Studies on a second and third ring cyclization in anthracycline biosynthesis

This paper focuses on study of second and third ring cyclization in anthracycline biosynthesis by a heterologous gene expression. Firstly, anthracycline non-producing Streptomyces peucetius mutant, D2 was heterologously complemented to produce daunomycins with plasmids pSgs44 and pSYE66, which contain putative cyclase genes of S. galilaeus and S. nogalater, respectively. A point mutation in the cyclase gene dpsY of D2 has changed glycine to serine resulting inactivation of the enzyme. Secondly, the putative cyclase gene snoaM from S. nogalater, was expressed in a gene cassette in S. lividans TK24 and S. coelicolor CH999 to study the influence of the cyclase gene on auramycinone production and the impact of endogenous genes on production profiles. The results obtained confirms that a cyclase closing the second and third ring of a polyketide is essential in anthracycline biosynthesis.     

Altered levels of cerebrospinal fluid reelin in frontotemporal dementia and Alzheimer's disease

Reelin is an essential glycoprotein for correct cytoarchitectonic organization during CNS development. Its function in the adult brain is far less well understood, but altered brain and blood reelin levels have been reported in some psychiatric disorders, and the possibility has been considered of an involvement of the reelin signaling pathway in neurodegeneration. Here we report, for the first time, the presence of detectable levels of reelin in rat and human cerebrospinal fluid (CSF) and show evidence for the involvement of a 180-kDa reelin fragment in two neurodegenerative disorders. This fragment was analyzed by Western blotting in CSF samples from 13 healthy control individuals and 14 frontotemporal dementia (FTD) and 20 Alzheimer's disease (AD) patients. Increased CSF 180-kDa reelin was found in FTD (161.7 +/- 6.7 arbitrary units; a.u.) and AD (151.4 +/- 3.8 a.u.) compared with control individuals (141.4 +/- 1.2 a.u., P < 0.05). Our results strongly suggest the involvement of reelin signaling in neurodegenerative pathologies.     

CSF markers for pathogenic processes in Alzheimer's disease: diagnostic implications and use in clinical neurochemistry

In view of current (acetylcholine esterase (AChE) inhibitors) and future (e.g. gamma-secretase inhibitors) therapeutic compounds for treatment of Alzheimer's disease (AD), the development and evaluation of cerebrospinal fluid (CSF) biomarkers for AD has become a rapidly growing research field. Diagnostic biomarkers for AD would be especially valuable as aids to diagnosis early in the course of the disease, when correct diagnosis is difficult, and when therapeutic compounds have the greatest potential for being effective. This paper reviews CSF biomarkers for AD, with emphasis on their role in the clinical diagnosis. The two most studied biochemical markers, CSF-tau and CSF-Abeta42, have high sensitivity to identify AD, but the specificity against other dementias is lower. The addition of phosphorylated tau (P-Tau) seems to increase the specificity for the diagnosis of AD, since normal levels are found in both frontotemporal and Lewy body dementia, and in cerebrovascular disease. These CSF markers may be useful as diagnostic aids, especially to discriminate early or incipient AD from age-associated memory impairment, depression, and some secondary dementias.     

Verrucous squamous cell carcinoma of the female genital tract. Report of three cases and survey of the literature

Three new cases of gynecological verrucous squamous cell carcinomas are reported; one in the uterine cervix, and two in the vulva. The English literature covering the 49 cases reported previously is surveyed with special reference to the diagnostic and therapeutic aspects of these tumors, as well as with their clinical behavior and possible relationship to viral (HPV) lesions (Condylomas) of the genital tract.It was concluded that so far the exact relationship between the different verrucous squamous cell lesions in the genital tract remains obscure, all such lesions should be regarded as potentially malignant, and treated accordingly by radical surgery.     

Patient satisfaction after knee arthroplasty: A report on 27,372 knees operated on between 1981 and 1995 in Sweden

During a validation process of the Swedish Knee Arthroplasty Register (SKAR), living registered patients were sent a questionnaire to ask if they had been reoperated on. This gave an opportunity to pose a simple four-point question with respect to patient satisfaction which 95% of patients answered. We analyzed the answers of patients operated on between 1981 and 1995 and found that only 8% of the patients were dissatisfied regarding their knee arthroplasty 2-17 years postoperatively. The satisfaction rate was constant, regardless of when the operation had been performed during the 15-year period. The proportion of satisfied patients was affected by the preoperative diagnosis, patients operated on for a long-standing disease more often being satisfied than those with a short disease-duration. There was no difference in proportions of satisfied patients, whether they had primarily been operated on with a total knee arthroplasty (TKA) or a medial unicompartmental arthroplasty (UKA). For TKAs performed with primary patellar resurfacing, there was a higher ratio of satisfied patients than for TKAs not resurfaced, but this increased ratio diminished with time passed since the primary operation. Unrevised knees had a higher proportion of satisfied patients than knees that had been subject to revision, and among patients revised for medial UKA, the proportion of satisfied patients was higher than among patients revised for TKA. We conclude that satisfaction after knee arthroplasty is stable and long-lasting in unrevised cases and that even after revision most patients are satisfied.     

A Prospective Study of Neck,Shoulder, and Upper Back Pain Among Technical School Students Entering Working Life

PurposeThe aim of this prospective study was to relate the prevalence of neck, shoulder, and upper back pain to occupational and individual risk factors among a population of technical school students in their transition from school to working life. In addition, we wanted to assess the changes in pain prevalence during follow-up.MethodsA cohort consisting of 173 technical school students was followed up during a 3-year period, from their last year of school through their first years of working life. Data on self-reported neck, shoulder, and upper back pain and factors such as mechanical exposure, perceived stress, and physical activity in leisure time were collected.ResultsA high prevalence of pain in the neck, shoulder, and upper back among the technical school students was found. There were however few students reporting severe pain. Reporting pain at baseline gave over three times higher risk of reporting it at follow-up. A high level of physical activity outside working hours gave a lower risk of reporting neck, shoulder, and upper back pain at follow-up. High and moderate levels of mechanical exposure and high stress level were not found to be risk factors for pain after entering working life.ConclusionNeck, shoulder, and upper back pain are common among adolescents and may persist into working life. These results may give potential for preventive efforts at a young age. There is still much uncertainty about the factors leading to musculoskeletal pain, and more research is needed on this topic.