Human soluble tumor-associated antigens promote the suppression of rat mammary tumors by 5-fluorouracil and stimulate the functional activity of immune organs: Experimental and morphological studies

This study examined whether the soluble 66 and 51 kDa tumor-associated antigens (sTAA) could promote suppression by the anticancer drug 5-fluorouracil (5-Fu) of chemically induced mammary tumorigenesis, and which, if any, morphological changes in the immune organs accompany this treatment. Dimethylbenzanthracene (DMBA, 8 mg/rat, twice) was used to induce mammary tumors. After the appearance of many large tumors, the preparations of sTAA and 5-Fu, alone or in combination, were administered in weekly doses, for 4 weeks. The following groups of mammary tumor-bearing rats were studied: 1) control non treated rats, 2) rats treated with sTAA, 3) rats treated with 5-Fu, 4) rats treated with 5-Fu and sTAA. The experiment was terminated when tumors in 70% of control rats became ulcerous. Treatment with sTAA alone significantly decreased tumor yield and their total area relative to controls. Both of these parameters showed an even larger significant decrease after treatment with 5-Fu, and the most marked decrease was obtained after the combined treatment with 5-Fu and sTAA. Results demonstrated that not only do sTAA have tumor-suppressive properties, they also enhance the anticancer effects of 5-Fu and prevent its toxic side effects. Morphologically, the treatment with sTAA was manifested in a significant increase in the size of the spleen follicles and mantle layer compared to control rats with large tumors. The treatment with 5-Fu decreased the sizes of almost all areas of the spleen compared to control rats, whereas the combined treatment with 5-Fu and sTAA increased all these parameters to the levels found in rats treated with sTAA alone. The total areas of the cortex and paracortex in the lymph nodes increased after treatment with sTAA. Treatment with 5-Fu alone resulted in a significant decrease of these areas which, as seen in the spleen, increased after combined treatment with 5-Fu and sTAA. Similar changes were seen in the areas of the separate lymph node zones. We concluded that the addition of sTAA to conventional tumor chemotherapy regimens has a remarkable synergistic effect on mammary tumors leading to curative antitumor responses of the host's immune organs.     

Imaging Trypanosoma cruzi within tissues from chagasic patients using confocal microscopy with monoclonal antibodies

Confocal fluorescence microscopy combined with differential interference contrast imaging of tissues from chagasic patients enabled the unequivocal identification of the parasite Trypanosoma cruzi. Using different monoclonal antibodies that indicate the parasite form and replication stage in conjunction with DNA labelling, specimens derived from distinct clinical forms of the disease were examined. Intracellular amastigote forms of the parasite were clearly detected in heart, brain, skin, lung, and kidney. Dividing amastigotes as well as trypomastigote forms were recognized in samples obtained from patients undergoing either acute-phase or some form of reactivation caused by immunosuppression. Received: 22 December 1998 / Accepted: 11 March 1999     

Effects of tamoxifen and soluble tumor-associated antigens on ovarian structure in mammary tumor-bearing rats

Previously, we showed that the 66 and 51 kDa soluble tumor-associated antigens (sTAAs) have distinct suppressive effects on chemically induced mammary cancer in rats, both alone and in combination with the hormone-related anticancer drug tamoxifen. Here, we describe the effects of both sTAA and tamoxifen on the histological structure of ovaries in mammary tumor-bearing 30- to 34-week-old rats. Central ovary sections were pooled, the number of the healthy and degenerated follicles were counted, and the size of the corpora lutea was estimated. In follicular development primordial, primary, preantral and antral stages were recognized. Only healthy follicles with visible nuclei were counted. Follicular degeneration was estimated as the number of atretic follicles with follicular remnants. Treatment with tamoxifen alone or in combination with sTAA significantly increased the number of primordial follicles and atretic follicles in the ovaries, and promoted the formation of small follicular cysts. Total area of the corpora lutea decreased. sTAA participated in this process by increasing apoptosis in degenerated follicles.     

Increased risk of bloodstream and urinary infections in intensive care unit (ICU) patients compared with patients fitting ICU admission criteria treated in regular wards

Critically ill patients, eligible for admission into intensive care units (ICUs), are often hospitalized in other wards due to a lack of ICU beds. Differences in morbidity between patients managed in ICUs and elsewhere are unknown, specifically the morbidity related to hospital-acquired infection. Patients fitting ICU admission criteria were identified by screening five entire hospitals on four separate days. Hospital infections within a 30-day follow-up period were compared in ICU patients and in patients on other wards using Kaplan-Meier curves. Residual differences in the patients' case mix between ICUs and other wards were adjusted for utilizing multivariate Cox models. Of 13415 patients screened, 668 were critically ill. The overall infection rates (per 100 patient-days) were 1.2 for bloodstream infection (BSI) and 1.9 for urinary tract infection (UTI). The adjusted hazard ratios in ICU patients compared with patients on regular wards were 3.1 (P<0.001) for BSI and 2.5 (P<0.001) for UTI. This increased risk persisted even after adjusting for the disparity in the number of cultures sent from ICUs compared with ordinary wards. No interdepartmental differences were found in the rates of pneumonia, surgical wound infections and other infections. Minimizing the differences between characteristics of patients hospitalized in ICUs and in other wards, and controlling for the higher frequency of cultures sent from ICUs did not eliminate the increased risk of BSI and UTI associated with admission into ICUs.     

Lymphedema of the hand following a fracture of the distal radius

A case of chronic lymphedema of the hand and forearm following a fracture of the distal radius is reported. None of the classic causes of secondary lymphedema appeared to be the cause. A strong psychogenic component appeared to be the underlying mechanism. This rare phenomenon was thought to be self-induced and not genetic in nature.     

Enhancement of thermal killing by polyamines. I. Survival of chinese hamster cells

Exposure of Chinese hamster cells to polyamines at an elevated temperature (42°C) results in synergistic cell killing. The effectiveness of polyamines in potentiating thermal killing decreases in the following order: spermine>spermidine> cadaverine>putrescine. The magnitude of the synergism increases with exposure time. The survival curves, when plotted as a function of polyamine concentration, display a shoulder during 1 h exposure at 42°C, followed by exponential cell killing. Longer exposure times eliminate the shoulder and result in steeper slopes of the survival curves. The effect is maximal when exposure to polyamines and heat is simultaneous. Separation in time between the two treatments causes a rapid disappearance of the synergism. The order of application is of only minor importance in this regard. The results suggest that the intracellular level of spermine may be a major factor in determining heat sensitivity of Chinese hamster cells.     

Role of the central amygdala in modulating the pituitary-adrenocortical and clinical responses in experimental herpes simplex virus-1 encephalitis

The amygdala is known to regulate neuroendocrine and behavioral responses to a variety of stimuli. Herpes simplex virus-1 (HSV-1) is the common cause of viral encephalitis, manifested by hypothalamic-pituitary-adrenal (HPA) axis activation, fever, hypermotor activity and aggression. We examined here the role of the central amygdala (cAMG) in regulating the HPA axis function, febrile and behavioral responses to HSV-1 infection in rats. Bilateral electrolytic lesions were performed in the cAMG. HSV-1 encephalitis was induced by intracerebroventricular (ICV) inoculation of purified virions. Motor activity and body temperature were examined by a biotelemetric system. ICV inoculation of HSV-1 caused a marked time-dependent increase in serum corticotropin (ACTH) and corticosterone at 4 and 24 h post-infection. These responses were attenuated in rats with bilateral lesions of the cAMG. HSV-1 infection induced fever, motor hyperactivity and aggressive behavior. These responses were also attenuated in rats with cAMG lesions. The cAMG plays an important role in mediating the neuroendocrine, febrile and behavioral responses to HSV-1 infection.     

Category specific dysnomia after thalamic infarction: a case-control study

Category specific naming impairment was described mainly after cortical lesions. It is thought to result from a lesion in a specific network, reflecting the organization of our semantic knowledge. The deficit usually involves multiple semantic categories whose profile of naming deficit generally obeys the animate/inanimate dichotomy. Thalamic lesions cause general semantic naming deficit, and only rarely a category specific semantic deficit for very limited and highly specific categories. We performed a case-control study on a 56-year-old right-handed man who presented with language impairment following a left anterior thalamic infarction. His naming ability and semantic knowledge were evaluated in the visual, tactile and auditory modalities for stimuli from 11 different categories, and compared to that of five controls. In naming to visual stimuli the patient performed poorly (error rate>50%) in four categories: vegetables, toys, animals and body parts (average 70.31+/-15%). In each category there was a different dominating error type. He performed better in the other seven categories (tools, clothes, transportation, fruits, electric, furniture, kitchen utensils), averaging 14.28+/-9% errors. Further analysis revealed a dichotomy between naming in animate and inanimate categories in the visual and tactile modalities but not in response to auditory stimuli. Thus, a unique category specific profile of response and naming errors to visual and tactile, but not auditory stimuli was found after a left anterior thalamic infarction. This might reflect the role of the thalamus not only as a relay station but further as a central integrator of different stages of perceptual and semantic processing.