Search PubMed⌕ Search

Biomedical subjects

P Miller

Publications and source records attributed to P Miller.

At least 235 records · Page 13Linked to original sources
PubMed1987

Halothane anesthesia decreases human monocyte hydrogen peroxide generation. Protection of monocytes by activation with gamma interferon.

In an effort to determine the impact of halothane anesthesia on certain human cell-mediated immune functions, normal, purified human monocytes and lymphocytes were exposed to halothane in vitro at varying concentrations for up to 8 hours. Subsequently, these human effector cells were analyzed for their ability to function in several cell-mediated immunologic assays. Natural killer cell activity against K-562 was unaffected by halothane in most of the donors tested. Similarly, the ability of purified monocytes to inhibit MBL-2 tumor cell growth was unchanged. Halothane appeared to decrease the proliferative response of lymphocytes to phytohemagglutinin (PHA) in approximately 50% of the normal donors tested. In contrast, the ability of monocytes to lyse antibody-coated red cell targets (ADCC) was unaffected by even maximal exposure to halothane. Of interest was the finding that human monocytes exposed to as low as 2% halothane anesthesia for 4 hours displayed a dramatic down-regulation of hydrogen peroxide (H2O2) release. Since it is known that hydrogen peroxide and other incompletely reduced forms of oxygen secreted by monocytes can play a major role in the antimicrobial, antitumor, and inflammatory functions of these cells, this finding may help explain the enhanced susceptibility of post-operative patients to infections.

Adult↗
PubMed1986

Complete amino acid sequence of NADPH-cytochrome P-450 reductase from porcine hepatic microsomes.

The complete amino acid sequence of porcine hepatic microsomal NADPH-cytochrome P-450 reductase has been determined by microsequence analysis on several sets of proteolytic fragments. Sequence studies were performed initially on a 20-kilodalton (kDa) fragment and then on 80-kDa fragment. The amino-terminal end of the mature protein was blocked with an acetyl group, followed by 676 amino acid residues. It has been revealed that the COOH-terminal 20-kDa fragment has been derived from original enzyme by cleavage at the Asn-Gly (residues 502-503) linkage by an unknown mechanism. An NADPH-protected cysteine residue is located at residue 565, near a region exhibiting high sequence homology with ferredoxin-NADP+ reductase. The FMN and FAD binding regions are possibly located in the amino-terminal region and the middle part of the protein molecule, respectively, as suggested by Porter and Kasper [Porter, T. D., & Kasper, C. B. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 973-977]. When this sequence is compared with that of rat enzyme, 60 amino acid residues are substituted, probably due to species differences. However, total sequence homology between these enzymes is 90%. Hydropathy plot analysis reveals that two regions from residues 27-43 and from residues 523-544 exhibit a high degree of hydrophobicity, suggesting membrane binding or interaction with cytochrome P-450.

Amino Acid Sequence↗
PubMed1986

The effect of acute and chronic leukapheresis on the natural killer (NK) cell function of normal human volunteers.

Twenty-two normal volunteers had approximately eight, 2-hr-long leukapheresis procedures over a 2-year period and their natural killer (NK) cell function was prospectively measured. The NK activity of the preprocedure peripheral blood (pre-PB) was found to correlate well with the NK activity of the inital leukocytes removed by leukapheresis (I-Leuk). When the I-Leuk specimens were compared with the leukapheresis specimens removed at the termination of leukapheresis (T-Leuk), T-Leuk showed a consistent 10% increase in NK activity. When the pre-PB and the I-Leuk values were analyzed for each donor over the 2 years of the study, 18 donors revealed no significant change from their baseline NK activity, two donors showed a minimal increase in NK cell activity, and two donors displayed a minimal decrease in NK cell activity. We conclude that although leukapheresis appears acutely to boost NK cell activity, this increase is transient and small in magnitude. Most importantly, repeated leukapheresis does not appear adversely to effect this important effector function in normal donors.

Adolescent↗
PubMed1986

The natural history of traumatic branch renal artery injury.

Between 1979 and 1984, 24 patients with traumatic branch renal artery injuries documented by selective angiography were managed at our center. A total of 7 patients (29 per cent) died of nonurological organ system injury during the initial hospitalization. Of the remaining patients 10 were followed for 1 to 5 years after injury. None of these patients required immediate or delayed surgical intervention for complications, while 2 had hypertension after injury that resolved spontaneously by 1 year. The eventual renal function attained by these patients remained normal, the mean creatinine was 0.9 plus or minus 0.1 mg. per dl. and there were no other urological complications. Patients who sustain branch renal artery injuries should be managed nonoperatively unless they exhibit cardiovascular instability. Excision of ischemic parenchyma is indicated only when intractable hypertension associated with increased renin secretion can be identified.

Adolescent↗
PubMed1986

Inhibition of T3 mediated T-cell proliferation by Ca2+-channel blockers and inhibitors of Ca2+/phospholipid-dependent kinase.

The potential roles of Ca2+ ions in the response of T lymphocytes to stimulation with monoclonal antisera to the T3 antigen were investigated by means of pharmacological agents that predominantly inhibit the flux of Ca2+ ions into cells (verapamil, nifedipine) or the activity of Ca2+-dependent kinases (trifluoperazine, polymyxin B). As assessed by uptake of [3H]thymidine, proliferation induced with anti-T3 +/- recombinant IL-2 at 72 h was inhibited by greater than 80% in the presence of nifedipine at 50 microM, and almost completely arrested (greater than 95% inhibition) with the other agents at the same concentration. Further quantitative assays of the effects of polymyxin B and trifluoperazine on C-kinase labelling of exogenous substrate showed a major reduction with both agents, but inhibition was substantially greater with polymyxin B that with trifluoperazine (IC50 = 14 and 70 microM respectively). These results were confirmed by qualitative assessment of Ca2+/phospholipid-dependent phosphorylation of endogenous substrates, which demonstrated major phosphoproteins of MW 56,000, 52,000, 43,000, and 20,000, and dose-dependent reduction in labelling in the presence of polymyxin B. Similar results were obtained under more physiological conditions in intact cells labelled with 32P orthophosphate. These findings indicate several possible roles for Ca2+ in T-cell activation, and several possible levels of activity, including modulation of calmodulin-dependent kinases and effects on Ca2+/phospholipid-dependent kinases and Ca2+ channels.

Antibodies, Monoclonal↗
PubMed1986

Cholecystokinin mediates feedback regulation of pancreatic enzyme secretion in rats.

Previous studies have shown that trypsin and chymotrypsin in the duodenum exert a negative-feedback regulation on pancreatic enzyme secretion in the rat. The mechanism responsible for this physiological phenomenon is unknown. By use of a specific and sensitive bioassay based on amylase release from isolated pancreatic acini, the role of cholecystokinin in the negative-feedback regulation of exocrine pancreatic secretion was examined. Rats were prepared with duodenal cannulas and pancreaticobiliary cannulas. Diversion of pancreaticobiliary juice resulted in a threefold increase in pancreatic protein output and an increase of plasma cholecystokinin from a basal level of 0.5 +/- 0.08 pM cholecystokinin octapeptide (CCK-8) to 16 +/- 4 pM CCK-8. Perfusion of trypsin (2 mg/h) or pancreaticobiliary juice returned pancreatic protein output to basal levels and plasma cholecystokinin to 2.1 +/- 1.2 and 0.33 +/- 0.1 pM, respectively. The inhibitory effect of trypsin on cholecystokinin release was enzyme and site specific, since inhibition of cholecystokinin release was not observed with perfusion of amylase into the duodenum or with trypsin into the ileum. Intravenous infusion of proglumide abolished the increase in pancreatic secretion following diversion of pancreaticobiliary juice. Intraduodenal perfusion of lidocaine, infusion of tetrodotoxin into the superior mesenteric artery, or intravenous infusion of atropine inhibited the rise in plasma cholecystokinin seen with diversion of pancreaticobiliary juice. These studies suggest that feedback regulation of pancreatic enzyme secretion in the rat is mediated by release of cholecystokinin. Furthermore, the feedback mechanism is neurally mediated, involving a cholinergic pathway.

Animals↗
PubMed1986

Adoptive cellular immunotherapy of human ovarian carcinoma xenografts in nude mice.

Adoptive cell therapy with various purified populations of human lymphoid and monocytoid effector cells which have been in vitro activated with recombinant interleukin 2 and gamma-interferon was performed in an in vivo nude mouse model of human ovarian cancer. Administration i.p. of human interleukin 2-activated populations of large granular lymphocytes resulted in a significant extension of mean survival time (30 to 60 days) in this ovarian carcinoma model. In addition, T-cells activated with interleukin 2, in a similar fashion to large granular lymphocytes, also significantly prolonged survival of animals with ovarian carcinoma. In contrast, monocytes, with or without gamma-interferon activation, did not improve survival of tumor-bearing mice. In vitro results using direct isotopic release assays to measure efficacy of effectors against the ovarian cancer cells before and after activation, especially the activated natural killer cells, paralleled the effects on survival in the nude mouse model. However, the results with T-cells were somewhat inconsistent in vitro regarding their in vivo efficacy. We assume this is due to a delayed generation of activated killing in T-cells that is generated in vivo. These experimental results in this model system of human ovarian cancer indicate that transfer of autologous activated cells may have a role in the treatment of ovarian cancer patients.

Animals↗
PubMed1986

Life situations, health beliefs, and medical regimen adherence of patients with myocardial infarction.

One hundred twelve patients with MI were followed over a 6- to 9-month period to investigate their intentions and adherence behavior to a prescribed medical regimen in four life situations. The subjects with MI had strong intentions in the hospital to follow their prescription in all four situations, with the strongest for the home situation and the weakest for work. However, the actual adherence behaviors were less than the original intentions. The findings indicate the need for a review of the content of rehabilitation programs and consideration of the stage of recovery at which instructions are presented to patients rehabilitating from a MI. The intentions and adherence behaviors of subjects with MI were closely related to their perceptions of significant others' expectations. For the health team, this emphasizes the need to include significant others in patient rehabilitation.

Adult↗
PubMed1986

Evaluation of Coomassie dye binding method for microprotein assay in diabetic proteinuria.

A simple and relatively cheap method for quantitating diabetic microproteinuria with Coomassie brilliant blue dye binding method was evaluated. It provides a proportional reactivity to urinary albumin as measured by the more expensive immunoassay. The significant correlation between haemoglobin A1 and microproteinuria shows that the quantity of urinary protein is affected by metabolic control of diabetes.

Adult↗
PubMed1985

Amino acid sequence of COOH-terminal 20K Da fragment from pig liver microsomal NADPH-cytochrome P-450 reductase.

We have determined the complete amino acid sequence of a 20K Da COOH-terminal fragment of porcine NADPH-cytochrome P-450 reductase. The 20K Da fragment is probably produced by a proteolytic cleavage of the intact protein in porcine liver microsomes, and since the cleavage does not affect enzymatic activity, the fragment has been studied as a distinct domain. The sequence comprises 175 amino acids including three cysteine residues, one of which has been previously identified as protected by NADPH from S-carboxymethylation. The NADPH-protected cysteine lies in a stretch of 12 residues with partial homology to glutathione reductase, and is adjacent to a hydrophobic region containing a glycine-rich stretch homologous to other FAD-containing proteins. The predicted secondary structure over this entire region is beta-sheet/beta-turn/beta-sheet/alpha-helix/beta-sheet/beta-turn/alpha-h elix corresponding to hydrophobic residues 21-28/glycine-rich residues 29-33/residues 34-38/residues 39-54/residues 56-61/NADPH-protected cysteine residues 62-78/residues 71-82. It is possible that the 20K Da domain provided a significant portion of the sequence responsible for binding FAD and NADPH in the intact enzyme. This data provides a basis for further active site studies.

Amino Acid Sequence↗
PubMed1985

Functional differences between B cell-depletion techniques in removing memory B cells. Relevance to anti-erythrocyte autoantibody-specific suppressor cells.

The efficiency of a number of B cell-depletion techniques was examined in a functional assay. CBA (Iga) mice were primed with rat erythrocytes and their spleen cells transferred, before and after B cell depletion, to mice of the allotype-congenic strain Igb. The recipients were challenged with rat erythrocytes and their anti-erythrocyte autoantibody response was measured together with the donor (Iga) and host (Igb) anti-rat erythrocyte antibody levels. Transferred unseparated cells suppressed erythrocyte autoantibodies and produced high levels of anti-rat erythrocyte antibodies. Transfer of panned, rosetted or nylon wool-passaged cells neither altered donor anti-rat erythrocyte antibody levels nor abrogated suppression. By contrast, passage of rat erythrocyte-primed B cells over Ig-anti-Ig-coated beads resulted in removal of donor rat-primed B cell activity and loss of suppressor cells. The B cell-depletion techniques were effective at removing B cells as judged by the reduced number of fluoresceinated anti-Ig-labeled cells among unbound cells although analysis on a fluorescein-activated cell sorter revealed that the most effective method was depletion on Ig-anti-Ig-coated beads. B cell depletion by panning removed the capacity of virgin but not primed cells to make adoptive antibody responses after transfer suggesting that the primed cells most efficient in adoptive transfer have a lower density of surface Ig than virgin cells. Treatment of donors with drugs which abrogated transferrable suppression of erythrocyte autoantibodies did not alter donor anti-rat erythrocyte antibody levels in recipients. It is considered that rat primed B cells are involved in the suppression of erythrocyte autoantibodies by acting as selective antigen-presenting cells for T suppressor inducer cells, rather than through an anti-rat erythrocyte antibody feedback mechanism.

Animals↗
PubMed1985

Characterization of 3H-uridine incorporation and messenger RNA synthesis in human monocytes activated to secrete alpha interferon or monocyte-derived fibroblast growth factor.

Human monocytes are multifaceted cells with a wide range of immunoregulatory functions and distinct secretory products. This manuscript reports on initial attempts to identify specific early macromolecular synthetic events associated with various types of human monocyte activation by observing the patterns of RNA synthesis displayed by human monocytes that are exposed to well characterized activating stimuli. It was found that muramyl dipeptide (MDP), an activator of monocyte-derived fibroblast growth factor (MD-FGF) release from monocytes, also stimulates a reproducible increase in human monocyte total 3H-uridine incorporation and cytoplasmic messenger RNA (mRNA) synthesis at 4 h following activation. In contrast, polyriboinosinic acid:polyribocytidilic acid (poly I:C), an excellent stimulator of monocyte alpha interferon (IFN alpha) release, did not cause a change in either 3H-uridine incorporation or cytoplasmic mRNA production at any of the time points tested. Poly I:C was also found to be a poor stimulator of MD-FGF release. Conversely, MDP did not stimulate any detectable IFN release from human monocytes. The discrepancy between the patterns of macromolecular synthesis observed in human monocytes activated to secrete MD-FGF as compared with IFN indicates that divergent postactivation control mechanisms may be operative at the RNA level in the monocyte following activation of these two distinct functions.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1985

Plasma levels of apoprotein B in patients with diabetes mellitus: the effect of glycemic control.

Patients with diabetes mellitus often exhibit abnormalities in plasma lipoprotein concentrations. We have examined the effect of glycemic control (as assessed by hemoglobin A1 levels) on the concentrations of plasma lipoproteins and apoproteins in 109 patients with type I diabetes mellitus. HbA1 levels showed positive correlations with plasma LDL-cholesterol levels (r = 0.31; P less than 0.002) and triglyceride levels (r = 0.41; P less than 0.002), but not with HDL-cholesterol levels. The strongest correlation was between HbA1 and plasma levels of apoprotein B (r = 0.57; P less than 0.001). We have also examined the effect of long-term improvement in glycemic control (achieved with insulin infusion pump therapy) on plasma lipoproteins in six patients with type I diabetes. Patients were followed for 5 to 12 months, with mean (+/- SD) HbA1c levels decreasing from 11.4 +/- 2.5 to 9.1 +/- 1.8. Most, but not all, patients showed reduction in plasma LDL-cholesterol levels and increase in plasma HDL-cholesterol levels, but these did not reach statistical significance. Only the decrease in plasma apo B levels was statistically significant (from 112 +/- 38 mg/dL before pump therapy to 91 +/- 33 mg/dL at the end of the follow-up, P less than 0.05). We conclude that glycemic control plays an important role in regulating the levels of plasma LDL-cholesterol and triglycerides in patients with type I diabetes. Apoprotein B is a particularly sensitive indicator to alterations in glycemic control. It is possible that tight glycemic control may have "antiatherogenic" effects through reduction of apo B levels.

Adolescent↗