A “Stopper” mutant of Neurospora crassa containing two populations of aberrant mitochondrial DNA

Summary [E35], an extranuclear mutant of Neurospora crassa has all the phenotypic characteristics of the stopper mutants (De Vries et al. 1980). In the present work, the mitochondrial DNA as well as the mitochondrial translation products are characterized further. The primary mutational event appears to have been the deletion of about 4 kbp from the wild-type genome. Moreover, after prolonged vegetative growth the mutant accumulates an 8-m circular mtDNA, which was demonstrated both by electronmicroscopy and by restriction enzyme analysis. Hence, the mutant contains two populations of aberrant mitochondrial DNA, the smaller of which is an amplification of the rRNA-tRNA part of the larger. We propose that the primary deletion has generated a signal in the larger DNA which can cause premature termination of replication at the deletion site, and subsequent circularization of the unfinished daughter molecule. Finally, the deleted part may contain a determinant for synthesis of a protein of 11 kDal. The function of this protein, which is not a subunit of the F₀ ATPase, is not yet known.Abbreviations (k)bp (kilo)basepairs - kDal kilodalton - mt mitochondrial     

Neck muscle responses to stimulation of monkey superior colliculus. II. Gaze shift initiation and volitional head movements

We report neck muscle activity and head movements evoked by electrical stimulation of the superior colliculus (SC) in head-unrestrained monkeys. Recording neck electromyography (EMG) circumvents complications arising from the head's inertia and the kinetics of muscle force generation and allows precise assessment of the neuromuscular drive to the head plant. This study served two main purposes. First, we sought to test the predictions made in the companion paper of a parallel drive from the SC onto neck muscles. Low-current, long-duration stimulation evoked both neck EMG responses and head movements either without or prior to gaze shifts, testifying to a SC drive to neck muscles that is independent of gaze-shift initiation. However, gaze-shift initiation was linked to a transient additional EMG response and head acceleration, confirming the presence of a SC drive to neck muscles that is dependent on gaze-shift initiation. We forward a conceptual neural architecture and suggest that this parallel drive provides the oculomotor system with the flexibility to orient the eyes and head independently or together, depending on the behavioral context. Second, we compared the EMG responses evoked by SC stimulation to those that accompanied volitional head movements. We found characteristic features in the underlying pattern of evoked neck EMG that were not observed during volitional head movements in spite of the seemingly natural kinematics of evoked head movements. These features included reciprocal patterning of EMG activity on the agonist and antagonist muscles during stimulation, a poststimulation increase in the activity of antagonist muscles, and synchronously evoked responses on agonist and antagonist muscles regardless of initial horizontal head position. These results demonstrate that the electrically evoked SC drive to the head cannot be considered as a neural replicate of the SC drive during volitional head movements and place important new constraints on the interpretation of electrically evoked head movements.     

Quantitation of the visual field

With kinetic perimetry, the visual field chart had the appearance of a geographical map. Since the isopters were not geometric, their surfaces were barely measurable. However, with recent three dimensional computerised (or semi-computerised) perimetry quantitative evaluation of the print-out may easily be done. The visual acuity is expressed by a fraction or ratio. In a similar way our deficit ratio gives a percentage score of visual field volume defects. Using the Peritest, it is very easy to establish the field's deficit ratio. All the defects are classified and have a score. Scores are then added up to establish the deficit ratio. (The same procedure may be used with other perimeters like the Visual Field Analyser). Why express field loss as a deficit ratio? In the natural history of a Primary Open Angle Glaucoma (i.e. a disease of the visual field), the comparison between consecutive visual fields may be difficult. Instead of looking at a collection of print outs, it is easier to look at the numbers of the deficit ratio to appreciate if there is evolution of the disease. In discussions with the patient, it sounds better if the ophthalmologist speaks of a "percentage" of visual field loss: the patient may understand his own situation more easily. Each point is tested twice at each examination to give an idea of patient response fluctuation. Before finding progression of the disease, it is necessary to know the range of an individual's variation in answers. The principle of all sciences is to measure what is measurable, and to render measurable that which is not.     

Relationship between Cigarette Dose and Perceived Risk of Lung Cancer

BACKGROUND: Most people are aware that smoking cigarettes increases the risk of ill health, in particular of lung cancer. The precise way in which they relate amount of exposure to smoke and level of health risk has not, however, been determined. METHODS: A convenience sample of 155 French adolescents and adults ages 15 to 75 rated the risk of "smoker's cancer"--the popular term for lung cancer--in 24 scenarios depicting eight levels of daily cigarette consumption of three concentrations of nicotine. The data were analyzed according to functional measurement methodology to ascertain the forms of the relationship between exposure and perceived risk. RESULTS: All subjects perceived that the risk of smoker's cancer increased as smoking increased. Yet at high levels of consumption, additional cigarettes were generally judged to result in decreasing increments of risk, regardless of the nicotine content of the cigarettes and the sex and smoking status of the participants. Adolescents, however, were more likely than adults to perceive a linear, rather than a negatively accelerated, relationship. CONCLUSIONS: The actual form of the relationship between the dose of cigarette smoke and risk of lung cancer is either linear or positively accelerated. Public health educators and physicians should be aware that, at least in France, many people, particularly adults, incorrectly perceive this relationship as negatively accelerated.     

Iatrogenic Thyrotoxicosis: Causal Circumstances, Pathophysiology, and Principles of Treatment—Review of the Literature

Thyrotoxicosis is the clinical syndrome that results when tissues are exposed to high levels of circulating thyroid hormones. In most instances thyrotoxicosis is due to hyperthyroidism, a term reserved for disorders characterized by overproduction of thyroid hormones by the thyroid gland. Nevertheless, thyrotoxicosis may also result from a variety of conditions other than thyroid hyperfunction. The present report focuses on the etiologies, pathophysiology, and treatment of iatrogenic thyrotoxicosis. Iatrogenic thyrotoxicosis may be caused by (1) subacute thyroiditis (a result of lymphocytic infiltration, cellular injury, trauma, irradiation) with release of preformed hormones into circulation; (2) excessive ingestion of thyroid hormones (“thyrotoxicosis factitia”); (3) iodine-induced hyperthyroidism (radiologic contrast agents, topical antiseptics, other medications). Among these causes of iatrogenic thyrotoxicosis, that induced by the iodine overload and cytotoxicity associated with amiodarone represents a significant challenge. Successful management of amiodarone-induced thyrotoxicosis requires close cooperation between endocrinologists and endocrine surgeons. Surgical treatment may have a leading yet often underestimated role in view of the potential life-threatening severity of this disease, whereas others kinds of iatrogenic thyrotoxicosis are usually treated conservatively.     

How to optimize physicians' communication skills in cancer care: results of a randomized study assessing the usefulness of posttraining consolidation workshops.

PURPOSE: Although there is wide recognition of the usefulness of improving physicians' communication skills, no studies have yet assessed the efficacy of post-training consolidation workshops. This study aims to assess the efficacy of six 3-hour consolidation workshops conducted after a 2.5-day basic training program. METHODS: Physicians, after attending the basic training program, were randomly assigned to consolidation workshops or to a waiting list. Training efficacy was assessed through simulated and actual patient interviews that were audiotaped at baseline and after consolidation workshops for the consolidation-workshop group, and approximately 5 months after the end of basic training for the waiting-list group. Communication skills were assessed according to the Cancer Research Campaign Workshop Evaluation Manual. Patients' perceptions of communication skills improvement were assessed using a 14-item questionnaire. RESULTS: Sixty-three physicians completed the training program. Communication skills improved significantly more in the consolidation-workshop group compared with the waiting-list group. In simulated interviews, group-by-time repeated measures analysis of variance showed a significant increase in open and open directive questions (P =.014) and utterances alerting patients to reality (P =.049), as well as a significant decrease in premature reassurance (P =.042). In actual patient interviews, results revealed a significant increase in acknowledgements (P =.022) and empathic statements (P =.009), in educated guesses (P =.041), and in negotiations (P =.008). Patients interacting with physicians who benefited from consolidation workshops reported higher scores concerning their physicians' understanding of their disease (P =.004). CONCLUSION: Consolidation workshops further improve a communication skills training program's efficacy and facilitate the transfer of acquired skills to clinical practice.     

Left ventricular stimulation in treatment of heart failure

SEARCH FOR AN ALTERNATIVE TREATMENT: The concept of stimulating the ventricle to improve heart function in patients with severe heart failure is an old one, but the first published series was reported about 10 years ago and provided encouraging results that lead to numerous other studies. A PROMISING TECHNIQUE: Excepting a few patients with a long PR, stimulation of the right ventricle is ineffective or even deleterious. Stimulation of the lateral region of the left ventricle has produced some undeniably favorable and sometimes even spectacular improvement in hemodynamic performances. Permanent stimulation of both ventricles or the left ventricle produces an overall clinical improvement in patients with severe heart failure (NYHA III or IV) and major left intraventricular conduction disorders (QRS > 140 ms). These results have been recently confirmed in a prospective randomized trial. CAREFUL OPEN QUESTIONS: There is no fully satisfactory explanation for the improvement which, it is important to note, does not occur in all patients. A more homogeneous contraction of the left ventricle certainly plays a fundamental role. Resynchronization of the two ventricles with dual stimulation is more complex and costly and remains to be evaluated. One crucial question is currently being examined: what is the effect of stimulation on the high mortality in these patients?