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The effects of phorbol myristate acetate and chemotactic peptide on transmembrane potentials and cytosolic free calcium in mature granulocytes evolve sequentially as the cells differentiate.

We isolated myeloid precursors from human marrow and studied the effects of phorbol myristate acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) upon transmembrane potentials and cytosolic calcium ([Ca2+]i) as the cells matured. Using a panel of fluorescent probes, we found that membrane depolarization induced by PMA and fMLP in granulocytes, and elevation in [Ca2+]i stimulated by fMLP, were absent in myeloblasts. When we induced differentiation with granulocyte-macrophage colony-stimulating factors, we found that both ionic responses appeared at approximately the promyelocyte stage. By using di-O-C5(3), we detected an initial phase of fMLP-induced hyperpolarization which appeared ontogenetically earlier than depolarization and which could be evoked in mature granulocytes with lower concentrations of the ligand. Hyperpolarization was partially dependent on extracellular Na+, was abrogated by increasing the external K+ concentration, and was accompanied by mild acidification of the cytoplasm. Bordetella pertussis toxin abolished both hyperpolarization and depolarization. Our findings indicate that shifts in [Ca2+]i and membrane potential changes in response to PMA and fMLP evolve as granulocytes mature. In addition, transmembrane ionic fluxes induced by fMLP appear to be more complex than previously considered, involving at least two separable phases of membrane potential change.

Aminoquinolines↗

Polypeptides of the oxygen-evolving photosystem II complex. Immunological detection and biogenesis.

Oxygen-evolving photosystem II complex was isolated from spinach chloroplasts. The individual polypeptides of the complex were isolated from sodium dodecyl sulfate (SDS)-polyacrylamide gels and antibodies were raised in rabbits against these polypeptides. After washing of the isolation complex by 0.8 M Tris to release the extrinsic proteins, a distinct diffused protein band was revealed at the position of 33 kDa in SDS gels containing 4 M urea. When this band was electroeluted from the gel and subsequently electrophoresed on SDS gels, three distinct protein bands became apparent. Antibodies raised against each one of these polypeptides cross-reacted with the other two polypeptides to varying degrees but not with the other subunits of the complex. The three polypeptides were denoted as "34," "33," and "32" kDa and the 33 being the herbicide-binding protein. Using the antibodies, the relative amounts of the photosystem II polypeptides were followed during greening of etiolated spinach seedlings. While all three extrinsic polypeptides were present in etiolated leaves at relatively high amounts, the other polypeptides could not be detected prior to an approximate 6-h illumination period. Further illumination induced the appearance of all of the rest of the subunits in a relatively similar rate. The oxygen evolution activity was developed parallel to the increase in the amounts of these polypeptides. Therefore, the assembly of the active photosystem II during greening is a two-step process in contrast with the photosystem I reaction center, which is assembled step by step, and the rest of the chloroplast protein complexes, which are assembled by a concerted mechanism.

Antibody Specificity↗

Comparison of the evolving histopathology of early and late cutaneous and asthmatic responses in rabbits after a single antigen challenge.

Histopathologic changes during the immediate cutaneous response (ICR) and late cutaneous response (LCR) to antigen challenge in allergic humans include dermal edema in the ICR (15 to 30 minutes) followed by increasing cellular infiltration in the LCR (6 hours and more). No description of the evolving histopathologic changes that occur during an immediate asthmatic response (IAR) followed by a late asthmatic response (LAR) exists in either clinical studies or animal models. We examined cutaneous and pulmonary histopathology at 1/2, 6, 24, and 48 hours as well as 7 days after simultaneous intradermal and aerosol antigen challenge of rabbits immunize with Alternaria tenuis extract. Nonimmunized rabbits challenged with Alternaria tenuis extract and immunized rabbits challenged with normal saline served as controls. Immediate wheal and flare responses followed by a LCR were seen in immunized but not control animals. Pulmonary function tests documented immediate and LAR in immunized but not control animals. Thirty minutes after antigen challenge of sensitized animals (ICR and IAR), both dermal sites and large airway submucosal sites had interstitial edema and vessel dilatation while small airways were essentially normal. At 6 hours after challenge, the dermal and large airway submucosal sites of immune animals (LCR and LAR) demonstrated a moderate mixed leukocyte infiltrate as well as residual edema. Additionally, bronchioles and pulmonary vessel adventitia from these responding animals had an intense and widespread leukocyte infiltration. At 24 and 48 hours, immune challenged animals but not controls had a marked mixed cellular infiltrate near skin vessels and near the bronchioles and pulmonary vessels with little or no residual interstitial edema. At 7 days, three of four animals showed resolution of the inflammation while the fourth showed minimal residual changes. Morphometric analysis of airway inflammation substantiated these qualitative observations and demonstrated that the granulocytes around airways of immune rabbits were a mixture of neutrophils and eosinophils at 6 hours, but were predominantly eosinophils at 48 hours. Immunofluorescent studies of skin and lung tissue did not demonstrate any granular or linear deposition of immunoglobulin or complement at the sites of inflammation, however, fibrin deposition was noted in the skin and lungs of immune rabbits. These observations show that immunized rabbits challenged with antigen develop cutaneous and pulmonary inflammation.(ABSTRACT TRUNCATED AT 400 WORDS)

Alternaria↗

Psychiatric home care. An evolving legal standard.

The treatment of mentally ill individuals in the home setting increases a psychiatrist's therapeutic responsibilities to the patient with commensurate greater legal exposure. Because psychiatric home care is in its infancy, the standard of care to be followed in implementing this therapy is still evolving. This article examines a psychiatrist's legal duties in providing home care as well as methods of practice to minimize allegations of inappropriate care.

Commitment of Persons with Psychiatric Disorders↗

Time course of effective interventional left heart assist for limitation of evolving myocardial infarction.

Previous work has shown that if pulsatile left atrial-femoral artery bypass is instituted after occlusion of the left anterior descending coronary artery for from 15 minutes to 2 hours, it can significantly limit the size of the infarct resulting 4 hours later. This study investigated whether pulsatile left atrial-femoral artery bypass begun after more clinically pertinent periods of initial ischemia can still significantly limit infarct expansion. After baseline measurements of hemodynamics, tension-time index, and regional myocardial blood flow in 73 open-chest, adult dogs, the left anterior descending coronary artery was ligated for 15 minutes or 1, 2, 4, or 6 hours of unprotected ischemia. In the five control groups, the initial ischemic period was merely extended for another 4 hours. In the five experimental groups, the animals were placed on pulsatile left atrial-femoral artery bypass for another 4 hours after the initial ischemic period. At the end of each procedure, gentian violet was used to identify the area at risk of infarction, and triphenyltetrazolium chloride was used to delineate the area of infarct. The results showed a significant reduction in the area of infarct as a percentage of the area at risk in each bypass group compared with its control group for all ischemic periods of less than 6 hours. These findings suggest that the maximum permissible ischemic time delay for myocardial salvage by pulsatile left atrial-femoral artery bypass is one which is pertinent in a clinical setting. The results justify continued attempts to develop appropriate techniques for percutaneous application of this modality to patients with an evolving myocardial infarction.

Animals↗

Emergency coronary artery reperfusion: a choice therapy for evolving myocardial infarction. Results in 339 patients.

Between 1975 and 1982, 339 patients underwent emergency coronary artery reperfusion for treatment of evolving myocardial infarction (MI). Group I (112 patients) had reperfusion with intracoronary streptokinase. Group II (46 patients) had reperfusion with a combination of intracoronary streptokinase and percutaneous transluminal coronary angioplasty (PTCA). Group III (181 patients) had saphenous vein bypass grafting. Twenty Group I patients and one Group II patient had emergency bypass grafting as streptokinase and PTCA were unsuccessful and significant myocardium remained at risk due to residual stenosis in the MI artery. Seventy-nine percent of Group III patients had successful thrombectomy of the infarcted artery, 33% of Group I had significant residual lesions after clot lysis, and 16% of Group I and 17% of Group III patients had no observable lesion on restudy. There were 10 early and two late deaths in the surgical patients. There were two deaths in Group I and no deaths in Group II. All deaths occurred in patients who were in cardiogenic shock before reperfusion (Group IV). Late follow-up (220 patients to 78 months) revealed three late MIs, four cerebral vascular accidents, two late cardiac and three noncardiac late deaths, and 31 patients with residual symptoms. Patients with an emerging MI should be treated via reperfusion of the MI vessel by one of these techniques. With single-vessel involvement, streptokinase lysis of the intercoronary thrombosis should be attempted. If this is successful and there is a significant residual stenotic lesion, the vessel should undergo balloon angioplasty at that time. If PTCA is unsuccessful, then bypass grafting should be done. When significant multiple-vessel disease exists in conjunction with an acute MI, the patient should have emergency saphenous vein bypass grafting as the treatment of choice.

Adult↗

Immediate coronary bypass following failed streptokinase infusion in evolving myocardial infarction.

Since December of 1980, 184 patients with evolving myocardial infarction (EMI) have undergone streptokinase infusion, with associated percutaneous transluminal coronary angioplasty (PTCA) in 68 patients. Emergency coronary bypass was deemed necessary in 24 of these patients. All 24 patients had severe triple-vessel disease and moderate to marked ventricular dysfunction, with eight (33%) requiring intra-aortic balloon pump (IABP) support for profound cardiac decompensation preoperatively. All 24 patients underwent immediate coronary bypass (average 4.1 grafts/patient), with four operative and two late deaths. Average postoperative blood loss was 1,453 ml, and average blood transfusion postoperatively was 8.2 units per patient. Thirteen patients had normal clotting studies immediately postoperatively, and only two patients developed frank coagulopathy (hyperfibrinolysis). Four patients required reexploration; two for coagulopathy, one for surgical bleeding, and one to rule out tamponade (negative). In those patients with EMI in whom streptokinase fails to result in adequate reperfusion, immediate emergency saphenous vein bypass grafting may be performed with reasonable morbidity and with acceptable hematologic consequences.

Adult↗

Complete sequence of the staphylococcal gene encoding protein A. A gene evolved through multiple duplications.

The gene coding for protein A from Staphylococcus aureus has been isolated by molecular cloning, and a subclone containing an 1.8-kilobase insert was found to give a functional protein A in Escherichia coli. The complete nucleotide sequence of the insert, including the structural gene and the 5' and 3' flanking sequences, has been determined. Starting from a TTG initiator codon, an open reading frame comprising 1527 nucleotides gives a preprotein of 509 amino acids and a predicted Mr = 58,703. The structural gene is flanked on both sides by palindromic structures followed by a stretch of T residues, suggesting transcriptional termination signals. Thus, it appears that protein A is translated from a monocistronic mRNA. The sequence reveals extensive internal homologies involving a 58-amino acid unit, responsible for IgG binding, repeated 5 times and an 8-amino acid unit, possibly responsible for binding to the cell wall of S. aureus, repeated 12 times. Comparisons between the repeated regions show a marked preference for silent mutations, indicating an evolutionary pressure to keep the amino acid sequence preserved. The structure of the gene also suggests how the gene has evolved.

Amino Acid Sequence↗

Acute evolving myocardial infarction. A surgical emergency.

This is a report of 342 cases of acute evolving myocardial infarction treated with prompt coronary artery bypass. Myocardial infarction results from a time-related sequence of ischemic pathophysiological changes. The first hours constitute a rapidly progressive event. Prompt surgical revascularization partially prevents impending myocardial necrosis; occasionally it may even prevent it completely. The results are limited infarct size, decreased mortality and morbidity, and a striking absence of the complications associated with conventional therapy (ventricular aneurysm or perforation and septal and papillary muscle rupture).

Adult↗

Evolving hypopituitarism in children with central nervous system lesions.

At the time children with suspected hypopituitarism are seen with a subnormal growth rate, it is expected that testing will demonstrate growth hormone (hGH) deficiency. Seven patients with organic CNS lesions--three with histiocytosis X, one with septo-optic dysplasia, one with neonatal meningitis, one with an anterior encephalocele and meningitis, and one with neurofibromatosis who had normal growth hormone concentrations (greater than 7 ng/mL) despite a subnormal growth rate--were studied. Subsequent retesting 0.5 to 4.6 years later demonstrated the development of growth hormone deficiency. Four of the patients had evidence of other pituitary hormone deficiencies at the time of initial testing whereas two subsequently developed other deficiencies. The initial subnormal growth rate in these children may be secondary to their organic CNS lesion or an evolving hypopituitarism, perhaps with deficient somatomedin generation. These studies point out the need for continued observation and retesting in such patients.

Age Determination by Skeleton↗

[Intracoronary thrombolysis as a treatment for evolving myocardial infarction].

Myocardial infarction is almost always the consequence of a thrombotic obstruction of one or more coronary arteries. We report our experience with the first 24 cases of intracoronary thrombolysis for recanalization of obstructed coronary arteries. 19 cases were successful, 1 case was partially successful and in 4 instances no reopening was observed. The amount of streptokinase used was 206 000 +/- 107 000 units, and reperfusion was achieved after 37 +/- 27.5 minutes. Recanalization of the vessel was accompanied by cessation of precordial pain and partial or complete normalization of the electrocardiogram. In one case bypass surgery was necessary because of reocclusion. Left ventricular function improvement after thrombolysis was dependent on the time-lag between occlusion and recanalization. These observations confirm others' experience that intracoronary thrombolysis appears to have favorable effects in patients with evolving myocardial infarction.

Coronary Disease↗

The joints of the evolving foot. Part III. The fossil evidence.

The fossil record supports the conclusions derived from the study of extant species that the Primates evolved a unique suite of characters in the articulations of the foot. The tarsal bones of African Miocene apes show specializations characteristic of hominoid evolution and provide reasonable precursors for the morphology of Pan, Gorilla and even Pongo. The OH8 foot is essentially ape-like in it major features, with many close resemblances to Pan. Although fairly clearly from a bipedal primate, it lacked important functional specializations found in the human foot.

Adaptation, Biological↗

Sequential histologic study of evolving lentigo maligna melanoma.

Malignant melanoma has been thought to evolve from junctional proliferation of atypical melanocytes, through a stage characterized by large junctional nests, into an invasive an ultimately metastasizing neoplasm. Sequential histologic study of a case of lentigo maligna melanoma suggested that the tumor progressed by development of more aggressive lesions in adjacent skin, rather than by evolution of preexisting lower-grade lesions. The higher grade of the later-developing lesions may result from greater exposure to carcinogens, perhaps by virtue of greater solar exposure prior to onset. Neural factors may be responsible for the progressive development of multi-centric lesions within a restricted region of skin (field effect). We recommend investigation of neurogenic influences in human melanoma, particularly with regard to the role of nerve growth factor.

Female↗

Phylogeny of NK cell reactivity against human and nonhuman primate lymphoblastoid cell lines: evolving and conserved target antigens.

Both human and nonhuman primate natural killer (NK) cells display little or no killing against allogeneic B lymphoblastoid cell lines. However, the same B cell lines are killed in baboon-human (B alpha H) or human-baboon (H alpha B) xenogeneic combinations. Competition-inhibition experiments indicate that the xenogeneic determinants recognized by NK cells are found principally if not exclusively on B rather than T target cells. Cell lines from closely related chimpanzee or orang-utan species can block some killing of human target cells, but lines from more distantly related species including gibbon, macaque, baboon, and marmoset do not inhibit cytotoxicity. This suggests that some NK target structures are susceptible to evolutionary change. Gibbon or marmoset lines infected with Epstein Barr virus (EBV) do not block killing, suggesting that host rather than viral determinants are being recognized. In contrast to the foregoing pattern, 2 cell lines derived from the same baboon differed in susceptibility to NK lysis irrespective of the effector cell species. The viral producer line 13CB-1 was more susceptible to lysis than its viral nonproducer partner 26CB-1. Thus, some NK target antigens may be highly conserved whereas others evolve with the species.

Animals↗

Immediate coronary artery bypass for acute evolving myocardial infarction.

Two hundred twenty-seven consecutive patients had chest pain and electrocardiographic, coronary angiographic, ventriculographic, and retrospective enzyme changes consistent with acute evolving myocardial infarction (AEMI). These patients underwent coronary artery bypass grafting an average of less than 6 hours after the start of chest pain. The mean age was 55.8 years (range 28 to 79 years). Sex, coronary artery involvement, and preoperative and postoperative enzymes and electrocardiograms are presented. Follow-up angiocardiograms done an average of 12.7 months postoperatively revealed 99 patent primary grafts in 102 patients (94.3%). Ejection fractions were normal, unchanged, or improved in 86.3% of the patients. Two ventricular aneurysms measuring less than 2.5 cm in diameter were noted. Surgical in-hospital mortality was 1.76% and first-year mortality was 1.44%. Conventional therapy in 200 AEMI patients treated at the same hospitals resulted in an in-hospital mortality of 11.5%. Follow-up of 213 patients having coronary artery bypass grafting revealed that 14% had mild angina. AEMI interrupted by coronary artery bypass grafting early in the syndrome yields results which are superior to conventional management.

Acute Disease↗

Surgery for evolving myocardial infarction.

One hundred fifty-six patients underwent emergency coronary revascularization during the early phases of evolving myocardial infarction (MI). There were six hospital deaths (3.8%) and two later deaths (1.3%). Thrombectomy of the MI artery was achieved in 79% of the patients, and 17% of the patients showed no observable lesion in the MI vessel on restudy. Graft patency was 99%. Late follow-up to 62 months disclosed 17 patients with residual limitations. Analysis of the data established criteria for recognizing patients with early MI who would benefit from surgical therapy. The criteria are derived by comparing preoperative and postoperative ventricular anatomy, creatine phosphokinase levels, and hemodynamics.

Clinical Enzyme Tests↗

The "limiting proximal gastric pouch": the evolving solution of morbid obesity.

Seventy-five patients received the "limiting proximal gastric pouch." The technique used is the complete transverse gastric stapling with Roux-en-Y reconstruction of gastrointestinal continuity. There was one death, 13 patients required rehospitalization, and five patients required reoperation because of complications. Both the weight loss and percentage of excess weight loss were satisfactory. The patients' acceptance was very high. The limiting proximal gastric pouch is evolving as the procedure of choice for morbid obesity.

Adult↗