Patients education: self-care guides.
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Biomedical subjects
Publications and source records attributed to M H Johnson.
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Uvomorulin (E-cadherin) is the major cell adhesion molecule responsible for intercellular adhesion in early mouse embryos. In contrast to other cell adhesion molecules, it is not detectable on the cell surface until around 6 h after fertilisation or parthenogenetic activation, at the time when pronuclear formation occurs (Clayton, L., Stinchcombe, S.V. and Johnson, M.H., Zygote 1, 333-44, 1993). In order to investigate this developmental control of surface expression of uvomorulin, we examined the effects of inhibitors of various cellular processes on the appearance of uvomorulin at the oocyte surface, as assessed immunocytochemically. Inhibitors of cytoskeletal assembly (cytochalasin D and nocodazole), protein synthesis (puromycin and anisomycin), and DNA synthesis (aphidicolin) had no effect on surface expression. Brefeldin A, which inhibits intracellular transport and secretion, did prevent surface expression, but monensin did not. The effects of brefeldin were reversible; following 8 h of treatment, recovery of surface expression after removal of brefeldin began within 2 h. The time-course of surface expression post-activation suggested a link with pronuclear formation. However, when pronuclear formation was advanced experimentally using 6-dimethylaminopurine (DMAP), concomitant advancement of surface uvomorulin was not observed. Similarly, surface expression of uvomorulin did not accompany puromycin-induced pronuclear formation in maturing meiotic metaphase 1 (MI) oocytes in vitro. Thus, surface uvomorulin expression does not appear to be linked simply to pronuclear formation. Proteolytic processing of both newly synthesised and total uvomorulin to generate mature molecule from precursor increased within 30 min to 1 h after activation, and also occurred in the continued presence of brefeldin, suggesting that uvomorulin processing appears to be controlled independently of its surface expression.
Human embryos were disaggregated into component blastomeres 42-72 h after insemination. The blastomeres were scored for the number of nuclei present and blastomeres of known nuclear morphology were returned to individual culture drops for 16-20 h, after which they were scored for cleavage and nuclear morphology. In all, 48% of mononucleated blastomeres cleaved during this period, but only 76% of these produced two mononucleated daughter blastomeres; in the remainder, one or more of the blastomeres was abnormally nucleated. During overnight culture, 30% of multinucleated blastomeres and 30% of anucleate blastomeres cleaved, the majority producing abnormally nucleated daughter blastomeres. The majority of blastomeres which showed no sign of cleavage after overnight culture retained the same nuclear morphology as when originally disaggregated. However, a small number of mononucleated blastomeres contained two nuclei after culture, indicating that karyokinesis may have taken place in the absence of cytokinesis. Overall, approximately 30% of blastomeres with more than one nucleus seemed to arise by this mechanism, the remainder probably arising by errors of chromosome segregation and/or packaging at mitosis. In addition, 25/111 mononucleated daughter cells arose either after abnormal division of mononucleated parent cells or after division of multinucleated cells, suggesting that approximately 23% of newly formed mononucleated cells might be chromosomally abnormal. The results of DNA quantitation indicated that very few (12/131, 9.2%) blastomeres (whether uni- or multinucleated) had a DNA content outside the 2-4C range. The embryos used for these studies had been cultured in one of three commonly used in-vitro fertilization (IVF) media: modified T6, Earle's balanced salts or Universal IVF medium (a commercial medium from Medi-Cult). A retrospective analysis was carried out of the number of embryos containing multinucleated blastomeres at disaggregation and of the total proportion of isolated blastomeres which were multinucleated in three groups of embryos, each of which had been cultured in one of the IVF media. Both these parameters were found to vary between cohorts of embryos cultured in the different media. The mechanism(s) by which culture medium composition might affect multinucleation of human blastomeres is discussed, as is the significance of these data for reliable preimplantation diagnosis of genetic status.
In the United States, 10,000 to 20,000 patients have epilepsy uncontrolled by medication. The addition of a second-line drug to the primary regimen has a 2% to 11% chance of controlling the seizures. We present a series of 35 patients with intractable epilepsy who had surgical resection of their seizure focus. Seventy-five percent of the patients with temporal lobe epilepsy were made seizure free, with an additional 14% sustaining a greater than 90% reduction in seizures (decrease in number and frequency). Seventy-one percent of the patients with extratemporal lobe epilepsy (seizures originating outside the temporal lobe) had a worthwhile reduction (> 90%) in their seizures. Two patients sustained permanent clinically significant deficits as a result of their presurgical evaluation or resection. There were no deaths. Epilepsy surgery offers a cure for the "incurable" patient with a morbidity of 5% to 6%.
It is difficult to tell a person that s/he has multiple sclerosis. The diagnosis is based on clinical findings and often cannot be made on first meeting. In many cases investigations do not help. When the diagnosis is made, the patient should be fully informed in the majority of cases. Guidelines have been developed for imparting the diagnosis. Early diagnosis will become increasingly important with the development of new treatments for multiple sclerosis.
To study the role of the metaphase spindle during the period of oocyte activation, mouse oocytes were fertilised or activated parthenogenetically in the presence or absence of the microtubule inhibitor nocodazole. In both cases, nocodazole caused the disappearance of the spindle and prevented the passage of the oocytes into interphase. However, the calcium spiking responses of the oocytes were not affected by nocodazole, being repetitive after fertilisation and a single spike after activation. If, after their activation or fertilisation in nocodazole, oocytes were later removed from the drug, only those that had been fertilised progressed into interphase. This progress was associated with continuing calcium spiking. Moreover, both the spiking and the progress to interphase could be blocked or reduced in incidence by removal of external calcium or addition of 5,5'-dimethyl BAPTA-AM. Oocytes that had been activated by ethanol in the presence of nocodazole and then removed from it, to allow re-formation of the spindle, only progressed into interphase if given a second exposure to ethanol, thereby eliciting a second calcium transient. These results show that exit from meiotic M-phase requires the simultaneous presence of a fully intact spindle during the release of calcium and that those factors leading to the degradation of cyclin B are only activated transiently. Since cyclin is being degraded continuously in the metaphase-II-arrested mouse oocyte and since this degradation is microtubule-dependent, these data suggest that the superimposition of a high concentration of intracellular calcium is required to tilt the equilibrium further in favour of cyclin degradation if exit from M-phase is to occur.
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PURPOSE: To demonstrate CT abnormalities encountered in children with postmeningitic deafness and to assess the value of CT in the prediction of cochlear implantation difficulties. METHODS: Thirteen children with postmeningitic deafness were evaluated with high-resolution, thin-section CT. CT findings were correlated with surgical anatomy at the time of cochlear implantation, with particular regard to the prediction of implant success. RESULTS: CT findings included normal scans (3 of 13, 23.1%), cochlear stenosis (5 of 13, 37.7%), cochlear fibroossific change (1 of 13, 7.7%), cochlear ossification (4 of 13, 30.8%), and osseous hypertrophy at the round window niche (4 of 13, 30.8%). Nine of 10 patients with abnormal findings had incomplete or difficult implantations (90%); 7 (88.8%) of these 9 received limited electrode insertions. CONCLUSION: Attention to subtle otological abnormalities on thin-section CT is helpful in the prediction of early success or failure of implantation in children with postmeningitic deafness. Those with CT abnormalities had a 90% risk of incomplete or difficult insertions with a 70% chance of limited electrode insertion.
We have obtained transgenic mice in which an erythropoietin-SV40 virus T antigen fusion gene is homologously recombined into the native Epo locus. This gene is expressed in a tissue-specific manner closely resembling that of the native Epo gene. Immunohistochemical detection of SV40 T antigen has been used to characterize the hepatic cell populations expressing the transgene. In mice stimulated by anaemia or hypobaric hypoxia, SV40 T antigen was demonstrated in two liver cell populations: a subset of hepatocytes and a nonparenchymal cell type. Immunohistochemical and ultrastructural characterization of these cells by light and electron microscopy showed the nonparenchymal cell type to be the Ito cells, which lie in a persinusoidal position within the space of Disse. We therefore conclude that Ito cells are the nonhepatocytic source of liver Epo production. These cells show many similarities to the Epo-producing fibroblastoid interstitial cells of the kidney.
The avian archistriatum has been demonstrated to play a role in agonistic behaviours and avoidance learning. However, the extent of its role in learning is unknown. The involvement of the archistriatum in the learning process of filial imprinting was therefore investigated in day-old chicks. Bilateral archistriatal lesions, lateral cerebral area lesions or sham archistriatal penetrations were made in dark-reared, day-old chicks, which were subsequently exposed to either a rotating red box or blue cylinder for 2 x 1 h training sessions. Three hours later, the approach of chicks to their training object and to the other, novel object was measured. Chicks with archistriatal lesions ran a similar distance towards each stimulus and therefore failed to display a preference for their training object. However, chicks with sham archistriatal penetrations or lateral cerebral area lesions exhibited a significant preference for the object they had been trained upon. These results demonstrate that the archistriatum is essential for the expression of an imprinted preference. All chicks approached their training object significantly more on their second compared to their first training exposure, suggesting that some aspects of imprinting behaviour remain intact in chicks with archistriatal lesions. Taken together with the results of previous work, the current data suggest that the archistriatum may be involved in retention of significant aspects of the imprinting experience, or in motivation to approach imprinting objects.
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A major obstacle to the study of mammalian development, and to the practical application of knowledge gained from it in the clinic during therapeutic in vitro fertilisation and embryo transfer (IVF-ET), is the propensity of embryos to become retarded or arrested during their culture in vitro. The precise developmental cell cycle in which embryos arrest or delay is characteristic for the species and coincides with the earliest period of embryonic gene expression. Much evidence reviewed here implicates free oxygen radicals (FORs) in the process of arrest. Thus, studies on the development of mouse preimplantation embryos in vitro have shown that (i) FORs are elevated in vitro, but not in vivo, at the time at which embryos become arrested or delayed, (ii) systems for removing reactive oxygen species to limit the formation of hydroxy radicals are present, although they have not yet been assessed quantitatively and may differ qualitatively from those in adult cells, (iii) metabolic and possibly genetic adaptations to oxidative damage are evident, (iv) published procedures for overcoming in vitro arrest are explicable in terms of FOR-mediated damage or responses and (v) the arrest or delay of most embryos in vitro can be reduced or prevented experimentally by addition of metal chelators to limit hydroxy radical formation and lipid hydroperoxidation.
Recent behavioral studies of infants have provided further evidence for the existence of cognitive and perceptual abilities in the first few months of life. Additional evidence from developmental neuroscience and comparative psychology has supported the view that, in some domains, such as visual attention and face and speech recognition, multiple neurocognitive processes give rise to the pattern of behavioral development observed over the first years of life. Primitive abilities and constraints present from birth may play an important role in facilitating the development of later-emerging processes that are more responsive to the effects of experience. In other domains, such as object permanence and memory, previous claims that the pattern of development was best accounted for by the sequential development of multiple neurocognitive systems have been brought into question.
Mouse oocytes were cryopreserved by a protocol shown previously to minimize damage to the zona pellucida and cytoskeletal system. After thawing, the incidence of fertilization did not differ from that in control groups of oocytes, and after fertilization, the ability of the fertilized frozen-thawed oocytes to develop to the blastocyst stage in vitro was only slightly less (77%) than that of the controls (87 and 89%). Transfer of frozen-thawed and fertilized oocytes after their culture to the blastocyst stage in vitro resulted in a lower implantation rate (46%) than for the controls (68-73%), but of the implanting embryos the same proportions in experimental and control groups survived to yield viable fetuses. In contrast, transfer after culture in vitro to the 2- to 4-cell stage resulted in similar implantation rates for control and frozen-thawed fertilized oocytes (70-84%), but the spontaneous abortion rate was higher for the embryos derived from frozen-thawed oocytes. Overall the cumulative survival rate for frozen oocytes transferred at the 2-cell stage (36%) was better than after transfer at the blastocyst stage (30%), but both were less than for the transfer at any stage of the control oocytes (47-55%). The cumulative survival of cryopreserved oocytes to viable fetuses was 30-40% less than that of the control oocytes. These results are compared with those from previous studies and the main remaining obstacles to completely successful cryopreservation are identified.
Using the polymerase chain reaction (PCR), amplification of two different target DNA sequences has been achieved with high frequency using single human blastomeres as template for the duplex reaction. One sequence is located within the beta-globin gene and contains the sickle cell locus, the other is a polymorphic dinucleotide repeat, which, as well as acting as a positive control for amplification, was used to check the origin of the amplified DNA. A comparison of the sequences amplified from the blastomere with sequences amplified from parental samples confirmed that amplification of blastomeric sequences, but not extraneous contaminating DNA, had taken place in most cases. The efficacy of this system for detecting extraneous DNA was checked by deliberately contaminating single blastomeres with foreign cells. The presence of contamination was detected by the amplification of sequences not present in blastomeric DNA and which therefore must have been amplified from extraneous contaminating DNA.
During the past 2 years, the staff in the Endoscopy Department at Georgetown University Hospital noticed an increase in the number of procedures being performed in the x-ray department. The nursing staff were becoming concerned with the amount of x-ray exposure they were receiving. The purpose of this article is to describe the process in which the nursing staff are equally rotated through radiology based on a daily log of fluoroscopy exposure for each nurse. At the completion of each x-ray procedure, the nurses chart the amount of x-ray and fluoroscopy exposure. Each nurse wears a total body film badge while a second badge is worn at the collar. Monthly dosimetry reports are made available for each nurse to review. After 1 year of monitoring by this method, it was found that fluoroscopy exposure was evenly distributed to each nurse.
Internal carotid artery (ICA) injuries including dissection, pseudoaneurysm, occlusion, and carotid-cavernous fistula (CCF) are well-recognized as potential consequences of blunt head trauma. We discuss a patient with a basal skull fracture and several types of carotid injury who was managed conservatively with excellent outcome.
The majority of cases of spinal canal compromise are caused by common pathologic conditions, including degenerative spondylosis, infection, trauma, and metastatic disease. However, there are other causes of spinal canal compromise that, though unusual, may be seen in everyday practice. Congenital abnormalities of the spine that may produce spinal canal compromise include the os odontoideum, hemivertebra, diastematomyelia, and achondroplasia. Arthritides and enthesopathies such as rheumatoid arthritis, ankylosing spondylitis, synovial cysts of the facet joint, calcium pyrophosphate dihydrate deposition or hydroxyapatite deposition, and ossification of the posterior longitudinal ligament or ligamentum flavum may lead to narrowing of the spinal canal. Primary spinal tumors and tumorlike lesions such as hemangioma, aneurysmal bone cysts, osteochondroma, and osteoblastoma may also cause spinal canal stenosis. Finally, Paget disease of bone may compromise the spinal cord. Radiologists should be aware of these unusual musculoskeletal causes of spinal canal compromise and their radiologic and clinical features.