A novel cysteine cathepsin inhibitor yields macrophage cell death and mammary tumor regression.

Although cysteine cathepsins have been identified as key regulators of cancer growth, their specific role in tumor development remains unclear. Recent studies have shown that high activity levels of tumor cathepsins are primarily a result of increased cathepsin activity in cancer-promoting tumor-associated macrophages (TAMs). To further investigate the role of cysteine cathepsin activity in normal and polarized macrophages, we established in vitro and in vivo models of macrophage differentiation and polarization and used a novel cysteine cathepsin inhibitor, GB111-NH2, to block the activity of cathepsins B, L and S. Here we show that in vitro, cysteine cathepsin inhibition yields both apoptosis and proliferation of macrophages, owing to increased oxidative stress. Proteomic analysis of cathepsin- inhibited macrophages demonstrates inhibition of autophagy, suggesting a likely cause of elevated reactive oxygen species (ROS) levels. In vivo models of mammary cancer further show that cathepsin inhibition yields TAM death owing to increased ROS levels. Strikingly, apoptosis in TAMs yields a seemingly cell non-autonomous death of neighboring cancer cells, and regression of the primary growth. These results show that cysteine cathepsin inhibitors can specifically trigger macrophage cell death and may function as an effective anticancer therapy in tumors with high levels of TAMs.

Word fluency in aging and dementia: principles of relatedness in the generative naming process.

Nineteen elderly people, some healthy, some Alzheimer patients, were given the Word Fluency Test. Their responses were correlated with several personal variables such as age, years of education, Mini-Mental-State score, etc. The responses were also analyzed in terms of types and percentage of word relatedness. It was found that the total number of response words, new words and percentage of word relatedness, correlates with the Mini-Mental-State score only. However, the degree of significance of the various correlations indicates a differential deterioration slope for various principles of relatedness. Results are discussed within the framework of semantic memory and its organizational principles.

The use of organizational principles in naming generation: its relation to time-dependency in normal elderly and Alzheimer patients.

Nineteen elderly--ten healthy and nine Alzheimer patients--were given a naming-generation task. Their responses were analyzed according to word-type and inter-word relatedness. The results were correlated with the Mini-Mental-State Examination (MMSE) and examined to elucidate time-dependency. In healthy subjects it was found that time-dependency exists for the number of new words and for percent of phonetically-related words, while for Alzheimer patients, time-dependency was exhibited in new words only. Results are discussed in terms of the principles of semantic-memory organization and time-dependency of cognitive-linguistic functions.

Pupillary block glaucoma due to residual perfluoro-decalin.

Perfluorocarbon liquids are used in vitreoretinal surgery and should be removed by the end of surgery. Removal is not always achieved and a few cases of complications resulting from perfluorocarbon liquid residues have been reported. The authors report a unique case of pupillary block glaucoma resulting from perfluoro-decalin residue in the anterior chamber that blocked a surgical coloboma of the iris at the 6-o'clock position. The perfluoro-decalin residue dissolved spontaneously with antiglaucoma treatment and no surgical intervention was needed. When perfluorocarbon liquids are used during pars plana vitrectomy, the possibility of silicone-induced pupillary block in the presence of an inferior iris coloboma should not be overlooked.

Survival rate and 2 year outcome in very low birthweight infants.

The purpose of this study was to determine the mortality rate of 282 infants with a birthweight (BW) of < 1,500 g during a 5 year period (1987-92), and to evaluate 2 year neurodevelopmental outcome in 114 infants (born 1987-90) and its correlation with intracranial pathologies diagnosed by ultrasonography. Overall survival rate was 76.6% (216/282). With the introduction of exogenous surfactant therapy in 1991 a significant increase in survival was noted in the 751-1,000 g BW infants (from 20/36 to 20/22, P < 0.002). Two year evaluation was performed in 114 of 119 infants (95.7%) who survived this age. Twenty-two children (22/114, 19.3%) were functionally disabled, of whom 15 (13%) had a major disability. Of these 15 infants, 5/28 weighed < 1,000 g and 10/86 weighed 1,001-1,500 g (P = 0.6). Severe intraventricular hemorrhage (IVH) and cystic periventricular leukomalacia (PVL) were significantly associated with adverse outcome at 2 year (5/11 and 10/10 respectively were handicapped, P < 0.001). We therefore conclude that every effort should be made to save the extremely premature infants (< 1,000 g BW). Since adverse outcome was significantly associated with severe brain pathologies (large IVH and cystic PVL) rather than with lower BW, brain ultrasonography as a diagnostic mode should be taken into clinical consideration.

The Gulf War: pediatric emergency room function.

PURPOSE: To analyze the effects of war on the civilian population through patterns of medical service consumption in a pediatric emergency room. METHODOLOGY: A survey of variables related to use of emergency room services before, during, and after the Gulf War. RESULTS: There was a dramatic decrease in the number of visits during the war. During the war, there were fewer visits for URI, home accidents and intoxications; there were more visits for complaints such as headaches, restlessness, and tremors. CONCLUSIONS: Visits during the ware were more related to emergency situations with fewer visits of the walk-in clinic type.

Toward a clinical subgrouping of hyperactive and nonhyperactive attention deficit disorder. Results of a comprehensive neurological and neuropsychological assessment.

We studied 32 boys with attention deficit disorder (ADD)--21 with hyperactivity, and 11 without hyperactivity. The ADD group with hyperactivity had significantly more neurological and cognitive abnormalities and a higher frequency of prenatal and neonatal abnormalities. It seems that hyperactivity is an important determinant of the degree of neurological and cognitive involvement in children with ADD. It also seems that a cause of "early" brain insult is more likely when hyperactivity is present.

The use of pupillometry in the study of on-line verbal processing: evidence for depths of processing.

The effect of context and task demand upon the perception and resolution of lexical ambiguities was investigated in three experiments using pupillary measurements. Sentence type (ambiguous, disambiguous, and control) was tested under three conditions ("recall," "define word," and "choose best meaning"). All types of ambiguous sentences had higher pupillary curves than unambiguous sentences, with a particularly sharp rise in pupil size following the homophone. In addition, differences were observed in total sentence rise among the three task demands, such that the definition task was higher than recall, while the "choice" task exhibited a continuing rise after the sentence, which both other tasks did not have. Results are discussed in relation to putative processing stages of sentences, such as lexical search and sentence integration, and the more general issue of depths of processing.

The phonemic analysis as a treatment method in dysgraphic aphasic patients.

Two theories have been advanced to explain the underlying process of writing acquisition. The first sees a global registration of whole words in a pictorial (graphic) form; the second is based on an analysis synthesis process of each word into its sound (phonemes), and the translation of each phoneme into its graphic form (grapheme). This paper, derived from the latter theoretical construct, attempts to show that phonemic analysis-synthesis is also an efficient approach in the rehabilitation of dysgraphic aphasics. 51 patients at the Loewenstein Rehabilitation Center--31 post C.V.A. and 20 post C.C.I. were taught to write using this method, and their improvement was tested and analysed within 6 months after the event. It is shown that they all improved significantly, although the various syndrome sub-groups behaved differently. The implications of these differences and the total results are discussed.