Mediators: nitric oxide and other toxic oxygen species.
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Animals↗
Biomedical subjects
J Cohen
Publications and source records attributed to J Cohen.
Rotavirus subunit vaccines.
We evaluated rotavirus subunit vaccines for use in humans and animals. Insect cells were co-infected with combinations of individual baculovirus recombinants expressing human, bovine or simian rotavirus VP2, VP4, VP6 or VP7 to produce virus-like particles (VLPs). To determine whether immunization with VLPs could induce active protective immunity, VLPs were administered parenterally to rabbits, and the immune response and protection from rabbit ALA rotavirus challenge were evaluated. Complete or partial protection was attained, showing that parenteral immunization with VLPs induces active protective immunity. We also examined whether heterotypic immune responses could be induced with a limited number of broadly reactive VP7 proteins or with chimeric particles (multiple VP7 types on individual particles). The feasibility of this approach was determined by immunizing mice with VLPs containing a G3 VP7 or G1 VP7 and chimeric G1/G3 VLPs. Broadly reactive neutralizing antibody was induced by the G1 VLPs. VLPs also have been successfully used to boost lactogenic (colostral and milk) immunity in dairy cows. Taken together, these results show that VLPs can be effective immunogens in rabbits, mice and dairy cattle when administered parenterally, a limited number of VLPs may be sufficient to produce a broadly protective vaccine, and G3 VLPs may serve as an effective subunit vaccine for use in bovines.
Animals↗
Structure and function of rotavirus nonstructural protein NSP3.
The genomes of viruses in the family Reoviridae consist of segmented double-stranded RNA. There are 10 to 12 segments depending on the genus. The 5' ends and the 3' ends of the RNAs present conserved motifs for each virus genus. These conserved motifs have been hypothesized to play a role in genomic segment assortment during virus morphogenesis. Using a set of monoclonal antibodies we have tried to identify rotaviral proteins that bind to RNA during infection in cell culture. This methodology takes advantage of being able to label RNA in vitro to high specific activity and also of solid phase processing of RNA-protein complexes. After cross-linking the RNA to protein in infected cells, protein-RNA complexes are precipitated with a specific MAb; then, the RNA in the complex is labeled in vitro and the protein or nucleic acid moieties are analyzed by usual protocols. This paper describes results using an anti NSP3 MAb. In infected cells, we have shown that NSP3 binds to the eleven messenger RNAs, and that a sequence from nucleotides 8 to 15 is protected from digestion with RNAse T1 by NSP3 in the RNA-protein complex. The availability of recombinant protein NSP3 expressed in the baculovirus-insect cell system has allowed the sequence specificity of NSP3 to be studied in vitro. The minimal sequence recognized by NSP3 is GACC. The role of NSP3 in rotavirus replication is discussed based on these results and by comparison with other RNA-binding proteins of members of the Reoviridae family.
Animals↗
Prolactin concentrations in preterm and term pregnancy and labour.
Maternal plasma and amniotic fluid (AF) were obtained for measurement of prolactin concentrations from: 1) 20 patients with preterm labor and intact membranes who delivered within one week of amniocentesis; 2) 20 patients with preterm labor who responded to tocolysis and delivered at term; 3) 20 women at term who were not in labor and 4) from 20 women in active labor at term. No significant differences were found between: 1) maternal plasma prolactin concentrations in women with preterm labor who delivered prematurely and those who delivered at term (155 ng/ml vs 176.5 ng/ml); 2) patients at term who were not in labor (188 ng/ml) and those who were in labor (155 ng/ml); 3) AF prolactin concentrations in the two preterm labor groups (1987.5 vs 1282.5 ng/ml) and 4) AF prolactin concentration in the two term groups (562 ng/ml vs 701 ng/ml). Prolactin concentrations were generally significantly higher preterm than at term. We concluded that no significant changes in maternal plasma and amniotic fluid prolactin levels were found in preterm and term parturition.
Adult↗
Maternal plasma and amniotic fluid 17 beta-estradiol, progesterone and cortisol concentrations in women with successfully and unsuccessfully treated preterm labor.
Maternal plasma and amniotic fluid (AF) were obtained for measurement of 17 beta-estradiol, progesterone and cortisol concentrations from 40 patients with preterm labor and intact membranes at 28-32 weeks of gestation: 20 delivered preterm and the remaining 20 patients responded to tocolytic treatment and delivered at term. Maternal plasma and AF concentrations of these hormones were measured with specific commercially available radioimmunoassay kits. Maternal plasma and AF 17 beta-estradiol concentrations were significantly higher in women who delivered preterm than in those who delivered at term, 8.0 ng/ml vs 3.5 ng/ml and 0.85 ng/ml vs. 0.6 ng/ml, respectively. No significant differences were found between groups in maternal plasma and AF progesterone concentrations. Maternal plasma cortisol concentrations were higher in the preterm delivery group than in the term group (235 ng/ml vs. 55 ng/ml, respectively). No significant differences were found in AF cortisol concentrations between groups.
Adolescent↗
Maternal plasma and amniotic fluid dehydroepiandrosterone-sulfate concentrations in preterm labor and delivery.
The purpose of this study was to determine whether preterm parturition is associated with changes in maternal plasma and amniotic fluid dehydroepian-drosterone-sulfate concentrations. A cross sectional study was constructed according to the gestational age at admission and response to tocolysis. Group 1 consisted of women admitted with preterm labor and intact membranes between 28 and 31 weeks and 6 days gestational age (n = 40). Group 2 included 40 patients with preterm labor between 32 and 36 weeks gestational age. Both groups were classified into two subgroups: preterm delivery within seven days of admission and term delivery. Commercially available immunoassay kits validated for amniotic fluid analysis of DHEA-S, were used to measure maternal plasma and amniotic fluid DHEA-S concentrations. Maternal plasma DHEA-S concentrations were significantly higher in women with preterm labor who delivered preterm than in those who delivered at term. (Group 1: median 800 ng/ml [range 100-1100] vs. median 200 ng/ml [70-800], P < 0.001; Group 2: median 850 ng/ml [300-1700] vs. median 300 ng/ml [90-1100], P < 0.001). In contrast, no significant differences were detected in amniotic fluid DHEA-S concentrations. Our data suggest that the rise in maternal plasma DHEA-S concentrations observed in patients with preterm labor may be related to the effects of stress during labor.
Adult↗
Doctor James Young Simpson, Rabbi Abraham De Sola, and Genesis Chapter 3, verse 16.
When Dr. James Simpson began to use anesthesia in child-birth in 1846, a religious furor arose against its use. For many people, including many physicians, Genesis chapter 3, verse 16, implied that childbirth had to be a painful process. In 1849, the editors of one of Canada's medical journals asked Abraham De Sola, Canada's first rabbi, to give his interpretation of Genesis 3:16 for the benefit of their readers, which he did in a three-part article. Using Hebrew biblical scholars as his source, he wrote that the correct interpretation of this passage was that with toil or labor shall women bring forth children, rather than with pain. Therefore, by using anesthesia in childbirth, physicians were not going against the scriptures or the word of God.
Anesthesia, Obstetrical↗
Osmotic pressure probe of actin-myosin hydration changes during ATP hydrolysis.
Osmotic stress in the 0.5-5 x 10(6) dyne/cm2 range was used to perturb the hydration of actin-myosin-ATP intermediates during steady-state hydrolysis. Polyethylene glycol (PEG) (1000 to 4000 Da), in the 1 to 10 wt% range, which does not cause protein precipitation, did not significantly affect the apparent KM or the Vmax for MgATP hydrolysis by myosin subfragment 1 (S1) alone, nor did it affect the value for the phosphate burst. Consistent with the kinetic data, osmotic stress did not affect nucleotide-induced changes in the fluorescence intensities of S1 tryptophans or of fluorescein attached to Cys-707. The accessibility of the fluorescent ATP analog, epsilon ADP, to acrylamide quenching was also unchanged. These data suggest that none of the steps in the ATP hydrolysis cycle involve substantial hydration changes, which might occur for the opening or closing of the ATP site or of other crevices in the S1 structure. In contrast, KM for the interaction of S1.MgADP.Pi with actin decreased tenfold in this range of osmotic pressure, suggesting that formation of actin.S1.MgADP.Pi involves net dehydration of the proteins. The dehydration volume increases as the size of the PEG is increased, as expected for a surface-excluded osmolyte. The measured dehydration volume for the formation of actin.S1.MgADP.Pi was used to estimate the surface area of the binding interface. This estimate was consistent with the area determined from the atomic structures of actin and myosin, indicating that osmotic stress is a reliable probe of actin.myosin.ATP interactions. The approach developed here should be useful for determining osmotic stress and excluded volume effects in situ, which are much larger than those of typical in vitro conditions.
Actins↗
Low-dose inotropic stimulation during left ventricular ischaemia does not worsen post-ischaemic dysfunction.
OBJECTIVE: Inotropic agents are used clinically to improve ventricular function during ischaemia. The goal of this study was to determine whether inotropic stimulation during moderate left ventricular (LV) ischaemia exacerbated post-ischaemic LV dysfunction. METHODS: In 18 open-chest, anesthetized pigs, LV pressure versus subendocardial segment length loops were used to generate regional preload-recruitable stroke work (PRSW) and LV end-diastolic pressure (EDP) versus end-diastolic segment length (EDL) relations. Ischaemia was produced by constant, partial constriction of the mid anterior descending coronary artery for 90 min. Nine pigs received dobutamine (4 micrograms.kg-1.min-1, i.v.) during the final 60 min of ischaemia (Group 2), while 9 other pigs did not (Group 1). RESULTS: During unstimulated ischaemia, anterior subendocardial blood flow (Group 1, 0.27 +/- .05; Group 2, 0.30 +/- .07 ml.g-1.min.-1, mean +/- s.e.m.) and steady-state PRSW (Group 1, 30 +/- 4%; Group 2, 27 +/- 5% of baseline) were similar in both groups. Dobutamine stimulation during ischaemia increased heart rate, mean arterial pressure, subendocardial blood flow, oxygen consumption and steady-state PRSW of the ischaemia zone, but not lactate release. After 60 min reperfusion, steady-state ischaemic zone PRSW remained markedly and nearly equally reduced in both groups (Group 1, 28 +/- 4%; Group 2, 23 +/- 5% of baseline). Reduced PRSW after reperfusion was due primarily to persistent rightward shift of the PRSW intercept with only a modest contribution from reduced PRSW slope. CONCLUSIONS: Low-dose inotropic stimulation during moderate regional LV ischaemia increases aerobic, but not anaerobic energy metabolism, and does not worsen post-ischaemic dysfunction.
Animals↗
Intracytoplasmic sperm injection: a powerful tool to overcome fertilization failure.
OBJECTIVE: To describe the novel micromanipulation technique known as intracytoplasmic sperm injection (ICSI), which has been applied successfully to treat male factor infertility, even in patients with severely impaired sperm characteristics. This paper reviews the historical aspects that led to the development of ICSI in the animal model as well as the current experience in the human. DESIGN: Before using assisted fertilization techniques to enhance fertilization of human gametes, it is imperative that practitioners gain extensive experience in the animal model. In addition, criteria for accepting individuals for treatment with ICSI are discussed along with other applications of the procedure in infertile couples who do not benefit from standard IVF. RESULTS: Because ICSI resulted in limited success in animal models, it seemed unlikely that it would be successful in humans. Yet, ICSI now appears to be the most successful and significant innovation developed for dealing with male factor infertility since the emergence of IVF itself. To date, a relatively large group of healthy children have been born from this technology and there appears to be no increased incidence of congenital malformations. CONCLUSIONS: The consistently high success rate resulting from the application of ICSI to treat couples with male factor infertility is comparable to the results obtained using standard IVF techniques performed in nonmale factor couples. This finding indicates that spermatozoa obtained from subfertile men selected for intracytoplasmic injection are usually genotypically normal.
Animals↗
Pituitary apoplexy secondary to an underlying abscess.
An unusual case of pituitary apoplexy in a patient with pituitary abscess is described. The patient was found to have underlying chronic lymphocytic leukaemia and an associated hypogammaglobinaemia is postulated as being the predisposing cause for infection.
Abscess↗
Ten steps to create an innovative community-based pediatric experience as part of a clinical practicum: a model.
Innovative and alternative learning experiences are needed for students to obtain essential parts of the pediatric nursing clinical experience. This article presents a Ten Step approach guide for nurse educators to develop and implement a community-based pediatric primary health care model in a clinical practicum. The community pediatric primary health care experience is part of the San Jose State University School of Nursing's Nurse Managed Centers. Our approach focuses on providing community-based primary health care by faculty and nursing students to culturally diverse, underserved children and families in community settings in and around the university.
Child↗
Laparoscopy for the Acute Abdomen.
The application of laparoscopy for therapy is well established in biliary tract disease, inguinal herniorrhaphy, and fundoplication. Frequently, the diagnostic capability of laparoscopy is overlooked. A review of the literature and an institution's experience in laparoscopy for the acute abdomen is presented. Therapy was completed laparoscopically in a substantial number of cases.
Journal Article↗
Severe upper gastrointestinal tumor bleeding: endoscopic findings, treatment, and outcome.
BACKGROUND AND STUDY AIMS: The aim of the present study was to review endoscopic findings, treatment, and clinical outcomes in patients with severe upper gastrointestinal bleeding due to tumors. PATIENTS AND METHODS: A retrospective analysis was made of prospectively gathered data on all patients with severe upper gastrointestinal bleeding who were admitted to two large referral centers during a 45-month period. RESULTS: Nine hundred thirty-five patients had severe upper gastrointestinal bleeding, of whom 42 (5%) were found to have tumors. Histologically, nearly all of the tumors were of a malignant type. Fifty-two percent of the patients had acute severe upper gastrointestinal bleeding as the initial presentation of their tumor. The most common tumor was gastric adenocarcinoma, and all of these cases were at advanced stages. Endoscopic hemostasis with thermal probes or epinephrine injection, or both, was carried out in seven patients (17%), with successful hemostasis in all of the tumors. Regardless of the treatment given, patients with upper gastrointestinal tumor bleeding, had a 30-day surgery rate of 43%, a 30-day rebleed rate of 33%, a 30-day mortality rate of 10%, and a 1-year mortality rate of 89%. CONCLUSIONS: Most tumors that cause severe upper gastrointestinal bleeding are of a malignant histologic type and are already at an advanced stage. Endoscopic hemostasis of bleeding upper gastrointestinal tumors is safe and initially effective, and may provide time for elective surgical palliation. Regardless of therapy, upper gastrointestinal tumors with severe bleeding have a poor one-year survival.
Endoscopy, Digestive System↗
Invasive pneumococcal infections in human immunodeficiency virus-infected children.
Invasive pneumococcal infection (IPI) is the most common serious bacterial infection in human immunodeficiency virus (HIV)-infected children. Data from a population-based pediatric HIV surveillance project were used to determine the incidence of IPI in HIV-infected children and to conduct a case-control study assessing potential risk factors for IPI in HIV-infected children. There were 50 episodes of IPI and a cumulative incidence of 6.1 cases/100 patient-years through age 7 years. Children with IPI were more likely to have a prior AIDS diagnosis (odds ratio, 4.2; 95% confidence interval, 1.2-15.1) and higher levels of IgG and IgM (P=.01) than were controls. In a separate case-control study, the manifestations of IPI in HIV-infected children were compared with those in HIV-negative controls. Focal complication rates in the 2 groups did not differ; however, HIV-infected children were less likely than controls to have leukocytosis (P<.001) and more likely to have isolates with penicillin resistance (P=.03).
Age Factors↗
Streptococcal pyrogenic exotoxin A release, distribution, and role in a murine model of fasciitis and multiorgan failure due to Streptococcus pyogenes.
The role of streptococcal pyrogenic exotoxin A (SPEA) was evaluated in a murine model of fasciitis and multiorgan failure due to a toxigenic strain of Streptococcus pyogenes. Increased serum levels of SPEA at 15 and 21 h were associated with a survival time of <24 h. Levels of SPEA correlated with interleukin-6 levels. Immunostaining showed SPEA localized to renal and hepatic cells. Neutralizing rabbit antibody to SPEA was administered to mice challenged with S. pyogenes, but no effect on survival was observed. Vaccination of mice with recombinant SPEA enhanced mortality due to streptococcal infection, despite the development of neutralizing immunity to the toxin prior to infection. Hence, SPEA is produced systemically during S. pyogenes soft-tissue infection, and increased levels are associated with reduced survival. In this model, however, SPEA did not appear to play a dominant role in pathogenesis; passive immunization against SPEA was not protective, and active immunization enhanced mortality.
Animals↗
An audit of the use of antifungal agents.
The three month prospective audit of systemic antifungal therapy was undertaken in a university hospital in the United Kingdom to determine the patterns of usage of systemic antifungal drugs. The case notes of all patients receiving systemic antifungal agents were reviewed daily and the appropriateness of therapy was determined according to standards in the authoritative literature. One hundred and fifteen courses of treatment with antifungal agents for 1481 days were administered to 74 patients. When a patient has received more than one course of antifungals, both the individual courses and the combination of courses, i.e. a regimen, were judged. Antifungal agents were given as an empirical therapy or as prophylaxis in 68% of the courses, with fluconazole and amphotericin B desoxycholate being the agents most frequently used. Therapy was considered unconventional in 26.9% of the courses and 40.5% of the regimens, mainly because either the indication or the duration of treatment did not conform to conventional practice. Improvement in prescribing practices and standards for ongoing audit can only be achieved if a consensus can be reached on how these agents can be used appropriately.
Antifungal Agents↗
Oolemma characteristics in relation to survival and fertilization patterns of oocytes treated by intracytoplasmic sperm injection.
The aim of this study was to analyse the various reactions displayed by the oolemma to the penetrating pipette during intracytoplasmic sperm injection (ICSI) and correlate them with clinical factors, oocyte survival and fertilization patterns. Three types of oolemma responses were observed: normal breakage, when the injection needle created an invagination that ruptured at the approximate centre of the egg; sudden breakage, when the membrane broke without creating a funnel; and difficult breakage, when the membrane did not break or broke after several penetration attempts. A total of 2928 oocytes were analysed with the following observations: 73.9% (n = 2164) experienced normal breakage, 11.8% (n = 345) sudden breakage, and 14. 3% (n = 419) difficult breakage. The survival rate and number of normally fertilized oocytes were significantly lower and the incidence of digynic oocytes was significantly higher in the sudden breakage group; furthermore, in this group a significantly shorter length of stimulation was observed along with lower serum oestradiol concentrations when compared to oocytes experiencing normal and difficult breakage patterns. These recorded patterns were predictive of the survival and fertilization ability of the injected oocytes, as well as the incidence of digyny. The link between membrane behaviour and various clinical parameters appears to indicate a correlation between the modality of stimulation and oolemma characteristics.
Cell Membrane↗