Essential features of the pathway for protein translocation across the Escherichia coli cytoplasmic membrane.
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Alkaline Phosphatase↗
Biomedical subjects
C Murphy
Publications and source records attributed to C Murphy.
Perinatal nurse practitioners and health care reform.
Health care delivery for pregnant women at high risk is changing in response to the nation's need to contain costs and improve care. Perinatal nurse practitioners can provide specialized care to women at high risk in a wide variety of settings. They provide quality, cost-effective care and can improve access to prenatal care for families at risk for untoward pregnancy outcomes.
Curriculum↗
Photic headshaking in the horse: 7 cases.
Seven horses with headshaking are described. No physical abnormalities were detected in any of the cases. Six of these horses had onset of clinical signs in the spring. The role of light was assessed by application of a blindfold or dark grey lens to the eyes, covering the eyes with a face mask and observing the horse in total darkness outdoors. Cessation of headshaking was observed with blindfolding (5/5 horses), night darkness outdoors (4/4 horses) and use of grey lenses (2/3 horses). Outdoor behaviour suggested efforts to avoid light in 4/4 cases. The photic sneeze in man is suggested as a putative mechanism for equine headshaking. Five of 7 horses had improvement with cyproheptadine treatment (0.3 mg/kg bwt b.i.d.). Headshaking developed within 2 calendar weeks of the same date for 3 consecutive years in one horse. Neuropharmacological alterations associated with photoperiod mechanisms leading to optic trigeminal summation are suggested as possible reasons for spring onset of headshaking.
Animals↗
Stress-associated reductions of cytotoxic T lymphocytes and natural killer cells in asymptomatic HIV infection.
OBJECTIVE: Previous research has documented a possible relation of stress and depression to cell-mediated immunity. The authors examined how stressful events and depression may affect key parameters of cellular immunity in subjects with and without HIV infection. METHOD: Data were collected on 99 asymptomatic HIV-positive and 65 HIV-negative homosexual men as part of an ongoing, longitudinal study. Criticisms of previous studies of psychoimmunity were addressed by 1) using a comprehensive, semistructured interview to measure the objective context of stressful events, 2) double labeling of lymphocytes with monoclonal antibodies to measure subsets of cytotoxic/suppressor T lymphocytes and natural killer (NK) cells, and 3) controlling for circadian effects and methodological factors. RESULTS: In the HIV-positive men, severe stress was significantly associated with reductions in NK cell populations and a subset of T cells thought to represent cytotoxic T effector cells, particularly the CD8+ T cells expressing the CD57 antigen. In the HIV-negative men, no clear and consistent relation between stress and immune system measures was found. Depression was not correlated with any variables in either of the groups, perhaps due to the low levels of depressive symptoms. CONCLUSIONS: The findings suggest that stress is associated with reductions in killer lymphocytes (decreased NK cell and cytotoxic T lymphocyte phenotypes). The data provide evidence that stress may alter cell populations that provide cytotoxic defense against infection in HIV-positive men and indicate that the clinical significance of stress-related changes in cytotoxic T lymphocytes and NK cells in HIV infection warrants further study.
Adaptation, Psychological↗
Olfactory threshold and nasal mucosal changes in experimentally induced common cold.
Common cold is a most common disease in man accompanied by an experience of a diminished sense of smell. Controlled studies of the sense of smell are lacking and the cause as well as degree of impairment of smell in common cold has not been satisfactorily evaluated. We have investigated whether impaired olfactory ability accompanies common cold and if the loss is related to nasal blockage and to the amount of nasal discharge. For this purpose we measured the threshold of olfaction in volunteers before and after nasal inoculation with coronavirus 229E. The absolute olfactory threshold was assessed by a modified discrimination step test with dilutions of butanol. Symptoms of common cold were registered using a four-grade scale. Nasal obstruction was measured by nasal peak expiratory flow and by acoustic rhinometry and nasal discharge by weight of pre-weighted handkerchiefs. Individuals with a cold had impaired olfaction and the change in smelling ability correlated to the nasal congestion but not to the nasal discharge in analysis of multiple linear regression.
Adolescent↗
Trace element status and free radical defense in elderly rhesus macaques (Macaca mulatta) with macular drusen.
Research into the mechanisms underlying the development of age-related macular degeneration (AMD), the leading cause of visual loss in the United States and Europe in people over 60 years old, has been limited in part by the lack of animal models for this disease. In the current study, we examined 62 elderly (> or = 20 years old) rhesus macaques (Macaca mulatta) for the presence and severity of macular drusen. Drusen were observed in 47% of the macaques; they were similar histologically and in clinical appearance to the drusen observed in humans with AMD. It has been proposed that excessive tissue free radical damage may contribute to the development of AMD. Thus, circulating levels of select components of the free radical defense system and plasma thiobarbituric acid reactive substances (TBARS), an estimate of lipid peroxides, were measured in the above animals. Macaques diagnosed with drusen were characterized by alterations in concentrations and activities of several components of the free radical defense system. Alterations were most evident with respect to those enzymes associated with copper. The concept that excessive oxidative lipid damage might be a factor contributing to the occurrence of this disease is suggested by the findings of higher plasma TBARS concentrations in animals with > 10 drusen compared with animals without drusen.
Aged↗
Early removal of drains and discharge of breast cancer surgery patients: a controlled prospective clinical trial.
A prospective trial was conducted to see whether suction drains could safely be removed and patients discharged within 48 h of major breast surgery. Data from two consecutive groups of 50 patients each were compared. Statistical analysis confirmed demographic homogeneity between the two groups with regard to age, tumour size, lymph node involvement, grade of operating surgeon, procedures performed and the 48 h drainage volume. The first group of patients were discharged when drainage was considered acceptable (mean postoperative stay 4.5 days) (long stay). The second group had their drains removed and were discharged after 48 h (short stay). No seromas developed in either group when the total drainage volume (TDV) was less than 150 ml. Seromas developed in 3 (6%) of the long stay group and 5 (10%) of the short stay group (P > 0.05, chi 2 test). No seromas in either group required more than two aspirations. We conclude that it is safe to discharge patients after removal of drains on the 2nd postoperative day.
Adult↗
Quantification of the variation due to laboratory and physiologic sources in CD4 lymphocyte counts of clinically stable HIV-infected individuals.
We have conducted a study to quantify the amount of variation in the CD4 lymphocyte counts of HIV-infected individuals due to laboratory and physiological factors. Thirty HIV-infected male volunteers had blood drawn on six occasions: three times in each of 2 weeks, 4 weeks apart. Two tubes of blood were drawn at each visit, and duplicate measurements were obtained from one of the tubes of blood. Differences between duplicate measurements from a single tube of blood and between CD4 counts obtained from two tubes of blood drawn on the same day were attributed to laboratory factors. Differences between CD4 counts obtained on different days were attributed to a combination of laboratory factors and physiologic factors, which included the effects of exercise, tobacco, and the consumption of alcohol and caffeine. The mean absolute CD4 count at the first visit was 450 (range 86-1,081). The short-term coefficient of variation of CD4 count was 13.7 (95% CI: 12.9, 14.6). Physiologic and laboratory factors accounted for 85% and 15% of the variation in CD4 counts, respectively. Variation in the absolute white blood cell count, lymphocyte percentage, and CD4 percentage accounted fo 52%, 29%, and 19% of the physiologic variation in CD4 counts, respectively. Our results confirm a high degree of short-term variability of CD4 counts among HIV-infected individuals, which can be largely attributed to physiological factors. This variability can be minimized more effectively by repeating CD4 counts over time than by repeating measurements at a single visit.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Hypertensive emergencies.
Hypertensive emergencies are uncommon and physiologically diverse. Consequently, it is difficult for most physicians to develop a familiarity with all the different hypertensive crises and with all drugs available for treating them (Table 4). Clinicians should not agonize over which is the perfect therapeutic agent for a particular emergency, but instead, they should focus on scrupulous monitoring and familiarize themselves with a few agents that will serve in most situations. Generally, these agents will be sodium nitroprusside and nitroglycerin. Vigilant neurologic monitoring is mandatory in all hypertensive emergencies. The early symptoms and signs of cerebral hypoperfusion can be vague and subtle, but if recognized, serious complications of therapy can be avoided. Remember, the patient may still be hypertensive. Avoid acute (during the first hour) reductions in MAP of more than 20% whenever possible; subsequent reductions should be gradual. In patients known to have markedly elevated ICP and who need acute reductions in their BP, serious consideration should be given to direct monitoring of the ICP so that CPP can be maintained within safe limits. In general, oral agents should not be used for the treatment of hypertensive emergencies. Intravenous Labetalol and intravenous nicardipine are not suitable for general use in hypertensive emergencies. In special situations (e.g., perioperative hypertension and subarachnoid hemorrhage), however, they may be employed. Their role may expand with further study. Trimethaphan may be superior to nitroprusside for hypertension complicated by elevated ICP or cerebral dysfunction. Realistically, most physicians will continue to use nitroprusside. Intense neurologic monitoring is more important than the specific agent used. Nitroglycerin is the agent of choice for acute ischemic heart disease complicated by severe hypertension; if it fails, use nitroprusside. For aortic dissection, the combination of nitroprusside and IV propranolol is the therapy of choice; beta-blockade must be achieved rapidly or the dissection may worsen. Trimethaphan is also an agent for first-line therapy. Esmolol is an alternative to IV propranolol for the treatment of aortic dissection, if prolonged beta-blockade might seriously jeopardize the patient. For eclampsia, unless an expert in hypertension during pregnancy has established an alternative, the therapy of choice is hydralazine and magnesium. The treatment of subarachnoid hemorrhage is in flux; calcium channel blockers are used to prevent spasm, not to lower BP. If the BP must be lowered immediately, use nitroprusside.
Antihypertensive Agents↗
Smell impairment. Can it be reversed?
Patients who have lost the sense of smell usually come to a doctor on their own, reporting loss of the sense of taste. Inflammation (often due to allergy), viral infection, and head trauma are common causes of olfactory disturbance. History taking may provide clues to these and other problems (eg, toxin exposure, congenital dysosmia). Workup should not begin until a standardized test has been given that established impairment of the sense of smell. The only truly reversible cause is inflammation, which is confirmed when smell returns after a course of corticosteroid. Sinus computed tomography is necessary to view the olfactory cleft; lack of obstruction indicates that smell impairment is nonreversible. Patients deserve an explanation for their disorder and a prognosis. If restoration of their sense of smell is unlikely, patients should be cautioned to take steps to ensure safety in regard to such dangers as gas leaks, smoke, and spoiled foods.
Algorithms↗
Bilateral, perivulval cuticular pores in trichostrongylid nematodes.
A new hypodermal gland was discovered in female nematodes of the family Trichostrongylidae. Because the new structure appears to be associated with the vulva, it was named the perivulval pore. It is similar, based on light and scanning electron microscopy, to phasmids that are located laterally on the tails of nematodes of the class Secernentea. Like phasmids, perivulval pores are paired and bilateral, with cuticular ducts to the surface in the areas of the lateral chords. They are located slightly posterior to the vulva in Haemonchus contortus, Haemonchus placei, Haemonchus similis, Mecistocirrus digitatus, Mazamastrongylus pursglovei, Ostertagia ostertagi, and Cooperia oncophora, but in Trichostrongylus colubriformis they are slightly anterior to the vulva. Because of the location near the vulva and the similarity in structure to phasmids, which are, at least in part, secretory, the perivulval pores should be considered as a possible source of a female attractant for males.
Animals↗
Conflict resolution with end of life decisions in critical care settings.
This demonstration will present the key modules from an innovative videodisc-based program that was designed as an educational tool for health care professionals. It provides a resource for learning to deal with patients and families regarding the increasing problematic area of end-of-life-decisions. Tough Choices: Ethics, the Elderly, and Life-Sustaining Technologies is an interactive program that combines abstract ethical approaches with the realistic drama of a critical care setting. The format integrates scientific facts about the patient with value questions regarding the utilization of life-sustaining technologies. The unique program provides health care personnel with strategies on how to guide family decision-making as well as examples of the various interventions. This interactive multimedia program opens up an opportunity for health care providers to participate in a clinical case in which life and death decisions are made. Learners can explore various perspectives and treatment options within the framework of the dramatic case presentation without the usual time constraints or worries about causing harm to patients. The program involves learners in a variety of ethical and legal dilemmas that centers around a patient, her family, and a variety of health care professionals. Dramatic advances in the development of life-sustaining medical technologies have given hope to many people whose conditions would have meant certain death only a few years ago. As access to the technologies has expanded, concern for their appropriate utilization has become an issue worthy of increasing attention. Questions about the benefits of life-sustaining treatments are being raised in many quarters, particularly when the technology is viewed as a modern means of postponing death and prolonging suffering. Tough Choices brings to life the story of Irene Sullivan, an elderly widow who has an unexpected heart attack. Suddenly, her very existence depends on the life-support provided by mechanical ventilation and cardiopulmonary resuscitation (CPR). This is a growing area of concern since more than half of the patients who receive CPR and tube feedings and one third of the people receiving mechanical ventilation are 65 or over. Mrs. Sullivan's health care team is forced to deal with the opposing viewpoints of several close family members regarding the utilization of advanced medical technology. The interactive program invites viewers to explore the complex ethical and legal dilemmas involved in making life-and-death decisions about her care. It also permits immediate access to supportive resources in three areas: the clinical chart, abstracts of relevant research studies on life-sustaining technologies, and information from the professional literature on advance directives. The program incorporates practical steps involved in implementing the Patient Self-Determination Act as it follows the patient from the time of hospitalization through a series of life-threatening crises. Two very different aspects of the role of the health care professionals were explored: a crisis mode which covers the steps in managing a full-blown crisis situation, and a prevention mode which analyzes steps that could have been followed to keep an ethical crisis from occurring. The strong role models for practice display many of the characteristics that the helping professions need to foster in an atmosphere of healthcare reform.
Advance Directives↗
Identification of beta-trace as prostaglandin D synthase.
Human cerebrospinal fluid (CSF) is the richest source of prostaglandin (PG) D synthase, a key enzyme in sleep regulation, having a specific activity of 20-130 nmol/min/mg protein that is almost two orders of magnitude higher than that of crude rat brain homogenate (2-7 nmol/min/mg protein). PGD synthase was purified from human CSF approximately 8-fold to apparent homogeneity in a yield of 6% by ammonium sulfate fractionation followed by column chromatographies on phenyl-Sepharose and DEAE-cellulose. The purified enzyme displayed enzymatic properties almost identical to those of rat brain PGD synthase in terms of Mr, specific activity, optimum pH, Km value, and SH requirement. The purified PGD synthase cross-reacted with an antibody against rat brain PGD synthase and also with that against human beta-trace, a major protein in the CSF. Furthermore, beta-trace cross-reacted with rat brain PGD synthase antibody. The N-terminal sequences of human PGD synthase, beta-trace, and purified PGD synthase from human CSF were essentially identical. These results clearly show that beta-trace is structurally and enzymologically identical to PGD synthase.
Amino Acid Sequence↗
Chemical and serologic characterization of human lambda VIII light chains.
The primary structural features and serologic properties of a newly recognized human lambda light (L) chain V region subgroup (V lambda VIII) were elucidated through study of two monoclonal L chains, Bence Jones proteins HAG and BIV. The V region amino acid sequences of these components were highly homologous to each other and to that deduced from the prototypic V lambda VIII cDNA, Humla8f10, which encodes the L chains of the IgM lambda rheumatoid factor HAF10. Proteins HAG and BIV could be classified as members of the V lambda VIII subgroup and distinguished from L chains of the V lambda I, V lambda II, V lambda III, V lambda IV, and V lambda VI subgroups on the basis of amino acid sequence. In addition to distinctive residues found within the V lambda gene-encoded portion of the molecules, L chains HAG, BIV, and HAF10 contained remarkably different second complementarity-determining regions (CDR2) that consisted of 11 residues, rather than the seven typically found among members of the other five V lambda subgroups. This elongated structure would presumably impart to the ligand-binding site of lambda VIII molecules a markedly different canonical structure compared with those of lambda I, lambda II, lambda III, lambda IV, and lambda VI L chains. By using Bence Jones protein HAG as an immunogen, we obtained polyclonal and monoclonal anti-V lambda VIII subgroup-specific Abs that were used to identify and quantify lambda VIII-related molecules in normal and pathologic states. Among the Ig lambda components present in the serum of normal individuals, approximately 3% had lambda VIII L chains, a frequency comparable to that found among monoclonal Ig lambda proteins or surface(s) Ig lambda+ cells obtained from patients with malignant plasma cell- or B cell-related disorders, respectively. In contrast, lambda VIII L chains were detected on approximately 19% of monoclonal IgM lambda rheumatoid factors produced by B cell lines established from PBLs or synovial cells from patients with rheumatoid arthritis. The results of our studies provide new information on the structural and immunochemical features of lambda VIII L chains and the possible functional importance of the human V lambda VIII subgroup.
Amino Acid Sequence↗
Primary amyloidosis associated with a novel heavy-chain fragment (AH amyloidosis).
Primary or AL amyloidosis occurs in patients with monoclonal plasma cell-related disorders and is typically associated with the systemic deposition as amyloid fibrils of the light-chain portion of the immunoglobulin molecule. Recently, the discovery that heavy chains could be involved in amyloid formation led to the designation of this type of disease process as AH amyloidosis. We have now identified a second example of heavy chain-associated amyloidosis in a patient (MAD) who had a serum IgG monoclonal gammopathy and Bence Jones proteinuria. In this case, the renal and splenic amyloid deposits consisted solely of the VH-D-encoded portion of the heavy polypeptide chain, in contrast to the first case, where the amyloid contained an immunoglobulin component composed of the entire heavy-chain variable and third constant domains. In this respect, the chemical composition of the amyloid protein MAD differed not only from that of the first reported case of AH amyloidosis but from all other structurally abnormal components found in patients with heavy chain-associated disease. The discovery that certain forms of heavy chains, as well as light chains, can form amyloid provides further information on the chemical basis of amyloidogenicity and the diverse nature of this disease.
Amino Acid Sequence↗
Fetal liver length in diabetic pregnancy.
OBJECTIVES: Our purpose was to investigate whether liver size is increased in the fetuses of pregnant women with diabetes and whether there is any relationship between fetal liver size and maternal glycemic control. STUDY DESIGN: Eighty pregnant women with diabetes had ultrasonographic measurement of fetal liver length made at 18, 28, and 36 weeks' gestation. Twenty-four obese, nondiabetic women were studied at 36 weeks as controls. RESULTS: Fetal liver length measurements were significantly greater than normal by 18 weeks' gestation (12% above normal mean values; p < 0.001) and increased further (19%, p < 0.02) by 36 weeks. In the obese controls liver length was increased 9% and was significantly lower than in the diabetic subjects (p < 0.001). CONCLUSIONS: Fetal liver size in increased in pregnant women with diabetes and cannot be explained solely by maternal obesity. The major increase in liver size occurs early in pregnancy but appears to be modifiable by glycemic control later in gestation.
Adult↗
Human p80-coilin is targeted to sphere organelles in the amphibian germinal vesicle.
Cultured vertebrate cells often display one or more coiled bodies in their nuclei. These are spherical structures approximately 0.5-1.0 micron in diameter that contain high concentrations of small nuclear ribonucleoproteins (snRNPs); they are distinct from nuclear speckles and nucleoli, the other major sites of snRNP concentration. Coiled bodies in human cells contain a unique protein, p80-coilin, that has an M(r) = 80 kDa. Cloned p80-coilin cDNA encodes 576 amino acids with a calculated molecular weight of 62.6 kDa. To determine which of several snRNP-containing structures in the amphibian germinal vesicle (GV) might be the homologue of coiled bodies, we injected myc-tagged transcripts of full-length human p80-coilin into the cytoplasm of Xenopus oocytes and followed the fate of the translated proteins with an antibody specific for the tag. Western blots of GV proteins showed rapid appearance of both full-length and truncated p80-coilin in the nucleus. Immunofluorescent staining of spread GV contents demonstrated specific uptake of p80-coilin by the sphere organelle within 1 h after injection. Similar experiments were performed with a series of deletion constructs that lacked progressively longer segments from the carboxy terminus. A construct that contained only the first 102 amino acids (18% of the molecule) was specifically targeted to the sphere organelle. Conversely, a construct lacking the first 92 amino acids failed to localize, although it was imported into the GV. Thus, a relatively short region at the amino terminus of human p80-coilin is both necessary and sufficient for localization in the sphere organelle. Sphere organelles in the GV and coiled bodies in somatic nuclei are clearly related in composition. We suggest that they are homologous organelles with similar functions in preassembly and sorting of RNA processing components. Differences in their composition suggest functional specialization in the two cell types.
Amino Acid Sequence↗