Nuclear magnetic resonance methods to study structure and dynamics of RNA-protein complexes.
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Biomedical subjects
Publications and source records attributed to M Allen.
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The purpose of the study was to describe the results of follow up of human contacts of bovine tuberculosis. The bovine tuberculosis cases occurred on farms in North Staffordshire between 1993 and 1997. A total of 162 people were identified as having close contact with cattle diagnosed as having bovine tuberculosis, or who had drunk unpasteurized milk from a herd with bovine tuberculosis. A retrospective review of chest clinic notes was performed. One hundred and thirty-eight people attended for follow up, and Heaf test results, necessity for chest X-ray and further clinical follow-up are described. No case of human Mycobacterium bovis infection was identified. It is suggested that follow-up of human contacts is limited to those with close contact with herds who have bovine tuberculosis and cattle with visible pulmonary lesions or evidence of udder infection. Children on the farms with affected cattle should also be offered BCG in advance of the routine school's programme.
SUMMARY: Corneodesmosin (Cdsn) is a late differentiation epidermal glycoprotein putatively involved in keratinocyte adhesion. The Cdsn gene lies within the susceptibility region on chromosome 6p21.3 (PSORS1) for psoriasis, a common chronic disfiguring skin disease. A particular allelic variant of Cdsn has a strong association with psoriasis. Therefore, genetically and biologically, Cdsn is a possible candidate gene for psoriasis susceptibility. To investigate a potential role for Cdsn in psoriasis pathogenesis, protein expression studies were performed by quantitative immunohistochemistry on normal skin, psoriatic skin (lesional and nonlesional), and other skin disorders using monoclonal antibodies (G36-19 and F28-27). In normal and nonlesional skin, Cdsn was expressed in stratum corneum and one or two layers of superficial stratum granulosum. In lesional psoriasis, there was a significant increase in Cdsn expression, which was observed in multiple layers of stratum spinosum and in stratum corneum. The expression pattern varied from granular, cytoplasmic immunoreactivity to cell surface labeling with weakly immunoreactive cytoplasm. In chronic atopic dermatitis, lichen planus, mycosis fungoides, and pityriasis rubra pilaris, Cdsn immunoreactivity was confined to stratum corneum and upper stratum granulosum with no stratum spinosum immunoreactivity. Immunoelectron microscopy of normal and lesional psoriatic skin demonstrated Cdsn release concomitant with involucrin incorporation into cell envelopes and completed before mature envelope formation. Extracellular release of Cdsn occurred at a lower level of the epidermis in psoriasis than normal skin. These protein expression studies provide evidence of altered Cdsn expression in psoriasis consistent with a role of Cdsn in disease pathogenesis. Further functional and genetic studies of Cdsn are justified to determine its role as a potential psoriasis-susceptibility factor.
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A case of fetus in fetu was diagnosed prenatally using ultrasound. The differential diagnosis between a fetus in fetu and a highly differentiated teratoma is discussed. The importance of prenatal diagnosis of fetus in fetu and the effect on subsequent management are described.
After a motorcycle accident, a 22-year-old male was diagnosed with multiple rib fractures, left-sided tension pneumothorax, hemothorax and left upper lobe bronchus rupture at its origin. An emergency left thoracotomy revealed an almost complete avulsion of the upper lobe bronchus from the main stem bronchus, a severely damaged pulmonary artery, and a concurrent deep intraparenchymal lower lobe laceration. Since the patient was hemodynamically stable, a decision was made to preserve as much lung as possible. In the event of complex pulmonary trauma, pulmonary preservation is desirable since emergency pneumonectomy is usually associated with high mortality. Early bronchoscopic assessment, careful anesthetic management, and meticulous surgical technique with liberal use of fibrin glue were crucial to successful outcome.
BACKGROUND: Preoperative identification of lymph node metastases associated with esophageal carcinoma may influence treatment. EUS is the most accurate method for locoregional staging of these tumors. The impact of EUS-guided fine-needle aspiration (EUS-FNA) on lymph node staging in esophageal carcinoma is unclear. METHODS: From May 1996 to May 1999, 74 patients with esophageal carcinoma underwent preoperative EUS. After October 1998 EUS-guided FNA was performed on nonperitumoral lymph nodes greater than 5 mm in width. The results of EUS with and without FNA were retrospectively reviewed and compared. Final diagnosis was based on surgical results or EUS-guided FNA malignant cytology. Ten of the 74 patients had to be excluded for lack of lymph node stage confirmation. Final diagnosis was obtained in the remaining 64 patients (33 from the EUS only group and 31 from the EUS-FNA group). RESULTS: The results of EUS versus EUS-FNA for lymph node staging were sensitivity 63% versus 93% (p = 0.01), specificity 81% versus 100% (not significant), and accuracy 70% versus 93% (p = 0.02), respectively. Complications comprised 1 patient who developed self-limited bleeding after dilation that did not preclude completion of the EUS (1%, 95% CI [0%, 7%]). CONCLUSIONS: EUS-FNA is more sensitive and accurate than EUS alone for preoperative staging of locoregional and celiac lymph nodes associated with esophageal carcinoma. EUS-FNA of nonperitumoral lymph nodes in patients with esophageal carcinoma is safe and should be routinely performed when treatment decisions will be affected by nodal stage.
OBJECTIVE: Our hypothesis was that the degree of antenatally diagnosed cerebral ventriculomegaly is related to aneuploidy, perinatal mortality and long-term neurological morbidity. METHODS: Ninety-one cases of ventriculomegaly identified from 1 June 1994 to 1 July 1999 were examined for prenatal, intrapartum and neonatal complications. Pediatric follow-up was reviewed for infants with ventriculomegaly from birth up to as long as 4 years. Minor neurological morbidity was defined as a score of 70-80 on the clinical adaptive test/clinical linguistic and auditory milestone scale and included mild motor or language delay. Major morbidity included a score of < 70, evidence of cerebral palsy, or seizure disorder. The incidence of neurological complications was compared, on the basis of the degree of ventriculomegaly, with group 1 being > 10-15 mm and group 2 being > 15 mm. RESULTS: Twenty-seven cases (18 with neural tube defects and nine with holoprosencephaly) were excluded. Among the remaining 64 patients, 39 had a ventricular diameter of > 10-15 mm and comprised group 1. Five of the 39 cases (12.8%), all with other ultrasound anomalies, elected to terminate. The incidence of aneuploidy in group 1 was 14.2%. Among the 19 cases with isolated ventriculomegaly, 17 (89%) were normal and two (11%) had minor neurological morbidity. In group 1 there were two cases associated with cytomegalovirus (CMV) infection. Of the 25 cases in group 2, eight (32%), all with other ultrasound anomalies, elected to terminate. The incidence of aneuploidy in group 2 was 17.4%. For the nine cases with isolated ventriculomegaly of > 15 mm, one (11%) was normal (p < 0.001), five (56%) had minor neurological morbidity requiring a ventriculoperitoneal shunt (p = 0.035), and three (33%) had major neurological morbidity (p = 0.045) when compared to cases of isolated ventriculomegaly in group 1. There was one case of CMV infection in group 2. All perinatal deaths in both groups were associated with other anomalies. CONCLUSIONS: Amniocentesis to determine karyotype and the presence of CMV is warranted for all cases of ventriculomegaly of > 10 mm. The degree of antenatal ventriculomegaly is related to pediatric neurological morbidity and, when it is > 15 mm, it is associated with an increase in abnormal neurological development.
Many polynuclear aromatic hydrocarbons (PAHs) are either known or suspected carcinogens and are a common constituent of mineral oils. Due to the large number of possible PAH structures, standard quantification methods fail since they either lack specificity or are too complex, requiring individual fractionation, identification, and quantification. A rapid, low-cost, novel analytical screening method, incorporating a silica-based solid-phase extraction (SPE) method linked to co-solvent dilution and quantification of total and carcinogenic PAH levels by immunoassay, is reported here. The method yielded high extraction efficiencies and minimal matrix effects. This novel approach yielded total and carcinogenic PAH levels x 5.7 and x 126, respectively, lower than that recorded by the industry-recognised BS2000 Pt. 346 (IP346) method which estimates the polyaromatic carbon (PAC) content of oils by gravimetry. The method is expected to be of benefit where an indication of PAH levels in oils is important for purchasing, management or disposal purposes and also for risk assessment and for appropriate labelling of oils in line with current legislation.
BACKGROUND: Stage at diagnosis has been used to compare the quality of cancer screening services by health insurance type, using membership at diagnosis or treatment. This study evaluates breast cancer stage among women on Medi-Cal, California's Medicaid program, in relation to duration of coverage to assess the impact of including women with recently acquired benefits in the Medi-Cal group. METHODS: Breast cancers diagnosed in 1993 among women ages 30 to 64 were obtained from the statewide, population-based cancer registry and linked to Medi-Cal enrollment files. Women on Medi-Cal when diagnosed were categorized based on months covered during the 12 months preceding diagnosis (12, 1-11, or none), and compared with all other women with breast cancer. Logistic regression models measured the effect of duration of Medi-Cal coverage on the odds of late-stage disease, controlling for demographic, socioeconomic, health access, and tumor characteristics. RESULTS: Among women with Medi-Cal benefits when diagnosed, 18% were not covered during the year preceding diagnosis, and late-stage disease was common among these women. The odds ratio for late-stage disease among all women on Medi-Cal was 1.67 (95% CI 1.41, 1.97), but was reduced by 42% to 1.39 (95% CI 1.15, 1.67) when women without benefits before diagnosis were excluded from the Medi-Cal group. CONCLUSIONS: Women with Medi-Cal benefits before diagnosis were more likely to be diagnosed with late-stage disease than other women with breast cancer. However, the practice of assigning health insurance status based on enrollment at diagnosis underestimates the effect of access to breast cancer screening through Medicaid.
Policy makers have recently begun to reconsider involuntary outpatient commitment as a means of enhancing public safety and providing mental health services to people deemed to be noncompliant with treatment. The authors review the therapeutic claims for outpatient commitment and take the position that there is insufficient evidence that it is effective. They offer arguments that outpatient commitment may not improve public safety and may not be more effective than voluntary services. The authors further point out that outpatient commitment may undermine the delivery of voluntary services and may drive consumers away from the mental health system. The authors conclude that outpatient commitment programs are vulnerable to legal challenge because they may depart from established constitutional standards for involuntary treatment.
What makes a goal or a precondition a better explanation of an action or outcome? Recent research shows that whereas goals are preferred for common actions, preconditions are preferred for actions that require substantial resources, particularly when those actions are obstructed. Two studies examined whether judgments of goals and preconditions reflect the controllability of the events, and whether previous findings apply to events generated by participants. Participants judged goals and preconditions as explanations for desirable extreme and moderate events and assessed the controllability and probability of the events. For common events, goals were better explanations than preconditions, whereas for the extreme scenarios, preconditions were judged equal or better explanations. The extreme events were seen as less controllable than the moderate events, and the controllability of the events predicted judgments of goals as explanations. The results suggest that participants see goals as better explanations only for events that the person can control, and they judge preconditions to be good explanations for events where the person has little control. These findings suggest that equifinality may apply only to those actions and outcomes where the preconditions are readily obtainable.
BACKGROUND AND OBJECTIVES: Most patients with familial hemophagocytic lymphohistiocytosis (HLH) develop the disease within the first two years of age. In a minority of cases a later occurrence has been reported, with an upper age limit of eight years. A significant concordance of the age at onset within each family has also been observed. RESULTS: We report four cases of families with HLH diagnosed at an unusually late age, comprised between between 9 and 17 years; in each of these families another child developed the disease in infancy. The natural killer activity of the patients was depleted; nevertheless, we had indirect evidence that, in at least two families, mutations of the perforin gene were not causing the disease. INTERPRETATION AND CONCLUSIONS: Such a late onset is very unusual and suggests that there is a subgroup of families with HLH in which the disease may present early or late in different members. Thus in some families with HLH the siblings might remain at risk of developing the disease for several years. Their actual risk cannot be defined until the genetic mutation is identified in each family and assessed in each member.
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The further optimisation of the novel lead compound CGH752 (Fig. 1) is described. By introducing various substituents into the 6-position of the 3,3-dimethyltetrahydroquinoline (DMTHQS) ring we have been able to favourably affect the in vitro and in vivo activity, and the pharmacokinetics of such compounds. One of the inhibitors synthesised (CGH1484) is bioavailable and shows efficacy in animal models of thrombosis.
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