Advanced certificate programs.
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Certification↗
Biomedical subjects
S Cook
Publications and source records attributed to S Cook.
Nursing and midwifery research: making it happen.
The organisation of a series of research awareness workshops for nurses and midwives in the North East Thames Regional Health Authority is described. The workshops, which aim to 'demystify' nursing research for practitioners, are particularly pertinent in view of government and nursing drives to raise the profile of research. Evaluations from workshop participants have shown a high degree of satisfaction with content and presentation.
Clinical Nursing Research↗
Formation of the perinuclear theca in spermatozoa of diverse mammalian species: relationship of the manchette and multiple band polypeptides.
The perinuclear theca is a novel cytoskeletal consisting of a densely layered lamina that surrounds the nucleus of mammalian sperm. Using antibodies specific for the multiple band polypeptides present in the perinuclear theca of bull sperm, we show that a heterogeneous group of immunological related proteins are present in the sperm heads of other mammals with greatly different morphologies, including guinea pig, hamster, rat, and mouse. In none of the species were identical groups of immunoreactive polypeptides found, although immunoreactive proteins of molecular weights 65,000 to 80,000 were present in the sperm heads of all species examined. Immunoreactive proteins less than Mr 55,000 were prominent in rat sperm heads and mouse sperm: guinea pig, hamster, and rat sperm heads and mouse sperm had one band in common at approximately Mr 50,000. Different immunoreactive proteins were present in isolated sperm tails. The perinuclear theca first appeared in the subacrosomal space of round to elongating spermatids. Later, with the caudal movement of the manchette, the postacrosomal segment of the perinuclear theca was deposited in a cephalad to caudal direction along the sperm nucleus. Concomitantly, the cytoplasmic space between the nuclear envelope and the plasma membrane narrowed such that only the theca occupied this portion of the sperm head. Immunoreactivity accompanied the ultrastructural appearance of the subacrosomal layer and the postacrosomal segment. The periods of spermiogenesis, in which sub- and post-acrosomal components of the perinuclear theca are formed and the morphogenesis of sperm organelles with which these elements are associated, suggest that components of this cytoskeletal structure function to join the acrosome and the postacrosomal plasma membrane to the nucleus.
Animals↗
Nascent protein requirement for completion of meiotic maturation and pronuclear development: examination of fertilized and A-23187-activated surf clam (Spisula solidissima) eggs.
The involvement of newly synthesized proteins and calcium in meiotic processes, sperm nuclear transformations, and pronuclear development was examined in emetine-treated, fertilized, and A-23187-activated Spisula eggs by observing changes in the morphogenesis of the maternal and paternal chromatin. Emetine treatment (50 micrograms/ml) initiated 30 min before fertilization or A-23187 activation inhibited incorporation of [3H]leucine into TCA-precipitable material and blocked second polar body formation. Sperm incorporation and the initial enlargement of the sperm nucleus were unaffected; however, the dramatic enlargement and transformation of the sperm nucleus into a male pronucleus, which normally follow polar body formation, were delayed 10 to 20 min. Unlike the situation in untreated, control eggs, male pronuclear development took place while the maternally derived chromosomes remained condensed. It was not until approximately 20 min after the normal period of pronuclear development that the maternal chromosomes dispersed and formed a female pronucleus in emetine-treated, fertilized eggs. Formation of pronuclei, however, was unaffected in both emetine-treated, A-23187-activated eggs and fertilized eggs incubated with A-23187. These observations indicate that germinal vesicle breakdown, first polar body formation, and initial transformations of the sperm nucleus are independent of newly synthesized proteins. Inhibition of second polar body formation and the delay in pronuclear development brought about by emetine, as well as the appearance of silver grains over pronuclei in autoradiographs of control eggs incubated with [3H]leucine demonstrate that nascent proteins are involved with the completion of meiotic maturation and the development of male and female pronuclei. The ability of A-23187 to override the inhibitory effects of emetine on pronuclear development suggests that both nascent protein and calcium signals are involved in regulating the status of the maternal and paternal chromatin during pronuclear development.
Animals↗
Pronuclear formation in starfish eggs inseminated at different stages of meiotic maturation: correlation of sperm nuclear transformations and activity of the maternal chromatin.
Changes in sperm nuclei incorporated into starfish, Asterina miniata, eggs inseminated at different stages of meiosis have been correlated with the progression of meiotic maturation. A single, uniform rate of sperm expansion characterized eggs inseminated at the completion of meiosis. In oocytes inseminated at metaphase I and II the sperm nucleus underwent an initial expansion at a rate comparable to that seen in eggs inseminated at the pronuclear stage. However, in oocytes inseminated at metaphase I, the sperm nucleus ceased expanding by meiosis II and condensed into chromosomes which persisted until the completion of meiotic maturation. Concomitant with the formation and expansion of the female pronucleus, sperm chromatin of oocytes inseminated at metaphase I enlarged and developed into male pronuclei. Condensation of the initially expanded sperm nucleus in oocytes inseminated at metaphase II was not observed. Instead, the enlarged sperm nucleus underwent a dramatic increase in expansion commensurate with that taking place with the maternal chromatin to form a female pronucleus. Fusion of the relatively large female pronucleus and a much smaller male pronucleus was observed in eggs fertilized at the completion of meiotic maturation. In oocytes inseminated at metaphase I and II, the male and female pronuclei, which were similar in size, migrated into juxtaposition, and as separate structures underwent prophase. The chromosomes in each pronucleus condensed, intermixed, and became aligned on the metaphase palate of the mitotic spindle in preparation for the first cleavage division. These observations demonstrate that the time of insemination with respect to the stage of meiotic maturation has a significant effect on sperm nuclear transformations and pronuclear morphogenesis.
Animals↗
Behavior-change strategies used by a sample of physicians for patients at risk of coronary problems.
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Behavior Therapy↗
Successful percutaneous extraction of a chronic left ventricular pacing lead.
This report describes a patient with a chronic endocardial left ventricular pacing lead. To avoid the risk of future embolization, it was felt that the lead should be removed and right ventricular pacing established. The lead was carefully evaluated by transesophageal echocardiography to exclude adherent thrombus. Successful percutaneous lead extraction was accomplished without sequelae, thus avoiding the morbidity of a thoracotomy.
Echocardiography↗
Prehospital cricothyrotomy in air medical transport: outcome.
In an attempt to determine outcome, this study reviewed the records of air medical patients undergoing prehospital cricothyrotomy (CRIC) from 1987 through 1989. The study included initial airway management, Trauma Score (TS) before and after CRIC and on arrival to the hospital, outcome, and initiator of airway--either emergency medical services (EMS) or LifeFlight air medical crew (LF). There were 68 CRIC in 3285 completed missions (2%). Patients averaged 31.4 years old with 46 males and 22 females. In rural environments, 60/68 patients were injured, with 65/68 injuries by blunt mechanisms. CRIC was performed by EMS in 24/68 patients and by LF in 44/68 patients. TS before CRIC, after CRIC, and on arrival to the hospital was not significantly different, averaging 5.8, 5.8, and 5.2. There were three complications of CRIC: two bleeds and one failure to insert. Five CRIC were changed to another airway at the receiving facility. Twenty-one out of 68 patients survived to discharge. There were no statistically significant differences in complications or overall mortality between LF and EMS CRIC. Prehospital CRIC appeared safe and complications were infrequent. The CRIC, once placed, remained the airway of choice in most patients. The eventual outcome in this population suggested serious injury with the majority of patients (69%) dying.
Adult↗
The effect of immunosuppression with whole body and regional irradiation on the development of cerebral oedema in a rat model of intracerebral haemorrhage.
A lesion simulating intracerebral haemorrhage was produced in the right caudate nucleus of rats immunosuppressed with whole body or regional irradiation. Whole body irradiation produced significant leucopaenia and thrombocytopaenia and conferred protection against cerebral ischaemia and oedema when compared to nonirradiated control animals. Local radiation to the head or torso did not confer protection.
Animals↗
Changes in blood lipids and lipoproteins in chronic alcoholics during alcohol withdrawal.
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Adult↗
Characterization of an acrosomal matrix protein in hamster and bovine spermatids and spermatozoa.
Experiments have been carried out characterizing an Mr 22,000 protein present in the acrosomes of hamster and bull spermatozoa. The Mr 22,000 protein is resistant to solubilization in detergent solutions containing high or low salt and has a pI of -5.2. With various lectins, the protein from hamster sperm was shown to be sparingly glycosylated with N-acetylglucosamine, mannose, and galactose while that from the bull demonstrated a slight reactivity for galactose. Using a specific monoclonal antibody (MAB 4/18), the Mr 22,000 polypeptide has been localized exclusively to the acrosomes of mature testicular and epididymal hamster and bovine sperm. Acrosomal components of differentiating bovine and hamster spermatids in tissue sections did not react with the monoclonal antibody, although the protein was present in immunoblots of round spermatids. In bovine sperm, MAB 4/18-staining at the ultrastructural level with immunogold-labeled second antibody was present as a reticulum throughout the acrosomal cap and as punctate aggregates in the equatorial segment. In hamster sperm, MAB 4/18-reactivity was present along the periphery of the acrosome in conjunction with matrix components (M1 and M2), as well as along the inner acrosomal membrane. These observations indicate that the acrosomes of bovine and hamster sperm possess an immunologically related Mr 22,000 protein and suggest that differences in MAB 4/18-staining of spermatids and spermatozoa is a result of epitope modification and/or a change in accessibility of the epitope to the antibody probe during the course of spermiogenesis. Based on its localization and solubility properties, we suggest that the Mr 22,000 protein, in conjunction with other polypeptides, forms a structural framework to maintain acrosomal shape and/or compartmentalize acrosomal contents.
Acrosome↗
Molecular mechanisms of sea-urchin sperm activation before fertilization.
Several mechanisms are used to control the behaviour of sea urchin spermatozoa while fertilizing eggs. These include discrete regulatory steps that modulate the sperm activation sequence from spawning to gamete membrane fusion. After release from the testis, sperm motility is instantaneously activated, by using intracellular pH as a throttle mechanism to control the rate of the dynein motor that catalyses axonemal bending. To support motility, energy is transported from the mitochondrion to the tail, by using a shuttle mechanism involving phosphocreatine diffusion. This shuttle employs a novel, endotriplicated, creatine kinase of Mr 140,000 in the flagellar axoneme as its terminus. The steering mechanism that determines where the spermatozoon swims is unknown, but may involve an egg peptide-induced guanylate cyclase activation, mediated by a cGMP-dependent Ca2+ channel, and attenuated by a plasma membrane cGMP phosphodiesterase. Upon arriving at the egg, which is identified by virtue of its proteoglycan coat (egg jelly), the spermatozoon undergoes a univesicular secretion that prepares it to fuse with the egg. This acrosome reaction involves several altered ionic fluxes in its mechanism, terminating in a massive Ca2+ uptake. If the spermatozoon is fortunate enough to fuse with an egg, a new member of the species is generated; if the acrosome reaction occurs without gamete fusion, the spermatozoon rapidly dies. All of these activation processes involve changes in the intracellular ionic milieu that are co-ordinated with altered enzyme activities, often in a causal fashion. Even with our current imperfect understanding of the process, a few of the steps in sperm activation may be defined by biochemical pathways that include specific modulatory control points.
Acrosome↗
Interventional cardiovascular therapy by laser and thermal angioplasty.
The advent of balloon angioplasty as a clinical device crystallized the concept of nonsurgical revascularization. The problems of restenosis, diffuse disease, and total occlusions persist despite the demonstrated efficacy of balloon angioplasty. During the past 5 years, a variety of laser devices and catheter designs have demonstrated usefulness in the treatment of peripheral vascular disease. Initial success rates of 70-90% have been reported in occluded femoropopliteal arteries. Further clinical trials are warranted to compare the relative efficacy of these devices with each other and conventional therapies. Thermal ablative devices have not yet shown great promise for treatment of coronary disease. Modified versions of these devices as well as nonthermally acting excimer lasers are promising as clinical tools for enhancing our ability to nonsurgically revascularize patients, and trials with these devices are now underway.
Angiography↗
Cytotoxicity of gelonin and its conjugates with antibodies is determined by the extent of their endocytosis.
Conjugates of the single-chain ribosome-inactivating protein gelonin with ligands that bind to cell surface molecules vary greatly in their cytotoxicity. Conjugates that are not endocytosed after binding to cells exhibit low cytotoxicity similar to that of free gelonin, while conjugates that are endocytosed demonstrate enhanced cytotoxicity relative to free gelonin. However, the number of internalized gelonin molecules needed to intoxicate cells to the same degree has been found to be similar for all conjugates and for free gelonin. The intracellular concentration of gelonin has to be between 2,000-10,000 molecules/cells to achieve a surviving fraction of 0.37. Our studies revealed the presence of three distinct categories of cell surface molecules, those that are efficient in mediating endocytosis of immunotoxins, those that are only moderately efficient, and those that seem not to cause internalization of bound immunotoxins.
Animals↗
Membrane specializations associated with the acrosomal complex of sea urchin sperm as revealed by immunocytochemistry and freeze fracture replication.
Observations, employing freeze fracture replication and electron microscopic immunochemistry, have been carried out to determine structural correlations of the plasma membrane domain occupied by a 210 kDa protein involved in the acrosomal reaction of sea urchin sperm and recognized by the monoclonal antibody, J10/14 (Trimmer et al.: Cell 40:697-703, 1985; Proceedings of the National Academy of Sciences of the United States of America 83: 9055-9059, 1986). Immunogold-J10/14 staining of acrosome-intact sperm was intense along the flagellum and a narrow collar just posterior to the sperm apex that surrounded the acrosomal complex (acrosomal vesicle and subjacent anterior nuclear fossa containing g-actin). Counts of gold particles revealed a density (average number of particles/micron2 of surface area) eightfold greater along the plasma membrane associated with the acrosomal complex than membrane delimiting the remainder of the sperm head. The collar of J10/14 staining was isomorphic with a dense aggregation of intramembranous particles in the P-face of the plasma membrane and a thin cytoplasmic region that surrounded the acrosomal complex. In acrosome-reacted sperm, intense J10/14 staining was distributed along the flagellum and sperm head; prominent anterior staining was not apparent in all specimens. The density of gold particles associated with plasma membrane delimiting components of the former acrosomal complex, nucleus and mitochondrion, as well as the total average number of particles along the entire sperm surface, were increased in sperm acrosome-reacted with A-23187. Concomitant with this change in staining was the disappearance/reduction of the collars of intramembranous particles and cytoplasm. These observations indicate that plasma membrane components (210 kDa protein and intramembranous particles) and the collar of cytoplasm which are associated with the acrosomal complex are functionally, as well as structurally related. Analyses of particle density distributions along acrosome- and non-acrosome-reacted sperm suggest that the different staining patterns observed may be brought about by the recognition of cryptic sites at the time of the acrosomal reaction.
Acrosome↗
Vertebral osteomyelitis due to Haemophilus aphrophilus: treatment with ceftriaxone.
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Adult↗
King's Fund Centre. Library & information services.
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Hospital Administration↗
Molecular orientation of immunoglobulin G at high concentration on an ion-exchange sorbent.
The change of molecular orientation of IgG, bound on a strong-anion-exchange surface, was studied using a generalization of the stoichiometric displacement model, over the entire range of protein adsorption isotherms. The Z number was found to decrease with increasing stationary phase protein concentration, approaching a limiting value. The analogy of the multiple equilibria model within highly cooperative identical binding sites was suggested as a possible way to evaluate the observed change in Z number with the protein concentration.
Adsorption↗