Inducers of the cytochrome P-450 superfamily as promoters of carcinogenesis

This review summarizes data on the mechanisms of tumor-promoting activity of non-genotoxic compounds that are inducers of cytochrome P-450 isoforms. Their promoting activity is analyzed in term of synthesis of new cytochrome P-450 isoforms. Active oxygen species formed by cytochrome P-450 isoforms can simultaneously act as stimulators of proliferation and inhibitors of intercellular communications. Promoter effects can be associated with changes in the ratio of cellular signaling non-protein molecules induced by newly synthesized cytochrome P-450 isoforms. Data on induction of cytochrome P-450 isoforms of family 1 indicate that inducer interaction with its receptor causes cellular events resulting in the stimulation of cell proliferation.     

Photosensitive epilepsy

Photosensitive epilepsy (PE) is the most frequent form of reflex epilepsy. Authors picked out two PE forms based on the analysis of the 16 own observations. The first form is PE with environmental factors of the process' provocation, which is characterised by genuine character of disease, pre- and pubertal period of its beginning, considerable prevalence of males among the patients, rare generalized tonic and clonic fits and favorable prognosis. The second form of PE is significantly rarer PE form -with self-induction of the fits. It is characterized by the beginning of the disease in preschool period, even sex distribution, quite frequent evaluated organic damages of brain, nonconvulsive fits, non-efficiency of antiepileptic drugs. The mechanisms of pathogenesis and the ways of fits' prophylaxis were discussed.     

Recent advances in the treatment of type II diabetes mellitus

Diabetes mellitus needs to be managed early to prevent the onset and progression of complications. Diet and exercise may not be sufficient to achieve and maintain good glycemic control. Currently, no pharmacologic agent addresses all of the fundamental abnormalities in the pathogenesis of type II diabetes mellitus. However, the newer agents do not exacerbate the hyperinsulinemia that often occurs with type II diabetes, and they may help reduce the risk of cardiovascular disease that is associated with high insulin levels. Two of these agents, metformin and acarbose, have recently become available in the United States for the treatment of type II diabetes. With the availability of agents that differ in their mechanisms of action and side effect profiles, regimens can be individualized to address the variety of pathophysiologic abnormalities in type II diabetes. For this purpose, agents can be used alone or in combination.     

Novel derivatives of cyclodextrins, modified with poly(ethylene oxide) and their complexation properties

Sodium chloride transport across isolated cecum mucosa was investigated in normal rats and rats with adaptive cecum growth induced by dietary polyethylene glycol (PEG). The normal cecum absorbed Cl in excess of Na with a small short-circuit current (ISC). Dietary adaptation led to large equivalent increments of Na and Cl net absorption without adequate ISC change. Inhibitor studies (mucosal amiloride 10(-3) and 10(-4) M; mucosal 4, 4-diisothiocyanatostilbene-2,2-disulfonic acid 5 x 10(-5) M; serosal furosemide 10(-3) M; serosal ouabain 10(-3) M) suggested that normal cecal NaCl absorption involves electroneutral Na/H and Cl/HCO3 exchange at the apical and Na-K-ATPase-mediated exit across the basolateral cell membrane. Dietary adaptation stimulates the loosely coupled antiports and possibly activates a small serosally located NaCl cotransport. Comparative histology showed flattening of all tissue layers and widening of crypts in PEG animals. Crypt widening may facilitate ion access to underutilized transport sites and, at least in part, explain the increased absorption of the enlarged cecum.     

Expanded phase II trial of paclitaxel in metastatic breast cancer: a Southwest Oncology Group study

In digital image processing, the homomorphic filtering approach is derived from an illumination-reflectance model of the image. Homomorphic filtering can perform simultaneous dynamic range compression and contrast enhancement. Crucial for the success of the homomorphic approach is the selection of an appropriate frequency-domain filter function in order to modify the illumination and reflectance components of an image differently. The author found Butterworth type highpass equations far superior to other frequency-domain filter functions, including Gaussian equations, making the Butterworth highpass suitable for use with the homomorphic filtering approach. The program was written in Microsoft (MS) Visual C++ (filter) as well as MS Visual Basic (user interface) to run as a module under the image processing software package Image-Pro Plus.     

Tuberculosis in psychoneurological boarding houses of Sverdlovsk region

Since 1993, the pace of increased tuberculosis mortality and morbidity rates in patients with mental disorders has essentially out-stripped that for the general population in the Sverdlovsk Region. At the same time, the highest tuberculosis mortality and morbidity rates were seen in contingents of psychoneurological boarding houses (PBH) where not only sporadic (single), but group cases of tuberculosis, as well as its outbreaks (epidemics), including massive ones has been annually notified in recent years. In 1993-1996, the mean morbidity rate among those present in PBH was 10.5 times as high as that among the general adult population in the region.     

Differential diagnosis of pleural effusion

The results of following up 598 patients diagnosed as having pleural exudate were used to analyze the potentialities of complex radiation and clinical differential diagnoses of this abnormality. The authors identified 4 most common nosological entities (tuberculosis, pleuropneumonia, cancer, mesothelioma) among patients of diagnostic hospitals. The diagnostic algorithm should be derived by taking into account the current techniques applicable to each disease form. With this, valid diagnosis may be made in 98.5% of cases.     

Disruption of polytenization of DNA from the euchromatin region of the Drosophila melanogaster X-chromosome, caused by euheterochromatin restructuring

The aim of this study was to assess the prognostic role of soluble interleukin-2 receptors (sIL-2R) in Hodgkin's disease (HD) both in the achievement of complete remission (CR) and in predicting disease relapse. Between August 1988 and June 1993 sIL-2R serum levels were measured in 174 untreated patients; in 137 of them evaluation was repeated at the end of treatment and in 132 also during the follow-up. Baseline sIL-2R levels (mean+/-standard error) were significantly higher in patients than in 65 healthy control subjects (1842+/-129 U ml(-1) vs 420+/-10 U ml(-10, P< 0.0001). At the end of treatment 135 out of 137 evaluated patients achieved complete response (CR) and their mean sIL-2R serum levels were significantly lower than those at diagnosis (635+/-19 U ml(-1) vs 1795+/-122 U ml(-1), P=0.0001). After a median follow-up of 5 years, sIL-2R remained low in 114 patients in continuous CR, while they increased in 9 out of 12 patients (75%) who relapsed. However, a temporary increase was also observed in six patients (5%) still in CR. Treatment outcome in terms of freedom from progression was linearly related to sIL-2R levels. Our study confirms that patients with untreated HD have increased baseline levels of sIL-2R compared with healthy subjects and that their pretreatment values may be an indication of disease outcome similar to other conventional prognostic factors, such as number of involved sites, presence of B symptoms and extranodal extent.     

Processing of the Ebola virus glycoprotein by the proprotein convertase furin

In the present study, we have investigated processing and maturation of the envelope glycoprotein (GP) of Ebola virus. When GP expressed from vaccinia virus vectors was analyzed by pulse-chase experiments, the mature form and two different precursors were identified. First, the endoplasmic reticulum form preGPer, full-length GP with oligomannosidic N-glycans, was detected. preGPer (110 kDa) was replaced by the Golgi-specific form preGP (160 kDa), full-length GP containing mature carbohydrates. preGP was finally converted by proteolysis into mature GP1,2, which consisted of two disulfide-linked cleavage products, the amino-terminal 140-kDa fragment GP1, and the carboxyl-terminal 26-kDa fragment GP2. GP1,2 was also identified in Ebola virions. Studies employing site-directed mutagenesis revealed that GP was cleaved at a multibasic amino acid motif located at positions 497 to 501 of the ORF. Cleavage was blocked by a peptidyl chloromethylketone containing such a motif. GP is cleaved by the proprotein convertase furin. This was indicated by the observation that cleavage did not occur when GP was expressed in furin-defective LoVo cells but that it was restored in these cells by vector-expressed furin. The Reston subtype, which differs from all other Ebola viruses by its low human pathogenicity, has a reduced cleavability due to a mutation at the cleavage site. As a result of these observations, it should now be considered that proteolytic processing of GP may be an important determinant for the pathogenicity of Ebola virus.