Fusarium graminearum A 3/5 as a novel host for heterologous protein production

We describe a novel fungal expression system which utilizes the Quorn myco-protein fungus Fusarium graminearum A 3/5. A transformation system was developed for F. graminearum and was used to introduce the coding and regulatory regions of a trypsin gene from Fusarium oxysporum. The protein was efficiently expressed, processed and secreted by the recombinant host strain. In addition, the promoter and terminator of the F. oxysporum trypsin gene have been successfully utilized to drive the expression of a cellulase gene from Scytalidium thermophilum and a lipase gene from Thermomyces lanuginosus in F. graminearum.     

Occupational exposures and amyotrophic lateral sclerosis. A population-based case-control study

This population-based case-control study was conducted in three countries in western Washington State to evaluate associations between workplace exposures and the risk of amyotrophic lateral sclerosis (ALS). Cases (n = 174) were all newly diagnosed with ALS by neurologists during 1990-1994, and controls (n = 348), who were matched according to age (+/-5 years) and sex, were identified via random-digit dialing or Medicare enrollment files. Four industrial hygienists blindly assessed detailed lifetime job histories for exposures to metals, solvents, and agricultural chemicals. Case-control comparisons were made for jobs held between 15 years of age and 10 years prior to the cases' dates of diagnosis. After adjustment for age and education, ever exposure to agricultural chemicals was associated with ALS (odds ratio (OR) = 2.0, 95% confidence interval (CI) 1.1-3.5); this association was observed separately in men (OR = 2.4, 95% CI 1.2-4.8) but not in women (OR = 0.9, 95% CI 0.2-3.8). Among men, the odds ratio for low exposure to agricultural chemicals (below the median level for exposed controls) relative to no exposure was 1.5 (95% CI 0.4-5.3), and for high exposure, it was 2.8 (95% CI 1.3-6.1) (p for trend = 0.03). Similar analyses based on the panel's assessment of exposures to metals and solvents showed no associations. These findings suggest an association between ALS and agricultural chemicals in men.     

Stroke and use of low-dose oral contraceptives in young women: a pooled analysis of two US studies

BACKGROUND AND PURPOSE: The available data on low-dose oral contraceptive pill (OCP) use and stroke risk in US women are limited by small numbers. We sought more precise estimates by conducting a pooled analysis of data from 2 US population-based case-control studies. METHODS: We analyzed interview data from 175 ischemic stroke cases, 198 hemorrhagic stroke cases, and 1191 control subjects 18 to 44 years of age. RESULTS: For ischemic stroke, the pooled odds ratio (pOR) adjusted for stroke risk factors for current use of low-dose OCPs compared with women who had never used OCP (never users) was 0.66 (95% confidence interval [CI], 0.29 to 1.47) and compared with women not currently using OCPs (nonusers) the pOR was 1.09 (95% CI, 0.54 to 2.21). For hemorrhagic stroke, the pOR for current use of low-dose OCPs compared with never users was 0.95 (95% CI, 0.46 to 1.93) and compared with nonusers the pOR was 1.11 (95% CI, 0.61 to 2.01). The pORs for current low-dose OCP use and either stroke type were not elevated among women who were >/=35 years, cigarette smokers, obese, or not receiving medical therapy for hypertension. pORs for current low-dose OCP use were 2.08 (95% CI, 1. 19 to 3.65) for ischemic stroke and 2.15 (95% CI, 0.85 to 5.45) for hemorrhagic stroke among women reporting a history of migraine but were not elevated among women without such a history. Past OCP use (irrespective of formulation) was inversely related to ischemic stroke but unrelated to hemorrhagic stroke. CONCLUSIONS: Women who use low-dose OCPs are, in the aggregate, not at increased risk of stroke. Studies are needed to clarify the risk of stroke among users who may be susceptible on the basis of age, smoking, obesity, hypertension, or migraine history.     

Toynbee Memorial Lecture 1997. Middle ear mechanics in normal, diseased and reconstructed ears

A review of the structure-function relationships in normal, diseased and reconstructed middle ears is presented. Variables used to describe the system are sound pressure, volume velocity and acoustic impedance. We discuss the following: (1) Sound can be transmitted from the ear canal to the cochlea via two mechanisms: the tympanoossicular system (ossicular coupling) and direct acoustic stimulation of the oval and round windows (acoustic coupling). In the normal ear, middle-ear pressure gain, which is the result of ossicular coupling, is frequency-dependent and smaller than generally believed. Acoustic coupling is negligibly small in normal ears, but can play a significant role in some diseased and reconstructed ears. (2) The severity of conductive hearing loss due to middle-ear disease or after tympanoplasty surgery can be predicted by the degree to which ossicular coupling, acoustic coupling, and stapes-cochlear input impedance are compromised. Such analyses are used to explain the air-bone gaps associated with lesions such as ossicular interruption, ossicular fixation and tympanic membrane perforation. (3) With type IV and V tympanoplasty, hearing is determined solely by acoustic coupling. A quantitative analysis of structure-function relationships can both explain the wide range of observed post-operative hearing results and suggest surgical guidelines in order to optimize the post-operative results. (4) In tympanoplasty types I, II and III, the hearing result depends on the efficacy of the reconstructed tympanic membrane, the efficacy of the reconstructed ossicular chain and adequacy of middle-ear aeration. Currently, our knowledge of the mechanics of these three factors is incomplete. The mechanics of mastoidectomy and stapedectomy are also discussed.     

Discrimination between myocardial and skeletal muscle injury by assessment of the plasma ratio of myoglobin over fatty acid-binding protein

BACKGROUND: Myoglobin and fatty acid-binding protein (FABP) each are useful as early biochemical markers of muscle injury. We studied whether the ratio of myoglobin over FABP in plasma can be used to distinguish myocardial from skeletal muscle injury. METHODS AND RESULTS: Myoglobin and FABP were assayed immunochemically in tissue samples of human heart and skeletal muscle and in serial plasma samples from 22 patients with acute myocardial infarction (AMI), from 9 patients undergoing aortic surgery (causing injury of skeletal muscles), and from 10 patients undergoing cardiac surgery. In human heart tissue, the myoglobin/FABP ratio was 4.5 and in skeletal muscles varied from 21 to 73. After AMI, the plasma concentrations of both proteins were elevated between approximately 1 and 15 to 20 hours after the onset of symptoms. In this period, the myoglobin/FABP ratio was constant both in subgroups of patients receiving and those not receiving thrombolytics and amounted to 5.3 +/- 1.2 (SD). In serum from aortic surgery patients, both proteins were elevated between 6 and 24 hours after surgery; the myoglobin/FABP ratio was 45 +/- 22 (SD), which is significantly different from plasma values in AMI patients (P < .001). In patients with cardiac surgery, the ratio increased from 11.3 +/- 4.7 to 32.1 +/- 13.6 (SD) during 24 hours after surgery, indicating more rapid release of protein from injured myocardium than from skeletal muscles. CONCLUSIONS: The ratio of the concentrations of myoglobin over FABP in plasma from patients with muscle injury reflects the ratio found in the affected tissue. Since this ratio is different between heart (4.5) and skeletal muscle (20 to 70), its assessment in plasma allows the discrimination between myocardial and skeletal muscle injury in humans.     

Effect of cAMP-induced transcription on the repair of the phosphoenolpyruvate carboxykinase gene by hepatocytes isolated from young and old rats

Animal experiments suggest that the fetal brain is sensitive to nicotine. Although much attention has been given to the relation between cigarette smoking during pregnancy and neurodevelopment in children, this remains controversial. Our study describes the relationship between maternal cigarette smoking during pregnancy and babbling abilities of the 8-month-old infant. In a longitudinal cohort, information was collected at the 16th week of gestation, at delivery and when the infant was about 8 months old. At this age babbling abilities of the infant were evaluated by a health visitor during a home visit. Singleton infants without any disability born at Aarhus University Hospital, Denmark, 1991-92 and still living in the Community of Aarhus at the age of 8 months were eligible (n = 2302). Complete follow-up was obtained for 1871 children (81.3%). A dose-response-like relationship between number of cigarettes smoked per day during pregnancy and babbling abilities was found after controlling for potential confounders. Smoking 10 or more cigarettes per day during pregnancy almost doubled the risk (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.1-3.6) of the infant being a non-babbler at the examination at 8 months. Among children who were breast fed for less than 4 months this risk was even higher (OR = 2.7, CI 1.3-5.8).     

Functional neuroanatomy of the basal ganglia as studied by dual-probe microdialysis

This is a report of two cases of mature mediastinal teratoma associated with elevated serum SCC levels. The first patient was a 17-year-old female admitted to our hospital for severe left chest pain. Chest x-ray film and CT scan showed a mediastinal tumor. The preoperative serum SCC level was elevated. Resection was performed and the pathological diagnosis was mature teratoma. The second patient was a 32-year-old male admitted to our hospital for severe anterior chest pain. A chest CT scan showed a mediastinal tumor. The preoperative serum SCC level was high. Surgery was performed and the pathological diagnosis was mature teratoma. The cause of the high serum SCC levels was unclear, but we suspect that the pulmonary atelectasis may have caused it.     

Assessment of factors affecting palpability of breast masses using ultrasonography in Chinese women

Five hundred and twenty-nine women with self-discovered or clinically palpable breast lumps had physical examination followed by high-resolution ultrasonographic examination of the breast. A total of 482 palpable and 146 nonpalpable masses were discovered by ultrasonography. The median values of the breast stromal, premammary, and retromammary fat thickness measurements were 1.3 cm, 0.1 cm, and 0.1 cm, respectively. The median depths of the lesions and the distance of the lesions from the pectoralis muscle were 0.5 cm and 0.2 cm, respectively. The median size of all breast masses was 1.5 cm. These measurements (of the tissue characteristics of the breast, location of the breast mass, and size of the breast lesion) were correlated with palpability or nonpalpability of the breast lesions. Multivariate logistic regression performed for all breast masses showed the only significant factors affecting palpability to be the size (anteroposterior and transverse diameters) and the depth of a breast mass. This is expressed by the following equation: [formula: see text] where z = -0.8759 + 0.9691 (g) + 2.2770 (e)-1.5332 (d), and d represents depth of lesion from the cutaneous surface and e and g represent anteroposterior and transverse diameters of the breast mass, respectively. The nature of the breast tissue (i.e., the premammary fat, retromammary fat, or breast stromal thickness as determined by ultrasonography) does not affect palpability. This study would therefore strongly support the recommendation of breast self-examination, irrespective of breast structure.