Topological complexity of different populations of pBR322 as visualized by two-dimensional agarose gel electrophoresis

Neutral/neutral two-dimensional (2D) agarose gelelectrophoresis was used to investigate populations of the different topological conformations that pBR322 can adopt in vivo in bacterial cells as well as in Xenopus egg extracts. To help in interpretation and identification of all the different signals, undigested as well as DNA samples pretreated with DNase I, topoisomerase I and topoisomerase II were analyzed. The second dimension of the 2D gel system was run with or without ethidium bromide to account for any possible changes in the migration behavior of DNA molecules caused by intercalation of this planar agent. Finally, DNA samples were isolated from a recA-strain of Escherichia coli , as well as after direct labeling of the replication intermediates in extracts of Xenopus laevis eggs. Altogether, the results obtained demonstrated that 2D gels can be readily used to identify most of the complex topological populations that circular molecules can adopt in vivo in both bacteria and eukaryotic cells.     

Roles of estrogen receptor-alpha gene expression in reproduction-related behaviors in female mice

The role of gene expression of the estrogen receptor-alpha form (ER alpha) in the regulation of female reproductive behavior was investigated in estrogen receptor knockout (ERKO) mice, deficient specifically for the ER alpha, but not the ER beta, gene. Estrogen- or estrogen- plus progesterone-treated gonadectomized ERKO mice did not show any lordosis response. Detailed behavioral analysis revealed that ERKO females were also deficient in sexual behavioral interactions preceding the lordosis response. They were extremely rejective toward attempted mounts by stud male mice, which could not show any intromissions. During resident-intruder aggression tests, gonadally intact ERKO females were more aggressive toward female intruder mice than wild-type (WT) mice. Gonadectomy did not influence the levels of aggressive behavior, and their genotype differences when mice were tested both before and after gonadectomy. However, when mice were tested after gonadectomy for the first time, very few ERKO mice showed aggression. In contrast to aggression, male-type sexual behavior shown by resident mice toward female intruder mice during aggression tests was not different between ERKO and WT mice and was completely abolished after gonadectomy of the resident mice. Finally, it was also found that ERKO females showed greatly reduced levels of parental behavior toward newborn pups placed in their home cage. These changes in parental behavior were not influenced by gonadectomy. ERKO females retrieved significantly fewer numbers of pups with longer latencies compared with wild-type (WT) or heterozygous (HZ) littermates when they were tested as gonadally intact or 20-65 days after gonadectomy. In addition, during parental behavior tests, a significantly higher percentage of ERKO mice exhibited infanticide compared with WT and HZ mice, which rarely showed infanticide. Taken together, these findings suggest that ER alpha gene expression plays a key role in female mice, not only for sexual behavior but also for other interrelated behaviors, such as parental and aggressive behaviors. In addition, persistence of genotype differences in parental and aggressive behavior after gonadectomy indicates that ER alpha activation during neural developmental processes may also be involved in the regulation of these behaviors.     

Villoglandular adenocarcinoma of the cervix: cytologic presentation

A 69-year-old left-handed man developed Broca aphasia and jargon agraphia following a right cerebral infarction. He learned to write with his right hand. There is no family history of left-handedness. Neurological examination revealed hemiparesis, sensory impairment, and hyperreflexia with pathological reflexes on the left side. An MRI demonstrated lesions in the area including the pre- and post-central gyri, the posterior part of the middle and inferior frontal gyri, and inferior parietal lobule on the right side. Neuropsychologically he was alert and cooperative. He demonstrated severe Broca aphasia and his verbal output was limited to a few residual words. On the other hand, he could communicate through writing Kanji words. Writing words was relatively preserved with Kanji but not with Kana characters. Asked to write a Japanese folk tale, he showed jargon agraphia mixed with some correct Kanji words. His comprehension of spoken and written sentences was well preserved. He showed mild ideomotor and buccofacial apraxia, left unilateral spatial neglect, and constructional impairment. Dissociation between spoken and written language is a prominent feature of this patient's language output. In this patient, right hemisphere seems to be dominant for language and praxis, and left hemisphere for motor engram of writing. Learning to write with the right hand may have enhanced the establishment and maintenance of motor engram for writing in the left hemisphere. The intact motor engram of characters in the left hemisphere could be retrieved by the right hand without control from the language area in the diseased right hemisphere, resulting in jargon agraphia especially with Kana characters. In left handed people, the hand with which they learn to write may effect interhemisphere lateralization of language functions.     

A randomized, double-blind, placebo controlled comparison of droperidol, ondansetron, and metoclopramide for the prevention of vomiting following outpatient strabismus surgery in children

STUDY OBJECTIVE: To compare the efficacy of ondansetron, droperidol, or metoclopramide with placebo in preventing postoperative vomiting following strabismus surgery. STUDY DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: University outpatient surgery center. PATIENTS: 160 ASA physical status I and II children ages 1 to 12 years who were scheduled for strabismus surgery. INTERVENTIONS: Administration of either ondansetron 100 mcg/kg, metoclopramide 250 mcg/kg, droperidol 75 mcg/kg, or placebo intravenously after induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Both ondansetron and droperidol were superior to metoclopramide and placebo in preventing predischarge vomiting, with incidences of 5%, 5%, 32%, and 25%, respectively. However, there was no difference in the incidence of postdischarge vomiting among the groups (ondansetron 25%, droperidol 25%, metoclopramide 20%, and placebo 25%). CONCLUSIONS: While both ondansetron and droperidol are more effective than metoclopramide when compared with placebo in decreasing the incidence of predischarge vomiting, none of these drugs was more effective than placebo in decreasing the incidence of postdischarge vomiting. Recovery from anesthesia was not significantly different among the groups as assessed by time to awakening, initial Steward score, and time to discharge.     

Aspects of perinatal psychiatric illness

BACKGROUND: In view of the current changes in the National Health Service, it was considered an opportune time to review the literature on perinatal psychiatric illness. METHOD: A systematic review was undertaken of relevant articles on MEDLINE, ClinPsych and Excerpta Medica Psychiatry. RESULTS: Sixty-eight articles were used in the review. CONCLUSIONS: Developments in the field of perinatal psychiatry include a greater understanding of the nosology and aetiology of the conditions, the effect of maternal illness on the child, as well as transcultural factors. The perspective of the individual sufferer has been somewhat ignored. New treatments with both pharmacotherapy and hormones are emerging, but perhaps the greatest current challenge is to adapt our management strategies to community care.     

Raised ICP in a child with cryptococcal meningitis: CT evidence of a distal CSF block

Raised intracranial pressure (ICP) often complicates the course of cryptococcal meningitis. The pathogenesis of the severely raised cerebrospinal fluid (CSF) pressure commonly associated with this condition is largely unexplained, because the majority of patients have normal cranial computed tomographic (CT) findings when diagnosed. We report a case of cryptococcal meningitis in a child who had severely raised CSF pressure on admission, and in whom repeated CT scanning showed progressive enlargement of the subarachnoid space and ventricular system during the course of treatment. The normalization of these spaces after ventriculoperitoneal (VP) shunting suggests a distal CSF block as the cause of the raised ICP in this patient. The CSF pressure was monitored and treatment with oral acetazolamide and furosemide resulted in a definite, but slow and incomplete lowering of ICP. Intrathecal therapy with hyaluronidase had no beneficial effect on either ICP or the degree of visual loss.     

Comparison of Doppler US and CT angiography for evaluation of renal artery stenosis

RATIONALE AND OBJECTIVES: The authors compared Doppler ultrasound (US) with computed tomographic (CT) angiography in the evaluation of stenosis of the main renal artery. MATERIALS AND METHODS: Fifty-six patients who had undergone conventional angiography of the renal arteries participated in a prospective comparison of Doppler US (45 patients) and CT angiography (52 patients). US evaluation included both the main renal artery and segmental renal arteries. RESULTS: There were 27 main renal arteries with at least 50% stenosis in 20 patients. In 36 patients, there was no significant stenosis. All cases of main renal artery stenosis detected with Doppler US of the segmental arteries were also identified with Doppler US of the main renal artery. The by-artery sensitivity (63%) of US of the main renal artery was greater than that (33%) of US of the segmental arteries. CT angiography was more sensitive (96%) than Doppler US (63%) in the detection of stenosis, but the specificity of CT (88%) was similar to that of US (89%). The difference in the area under the receiver operating characteristic curve (AUC) between CT (AUC = 0.94) and US (AUC = 0.82) was statistically significant (P = .038). CONCLUSION: Doppler US of the main renal artery is more sensitive than Doppler US of segmental arteries in the detection of stenosis. CT angiography is more accurate than Doppler US in the evaluation of renal artery stenosis.     

Structure-activity relationship studies of novel carbocyclic influenza neuraminidase inhibitors

A series of influenza neuraminidase inhibitors with the cyclohexene scaffold containing lipophilic side chains have been synthesized and evaluated for influenza A and B neuraminidase inhibitory activity. The size and geometry of side chains have been modified systematically in order to investigate structure-activity relationships of this class of compounds. The X-ray crystal structures of several analogues complexed with neuraminidase revealed that the lipophilic side chains bound to the hydrophobic pocket consisted of Glu276, Ala246, Arg224, and Ile222 of the enzyme active site. The structure-activity relationship studies of this series have also demonstrated remarkably different inhibitory potency between influenza A and B neuraminidase. This indicated that the lipophilic side chains had quite different hydrophobic interactions with influenza A and B neuraminidase despite their complete homology in the active site. Influenza B neuraminidase appeared to be much more sensitive toward the increased steric bulkiness of inhibitors compared to influenza A neuraminidase. From the extensive structure-activity relationship investigation reported in this article, GS 4071 emerged as one of the most potent influenza neuraminidase inhibitors against both influenza A and B strains.