Effect of chronic L-DOPA administration on catecholamine metabolism in the rat

1. L-DOPA was administered to rats by twice daily intraperitoneal injection for a period of eleven days. The daily dose was gradually increased from 250 mg/kg to 1 g/kg. The animals were killed 12 h after the last injection and tissue catechol-O-methyl transferase, DOPA-decarboxylase and monoamine oxidase activity determined.2. Catechol-O-methyl transferase activity was reduced in the liver (46%) and red blood cells (38%) but was approximately doubled in the heart.3. Liver DOPA-decarboxylase activity was reduced by approximately 25%.4. L-DOPA administration did not significantly affect the activity of any of the enzymes studied in brain tissue.     

Sequential molecular and cellular events during neoplastic progression: a mouse syngeneic ovarian cancer model

Studies performed to identify early events of ovarian cancer and to establish molecular markers to support of early detection and the development of chemopreventive regimens have been hindered by a lack of adequate cell models. Taking advantage of the spontaneous transformation of mouse ovarian surface epithelial (MOSE) cells in culture, we isolated and characterized distinct transitional stages of ovarian cancer as the cells progressed from a premalignant nontumorigenic phenotype to a highly aggressive malignant phenotype. Transitional stages were concurrent with progressive increases in proliferation, anchorage-independent growth capacity, in vivo tumor formation, and aneuploidy. During neoplastic progression, our ovarian cancer model underwent distinct remodeling of the actin cytoskeleton and focal adhesion complexes, concomitant with downregulation and/or aberrant subcellular localization of two tumor-suppressor proteins E-cadherin and connexin-43. In addition, we demonstrate that epigenetic silencing of E-cadherin through promoter methylation is associated with neoplastic progression of our ovarian cancer model. These results establish critical interactions between cellular cytoskeletal remodeling and epigenetic silencing events in the progression of ovarian cancer. Thus, our MOSE model provides an excellent tool to identify both cellular and molecular changes in the early and late stages of ovarian cancer, to evaluate their regulation, and to determine their significance in an immunocompetent in vivo environment.     

Another use for the seven-pinhole collimator. Routine nontomographic imaging of the thyroid

Relatively few seven-pinhole collimator systems purchased within the last three years are still in routine use. This paper describes a nontomographic use of the collimator for thyroid scanning. One image is obtained which simultaneously shows seven different projections of the thyroid gland. The diagnosis of thyroid abnormalities can frequently be made from this single composite image without the requirement for additional images. Further information can be obtained when needed by computer processing the image into tomographic slices.     

Acquired pendular nystagmus: its characteristics, localising value and pathophysiology

Investigations were made of 16 patients with acquired pendular nystagmus and a further 32 cases reported in the literature were reviewed. Amongst our own patients two thirds had multiple sclerosis, almost one third a cerebrovascular accident or angioma and two had optic atrophy with squint. The nystagmus took forms which could be monocular or binocular, conjugate or disconjugate and could involve movements about single or multiple axes. Spectral analysis was used to characterise the amplitude and frequency of the movements and to estimate the degree of relationship (coherence) between movements of the two eyes or between movements of one eye about several axes. The oscillations ranged in frequency from 2·5 Hz to 6 Hz, with typical amplitudes between 3° and 5°. In a given patient all oscillations, regardless of plane, were highly synchronised. Somatic tremors of the upper limb, face and palate associated with the nystagmus were often at similar frequencies to the eye movement. The other ocular signs common to all our patients were the presence of squint with failure of convergence. Most patients also had skew deviation or internuclear ophthalmoplegia or both. The major oculomotor systems, that is, saccades, pursuit, optokinetic and vestibulo-ocular reflexes could be intact. It is inferred that the mechanism responsible for the pendular nystagmus lies at a level which is close to the oculomotor nuclei so that it can have monocular effects but is not part of the primary motor pathways. It is possible that this mechanism normally subserves maintenance of conjugate movement and posture of the eyes. The periodicity of the nystagmus is likely to arise from instability in a certain type(s) of neurone, for the associated somatic tremors have similar characteristics and yet involve very different neuronal muscular circuitry. Prognosis for cessation of the nystagmus is poor. In five patients with multiple sclerosis it was suppressed by intravenous hyoscine with, however, unacceptable subsequent side effects.     

Ulcer formation and cytoprotection by acetazolamide

Acetazolamide, a carbonic anhydrase inhibitor, was administered orally and subcutaneously to rats. Acetazolamide increased the gastric ulcerogenicity of indomethacin, but inhibited gastric ulcers produced by acidified aspirin. When administered alone to fasted rats, it did not produce gastric ulcers. Acetazolamide was also cytoprotective for the stomach (it reduced dose dependently the number of gastric necrotic lesions caused by absolute ethanol given orally) and for the small intestine (it prevented dose dependently intestinal lesions produced by administration of a high dose of indomethacin). Acetazolamide did not prevent the antiulcer effect of PGE2 (against aspirin-induced ulcers) nor the cytoprotective effect of 16,16-dimethyl PGE2 (against ethanol-induced gastric lesions). The degree of gastric cytoprotection increased with time after a single administration of acetazolamide; the optimal effect occurred 60 and 90 min after oral and subcutaneous administration, respectively. Pretreatment with indomethacin completely prevented the cytoprotective effect of acetazolamide; this suggests that the cytoprotective effect may be mediated by endogenous release of prostaglandins by the stomach. All the effects of acetazolamide reported here were observed after either oral or subcutaneous administration. The mechanism by which acetazolamide influences ulcer formation and is cytoprotective is unknown.     

Effect of errors in reangulation on planar and tomographic thallium-201 washout profile curves

Cardiac phantom studies were performed with and without a defect present to test the hypothesis that myocardial 201TI quantitative circumferential washout profile curves calculated from planar and rotating slant hole (RSH) collimator tomographic images are equally affected by errors in axial repositioning. Simulated stress images were acquired with the long axis of the phantom perpendicular to the camera surface and redistribution images were acquired to represent 50% 201TI washout with axial repositioning errors relative to the stress position ranging from 0 to 20 degrees in 5 degrees increments. There was a decrease in the 201TI washout profile curves compared to that expected (50%) in the wall tilted away from the camera surface, and a reciprocal increase in the 201TI washout profile curves in the wall tilted towards the camera surface for both imaging techniques whether a lesion was present or not. This effect became more pronounced as the error in axial repositioning was increased for both the planar (p less than 0.001) and the RSH tomographic (p less than 0.001) techniques. However, the deviation of the 201TI washout profile curves from that expected (50%) was greater for the planar imaging technique with or without a lesion (p less than 0.05 to 0.001). Thus, we conclude that 201TI quantitative circumferential washout profile curves calculated using this tomographic imaging technique are less affected by errors in axial repositioning than those calculated using an equivalent projection by standard planar imaging methods. These data emphasize the importance which must be placed on the repositioning of patients to obtain valid 201TI washout profile curves for the detection and localization of coronary artery disease.