men sequences make available probes to examine the patterns of transcription from the men locus in response to changing environmental conditions and during the developmental sequence represented by endospore formation.

Bacillus subtilis↗
PubMed1988

Transcriptional regulation of a promoter in the men gene cluster of Bacillus subtilis.

The control of men gene expression during growth and sporulation of Bacillus subtilis was examined at the transcriptional level. Two different approaches were used. (i) Steady-state levels of men-specific mRNA were measured directly. (ii) A men'-lacZ gene fusion was constructed. In both cases, it was observed that men promoter activity was maximal at the onset of sporulation and declined soon thereafter. These kinetics were similar to the pattern of menaquinone accumulation previously observed. Expression from the men promoter was independent of the presence of the products of the spo0A and spo0H genes and was enhanced by addition of glucose and glutamine to the culture medium. DNA sequence analysis of the promoter region revealed a potential recognition site for the principal vegetative form of RNA polymerase but not for any of the known minor polymerase forms. The functionality in vivo of the promoter sequence was confirmed by high-resolution S1 nuclease mapping of the transcript start site. An additional sequence element was identified that is shared by the sdhA, citG, and ctaA promoters and may indicate a common regulatory mechanism in the expression of these genes.

Bacillus subtilis↗
PubMed1988

Studies on immunological air pouch inflammation in the rat.

The development of a novel immune-based model of inflammation in the subcutaneous air pouch of the rat is described. Rats were sensitized by injection with methylated bovine serum albumin emulsified with Freund's complete adjuvant and challenged 14 days later by injection of heat-aggregated antigen in saline into a 6-day subcutaneous air pouch. Time course studies revealed a peak polymorph cell infiltration at 24 h with no exudate formation, followed by a separate mononuclear cell response, rapid exudate formation, and granuloma formation over the 2- to 7-day period. Separate peaks of increased vascular permeability were observed in the acute and chronic phases of the response. This reaction was considered to be an example of delayed-type hypersensitivity based on its extended time course, the characteristic time course of oedema formation in foot-pad-challenged rats, and the failure of serum from sensitized rats to elicit a reversed passive Arthus-type reaction. The sensitization schedule was also shown to enhance the acute inflammatory response to carrageenan. In addition, the 'flare-up' reaction to secondary antigenic challenge was investigated in 7-day postchallenge lesions.

Adjuvants, Immunologic↗
PubMed1988

Early and late-phase bronchoconstriction after allergen challenge of nonanesthetized guinea pigs. I. The association of disordered airway physiology to leukocyte infiltration.

We describe a guinea pig model of asthma in which animals were sensitized and challenged by inhalation of aerosolized ovalbumin. Challenge was performed under cover of mepyramine (10 mg/kg) to allow a high enough concentration of ovalbumin to elicit consistent late responses. Airway resistance and thoracic gas volume of conscious guinea pigs was assessed by whole body plethysmography before and at regular intervals for as long as 72 h after challenge. At the same time points, cellular changes in the lung were assessed by both examination of cells recovered by bronchoalveolar lavage (BAL) and lung histology. There were no significant changes in specific airway conductance (SGaw), BAL cell content or lung histology in animals challenged with saline control. Challenge with 2% ovalbumin caused an early fall in SGaw, which peaked at 2 h and amounted to a 43.7 +/- 4.1% fall from baseline. This was followed by 2 late responses, the first reaching maximum at 17 h with a 46.9 +/- 4.5% decrease in SGaw from baseline and the second at 72 h with a 39.0 +/- 3.5% fall in SGaw. Examination of BAL fluid revealed a 7-fold increase in neutrophils at 6 h and a 17-fold increase at 17 h, after which numbers decreased to baseline. Eosinophilia developed more slowly, being insignificant at 6 h and 6-fold at 17 h; by 72 h, eosinophils constituted 48.9 +/- 6.9% of the total cells recovered. No changes in mononuclear cells or lymphocytes were observed. Histologic examination of the lung revealed a progressive eosinophil infiltration of the airways, but not alveoli or vascular bed. Electron microscopy showed degranulation of eosinophils recovered by BAL and discharge of mucus from goblet cells in the trachea. Because these changes are similar to those that occur after allergen challenge in human asthma, we suggest that this represents a useful animal model in which to study the mechanism of early and late bronchoconstriction responses.

Airway Resistance↗
PubMed1987

Fate of gamma-interferon-activated killer blood monocytes adoptively transferred into the abdominal cavity of patients with peritoneal carcinomatosis.

Five patients with colorectal cancer widely metastatic to peritoneal surfaces have been treated i.p. with infusions of autologous blood monocytes made cytotoxic by in vitro incubation with human gamma-interferon. The monocytes were purified by a combination of cytapheresis and counter-current centrifugal elutriation procedures; each week approximately 350 million activated monocytes were given to patients as adoptive immunotherapy by a single i.p. instillation. On the eighth cycle of treatment the trafficking of i.p. infused blood monocytes was studied in two patients by prelabeling the cells with 111In. These activated cells became distributed widely within the peritoneal cavity. Two and 5 days after infusion their position within the peritoneum had not changed. When peritoneal specimens were obtained 36 h after 111In-labeled monocyte infusion, labeled monocytes were demonstrated to be associated with the serosal surfaces by autoradiographic analysis. Scintiscanning structures outside the abdominal cavity revealed that 111In-labeled monocytes infused i.p. did not traffic to other organs during the 5 days of the study. We conclude that i.p. adoptive transfer of autologous killer blood monocytes is an effective way of delivering these cytotoxic cells to sites of tumor burden on peritoneal surfaces in these cancer patients.

Colonic Neoplasms↗
PubMed1987

Reaction of T lymphocytes with anti-T3 induces translocation of C-kinase activity to the membrane and specific substrate phosphorylation.

Reaction of the T cell membrane with monoclonal antibodies to T3 can initiate cellular activation, and this is associated with increased intracellular Ca2+ and inositol-trisphosphate (IP3) release. We therefore studied the possible involvement of Ca2+/phospholipid-dependent kinase (C-kinase) in these phenomena. Quantitative assays of exogenous substrate phosphorylation in unstimulated cells showed Ca2+/phospholipid-dependent kinase activity in the cytosol, but no comparable activity in the particulate fractions corresponding to membrane and cytoskeleton material. At concentrations of soluble anti-T3 that partially activate T cells in the absence of macrophages, there was a 50 to 60% decrease in C-kinase activity in the cytosol, with a comparable increase in activity in the membrane fraction. A similar transfer of activity was also induced with the known C-kinase activator, 12-O-tetradecanoyl-phorbol-13-acetate, although redistribution was more rapid in onset, more complete, and more sustained. Redistribution of enzyme activity was additionally confirmed by qualitative assays of endogenous substrate phosphorylation. Labeling of intact cells followed by immunoprecipitation analysis with anti-T3 indicated signal-dependent phosphorylation of two components of the T3 complex and an unidentified 94,000 substrate that was resistant to reduction and alkylation. These findings are consistent with an important role for C-kinase in transduction of membrane events by the T3-Ti complex.

Antibodies↗
PubMed1987

Pseudomonas putida. Newly recognized pathogen in patients with cancer.

Pseudomonas putida was recovered from blood culture specimens between 1980 and 1985 in 15 patients with cancer. No isolates were found in specimens obtained before 1980. Eight patients were considered to have septicemia (more than one positive blood culture result plus clinical signs of infection). Septicemia was monomicrobial in three of those eight patients and polymicrobial in five. Of these eight patients, one had pneumonia and three had phlebitis, cellulitis, or both at the site of the venous catheter. The infection appeared to be catheter-related in these three patients, with response to catheter removal in one patient, response to catheter removal and antibiotics in one patient, and response to antibiotics alone in one patient. P. putida was isolated from the site of insertion and the tip of the catheter in one of these three patients. Following therapy, all patients had a rapid recovery from their infection. In vitro susceptibility testing revealed that 90 percent of the isolates were susceptible to piperacillin, ceftazidime, imipenem, and ciprofloxacin.

Catheterization↗
PubMed1987

Microsequence analysis of peptides and proteins. VI. A continuous flow reactor for sample concentration and sequence analysis.

We have designed and tested a continuous flow reactor (CFR) for microsequence analysis of peptides and proteins. The CFR forms the site for immobilization of the peptide or protein substrate and automated Edman chemistry. The CFR was constructed from 0.125-in.-o.d., 0.0625-in.-i.d. Teflon tubing (length 2-3 cm) containing 5-10 mg of Polybrene-coated, spherical, porous silica (100-200-micron particle size). The silica is retained in the CFR with porous Teflon filters (Zitex) at the bed bottom and optionally at the bed top. The i.d. of the CFR was selected for a tight press fit when 0.0625-in.-o.d. Teflon lines are inserted at the top and bottom of the CFR. This design allows the replacement of the existing cartridge/glass fiber disk found in conventional microsequencers with a CFR with a minimal amount of changes. The advantages of the CFR over the previous design include a lower background or noise level and no need to precycle Polybrene before sample application, and the entire unit is inexpensive and therefore disposable. We believe that the decrease in noise, especially the decrease in the commonly observed diphenylthiourea peak, is due to the more direct flow path and relative absence of unswept area in the CFR. Several standard peptides and proteins were sequenced in the CFR to demonstrate the improved results. A direct comparison to the cartridge/glass fiber disk design demonstrated less background and higher initial and repetitive yields for the CFR. An additional advantage is the ability to directly concentrate samples on CFRs containing reverse-phase packing. We have successfully concentrated 1.0-ml samples (200 pmol) onto 5 mg of octyldecylsilyl-derivatized silica in yields of 95-100%. The resulting samples were microsequenced after addition of Polybrene-coated silica to the CFR with high initial and repetitive yields. This methodology promises to improve sample handling and microsequence analysis of low picomole amounts of peptides and proteins.

Amino Acid Sequence↗
PubMed1987

Pharmacological modulation of erythrocyte autoimmune reactions in mice.

Injection of mice with rat erythrocytes induces both anti-rat and autoimmune anti-erythrocyte responses. The autoimmune response is under active suppression which can be demonstrated by transfer of spleen cells from immunised donors to naive recipients subsequently injected with erythrocytes. This system allows investigation of immunemodulatory agents on responses to self and non-self antigens in three ways the autoantibody and anti-rat erythrocyte responses in mice receiving the drugs and rat erythrocytes; the responses in mice receiving transferred cells from dosed immunised donors; and the responses in mice receiving transferred cells from non dosed immunised donors and themselves receiving erythrocytes plus drugs. The effect of a range of compounds with immunemodulatory activity was examined in the three test situations and both suppression and enhancement of the autoimmune response were observed. Comparison of effects on anti-rat and autoimmune antibody levels has confirmed previous results that these responses are subject to separate controlling mechanisms.

Animals↗
PubMed1987

Transclival penetrating injury.

A case of a stab wound of the cranium with a retained knife blade is presented. The blade had an unusual course through the base of the skull--the point of the knife penetrated the clival line to end in the posterior fossa. Although the blade was in close proximity to the basilar artery, it was judged safe to extract the knife by blind removal. The patient had no neurological deficit postoperatively.

Adult↗
PubMed1987

Videofluoroscopic and scintigraphic analysis of dysphagia in the head and neck cancer patient.

This paper presents two advances in the evaluation of swallowing function which better define the swallowing processes in the head and neck cancer patient. Videofluoroscopy, improved by computer-assisted image analysis, provides more accurate information regarding oral and pharyngeal movement of structures. Radionuclide scintigraphy, a complementary technique, quantitates bolus flow (transit times) and the degree of aspiration. Several cases demonstrate the advantages of the methods and their usefulness in evaluating the effects of cancer treatment. The improved techniques also provide opportunity for designing new strategies of medical and surgical rehabilitation.

Adult↗