Search PubMed⌕ Search

Biomedical subjects

P Miller

Publications and source records attributed to P Miller.

At least 253 records · Page 14Linked to original sources
PubMed1985

A lung perfusion technique for the detection of antigenic intrapulmonary bronchoconstriction and its mediation.

A guinea pig intraluminal perfusion model was used to assess the effects of antigen challenge of airway reactivity and its pharmacologic modulation. Increases in airway perfusion pressure, following antigen provocation, could be reproduced 60 min later without significant modification of the response. We found no change in lung volume nor observed tissue edema following antigen provocation, and suggest that rises in perfusion pressure are due to decreases in airway caliber. Pharmacologically, the antihistamines, mepyramine and chlorpheniramine, and the antiallergic agent, disodium cromoglygate (DSCG), failed to inhibit antigenic bronchoconstriction. Indeed, mepyramine produced some potentiation of allergic bronchospasm. Compounds reported to inhibit 5-lipoxygenase (phenidone, benoxaprofen, and noradihydroguiaretic acid (NDGA)) or antagonize SRS-A (FPL 55712), produced inhibition of antigen-induced bronchoconstriction. The cyclooxygenase inhibitor, indomethacin, produced biphasic modulation of antigenic bronchoconstriction, potentiation at low doses, and inhibition at high concentrations. Overall, drug-induced modulation of allergic bronchoconstriction suggests that this model more closely resembles the antigenic reactions observed in the parenchymal strip preparation than in the trachea.

Animals↗
PubMed1985

Jejunal diverticulosis: medical and surgical management.

Jejunal diverticulosis, a marker of disordered small intestinal motility, presents varied clinical manifestations. It is important to consider this disorder in elderly patients with unexplained abdominal discomfort accompanied by signs of intermittent small bowel obstruction and malabsorption. Diagnosis can be made by a small bowel follow-through x-ray film obtained as part of the evaluation of diarrhea and obstructive symptoms. Medical therapy is helpful in controlling diarrhea and anemia, while surgical therapy can give excellent results in treating complications or refractory symptoms.

Aged↗
PubMed1984

Characterization of biological response modifier release by human monocytes cultured in suspension in serum-free medium.

Human monocytes have been shown to be critical immunoregulatory cells for a variety of frequently measured in vitro human immune functions and are secretors of potent biologic response modifiers ( BRMs ). These BRMs , such as interferon (IFN), colony stimulating factor (CSF) and prostaglandin E (PGE), may play important roles in the host immune response to cancer. A new approach for culturing circulating peripheral blood monocytes has been developed to retain the native characteristics of these cells, avoiding possible alteration or activation by adherence. The ability of elutriator-purified human monocytes to secrete IFN and PGE was examined under conditions of suspension culture as well as after adherence, and no difference in secretion of these BRMs was noted. In contrast, Teflon-cultured monocytes demonstrated a significantly enhanced CSF release over culturing in polystyrene plates. A new serum-free medium has also been developed, and monocytes cultured in vitro in this medium showed a 5-fold increase in IFN release, and up to a 72% increase in CSF release when compared to optimal standard culture medium (containing 10% AB serum) and an increased stimulation index for PGE release. By these procedures, hundreds of millions of highly purified human monocytes can be sterilely isolated in suspension and cultured in suspension in serum-free medium with retention of BRM-releasing capabilities. This system should permit more detailed molecular studies of monocytes (in which serum can be an impediment) and may also facilitate clinical therapy studies involving the in vivo transfer of monocytes activated in suspension in vitro.

Blood Physiological Phenomena↗
PubMed1984

Characterization of purified cryopreserved human monocyte function in assays of superoxide production, accessory cell function, chemotaxis, and in fluorescent cell sorter analysis.

The ability to use highly purified cryopreserved human monocytes in various in vitro assays has a number of practical and theoretical advantages, including convenience and the potential for enhanced reproducibility. Large numbers (up to 1 X 10(9)) human monocytes can be isolated from a single donor in a purified suspension state, by a combination of leukapheresis and counter-current centrifugal elutriation (CCE) technologies. Following short- and long-term periods of cryopreservation, the viability and phagocytic function of these CCE-purified monocytes was unimpaired. Cryopreserved monocytes were similar to fresh cells in their ability to release superoxide anion (O2-), although unstimulated and stimulated O2- release values tended to increase slightly following weeks to months of cryopreservation. In contrast, even short-term cryopreservation diminished both the random migration and chemotactic responses of human monocytes; however, cryopreserved monocytes could be employed in this assay provided the calculated chemotactic ratio (chemotactic migration/spontaneous migration) was used. Cryopreserved monocytes demonstrate 70% of fresh monocyte accessory cell function in pokeweed mitogen-induced lymphocyte proliferation assays. When the binding of OKT3, OKM1, anti-DR, and fluoresceinated pokeweed mitogen to monocytes was analyzed in the fluorescence activator cell sorter (FACS), cryopreserved and fresh monocytes displayed a similar pattern of membrane reactivity.

Chemotaxis, Leukocyte↗
PubMed1984

Uptake and metabolism of cisplatin by rat kidney.

Cisplatin, an effective antineoplastic agent, is toxic to the kidney. Since the kidney's vulnerability to cisplatin may originate in its ability to accumulate and retain platinum to a greater degree than other organs, we studied the characteristics of the renal accumulation of platinum and investigated the nature of intracellular platinum. Cisplatin and ethylenediamminedichloroplatinum, nephrotoxic and antineoplastic liganded platinum compounds, were concentrated in rat renal cortical slices fivefold above medium concentration. Platinum uptake was energy- and temperature-dependent and could be inhibited by drugs which inhibit base transport. The organic anions para-aminohippurate and pyrazinoate did not reduce renal slice platinum uptake. Unbound platinum in the blood and urine was predominantly cisplatin but unbound platinum in kidney cytosol was not. This latter compound, in contrast to cisplatin, was not active as a mutagen. These studies suggest that the kidney accumulates platinum in part by transport or specific binding to the base transport system in the kidney and biotransforms it intracellularly. Unbound platinum in the cell is not cisplatin and may no longer be toxic.

Animals↗
PubMed1984

Activation of the oxidative burst in human monocytes is associated with inhibition of methionine-dependent methylation of neutral lipids and phospholipids.

Chemotaxis and generation of the oxidative burst by phagocytes are among the biological functions thought to require methylation reaction(s) for their expression. The present study investigated the effect of different stimuli of the oxidative burst on lipid methylation by human elutriated monocytes as measured by methyl group incorporation from [methyl-3H]methionine into both phospholipid and neutral lipid extracts. Normal monocytes, incubated at 37 degrees C for 1 h with 2 microM methionine, incorporated 10.2-fmol/10(6) cells and 73.6-fmol/10(6) cells of methyl groups into neutral lipids and phospholipids, respectively. Stimulators of the respiratory burst, such as the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine, the tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate, and the calcium ionophore, A23187, decreased the incorporation of methyl groups into both neutral lipids and phospholipids in a similar manner. Increasing the concentration of methionine in the medium reversed or attenuated the inhibition achieved at lower levels. An inverse relationship existed between the degree of methylation and the extent of stimulation of the oxidative burst, measured as superoxide anion (O-2) release. Stimulated monocytes oxidized methionine to methionine sulfoxide (which cannot act as a methyl-donor), and this was dependent on activation of the respiratory burst. Elimination of the accumulated methionine sulfoxide by replacement of the medium or by prevention of extracellular methionine oxidation by catalase did not effectively restore the normal level of methylation in stimulated cells, and the reduced methylation was not primarily related to a defective methionine uptake by stimulated monocytes. These data suggest that intracellular events related to activation of the respiratory burst are responsible for the decreased lipid methylation in stimulated cells, possibly by their leading to intracellular formation of methionine sulfoxide and by their limiting the availability of methyl-donor. This mechanism may be of potential relevance for the expression of biological functions where methionine-dependent reactions are involved.

Calcimycin↗
PubMed1983

A system for obtaining large numbers of cryopreserved human monocytes purified by leukapheresis and counter-current centrifugation elutriation (CCE).

A system has been developed for the isolation of large numbers of unfractionated mononuclear cells from single, well characterized normal individuals and for the separation by elutriation of these cells into populations of greater than 90% pure monocytes and greater than 99% pure lymphocytes. The total number of monocytes obtained from a single donor averaged about 550 million. After cryopreservation and thawing of these cells, the viability remained greater than 90%, 80% of original cells were recovered, and the ability to ingest antibody-coated targets was comparable to that of fresh monocytes. The cells remained sterile without the use of antibiotics and were suitable for long-term culture. The monocytes that were isolated and cryopreserved by these procedures functioned reproducibly as inhibitors of tumor cell growth and in an assay of responsiveness to monocyte migration inhibitory factor (MIF).

Blood Preservation↗
PubMed1983

Combined modality therapy for esophageal squamous cell carcinoma.

Of 55 patients with esophageal squamous cell carcinoma, 30 with localized disease were treated with a combined modality for curative intent. Treatment consisted of mitomycin C (10 mg/m2 day 1) and continuous infusion 5-FU (1000 mg/m2 day, days 1-4, 29-32) (CT), radiation (XRT) (3000 rad, days 1-21) with nutritional support, and surgery (days 49-64). Surgery consisted of celiotomy, esophagectomy and esophagogastrostomy +/- postoperative ventilatory support. Postoperative CT plus an additional 2000 rad XRT was restricted to patients with histologic positive tumor. Since five resected patients with subclinical metastatic tumor had an inferior survival equal to 25 patients treated essentially for palliation, pretreatment celiotomy seems warranted to identify patients with an inferior prognosis. Of 18 resected patients without disseminated tumor evaluable for this combined modality: six were tumor free, three had intramural and nine transmural tumor; the median survival is 76 weeks and five of six living patients are disease free at 95-190 weeks; and local recurrence occurred in two and in two of seven unresected patients. Since toxicity was minimal except for postoperative pneumonitis (13%) and local recurrence low (13%), two courses of chemotherapy and 5000 rad XRT perhaps obviates the need for resection.

Abdomen↗
PubMed1983

Cortical and papillary absorptive defects in gentamicin nephrotoxicity.

Renal function was examined in rats given daily injections of gentamicin (100 to 150 mg/kg) for 10 to 14 days. Whole kidney inulin clearance fell and urine volume increased. Single nephron GFR of surface nephrons varied. Some nephrons had no filtration, some had low rates, and some had high rates. Abnormal renal tubular epithelial inulin permeability was demonstrated by microinjection. Micropuncture of individual nephrons early and later in their course demonstrated reduced fluid reabsorption along the proximal convoluted tubule of superficial nephrons. Rates of fluid delivery to the late proximal and distal tubule were elevated. The rate of fluid reabsorption in the superficial loop of Henle was increased. Maximal urine osmolality and papillary tissue content of urea was reduced. The polyuria, therefore, results from decreased fluid reabsorption by proximal tubules and, probably, by papillary collecting ducts. The decrease in proximal fluid reabsorption is probably secondary to impaired solute reabsorption. A decrease in collecting duct fluid absorption can be attributed to the observed decrease in papillary solute concentration.

Acute Kidney Injury↗
PubMed1983

Chlormethiazole in the treatment of neonatal status epilepticus.

A pre-term neonate with status epilepticus resistant to conventional treatment but who responded to a chlormethiazole infusion is reported. Nineteen days of continuous infusion was required before treatment could be discontinued and oral phenytoin substituted. Chlormethiazole should be considered in the treatment of resistant convulsions in the newborn.

Chlormethiazole↗
PubMed1983

Intracellular bile acid transport in rat liver as visualized by electron microscope autoradiography using a bile acid analogue.

The role of hepatocyte organelles in the intracellular transport and secretion of conjugated bile acids has not been defined. Therefore we studied the transport and observed the subcellular localization of the bile acid analogue 125I-cholylglycyltyrosine by electron microscope autoradiography to further understand the possible compartmentation of bile acids within the hepatocyte. 125I-cholylglycyltyrosine, which retains a net negative charge, exhibited transport properties similar to native bile acids. After portal vein injection, the compound was recovered intact from bile, and the pattern of excretion paralleled that of [14C]cholylglycine. In addition, cholylglycyltyrosine uptake by isolated hepatocytes was sodium dependent. For autoradiography the analogue was injected into the portal vein, and the liver was perfusion fixed after 30 or 300 s. Light microscope autoradiography performed 30 s after isotope injection demonstrated a steep periportal-to-centrilobular gradient for 125I-cholylglycyltyrosine uptake. At 30 s quantitative grain analysis of electron microscope autoradiographs showed predominant labeling of the plasma membrane and the smooth endoplasmic reticulum (SER). The grain distribution over the region of the plasma membrane decreased from 15% at 30 s to 7% by 300 s and was associated with a sevenfold increase in labeling of the Golgi apparatus and a sixfold increase in labeling of the pericanalicular region. Grain distribution over the SER at 300 s was the same as that noted at 30 s. The hypothesis is presented that bile acids move from the sinusoidal plasma membrane to bile via a pathway that includes the SER and Golgi apparatus.

Animals↗
PubMed1983

Protein-energy malnutrition and liver dysfunction limit the usefulness of the relative dose response (RDR) test for predicting vitamin A deficiency.

The relative dose response (RDR) test was examined for its value in predicting vitamin A nutriture among chronically ill patients with protein-energy malnutrition and among patients with varying degrees of liver dysfunction. The RDR test was elevated (ie greater than 14 per cent) and, thus, predictive of vitamin A deficiency in only 4 out of 9 patients with combined vitamin A deficiency and protein-energy malnutrition. Among 27 patients with liver dysfunction who had vitamin A determinations performed on liver biopsy material, there was no correlation found between the RDR response and the hepatic vitamin A level. Of 12 patients with low hepatic vitamin A levels (less than 100 micrograms/g wet weight), the RDR test was normal in 9 (75 per cent). Inability of the RDR test to predict vitamin A nutriture in patients with protein-energy malnutrition and in patients with liver dysfunction may, in part, be due to inadequate synthesis or release of retinol-binding protein.

Aged↗