Tetrahydroaminoacridine increases acetylcholine synthesis and glucose oxidation by mouse brain slices in vitro

1,2,3,4-Tetrahydro-5-aminoacridine (THA; tacrine) reportedly improves cognitive deficits in certain individuals with Alzheimer's disease. The present study describes increased glucose oxidation and acetylcholine (ACh) synthesis by mouse brain slices after THA treatment. THA increased [U-14C]glucose decarboxylation and ACh formation in a concentration-dependent manner in hippocampal slices (50 nM less than 50 microM less than microM). In striatal and cortical slices, 50 microM THA effectively elevated the oxidation of glucose and its incorporation into ACh. Thus the efficacy of THA treatment on Alzheimer patients may be partially related to increased ACh synthesis and oxidative metabolism.     

Comparison of the radiosensitivity of interleukin-2 production between species, between tissues, and between young and old individuals

The radiosensitivity of interleukin-2 (IL-2) production was assessed of (a) peripheral blood mononuclear cells (PBMC) of young humans, dogs, and mice (C57BL/6); (b) PBMC and splenic cells of young mice; and (c) PBMC of young and old humans and the splenic cells of young and old mice. The results indicate that (a) large differences in radiosensitivity exist between the PBMC of humans, dogs, and mice (e.g., the radiation doses which resulted in 37% remaining IL-2 activity (D37) of human, dog, and mouse PBMC were 3771, greater than 10,000, and 1398 rads, respectively); (b) only a small difference exists between the PBMC and splenic cells of mice; and (c) no difference exists between the PBMC of young and old humans and between splenic cells of young and old mice. Topological abnormalities, as judged by scanning electron microscopic analysis, could not be detected in dog PBMC after their exposure to 1800 rads, but could be detected in mouse PBMC after their exposure to 400 rads.     

Eosinophil activation in allergic disease

The eosinophil granulocyte is a pro-inflammatory cell which in its granules contains an abundance of highly cytotoxic proteins such as eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, eosinophil protein X and major basic protein. Upon stimulation of the cell, these proteins as well as a number of lipid mediators such as leukotriene C4, prostaglandin and platelet-activating factor are released to the exterior. The molecules which are produced during inflammatory reactions of the allergic type attract eosinophils to the target organ and stimulate them to liberate their products. The physiological meaning of this reaction is probably to combat invading parasites; however, in their absence accumulation and activation of eosinophils may cause disease, and one such disease may be chronic asthma.     

Transient atypical lymphocytosis in patients with emergency medical conditions

Lymphocytosis in older adults is unusual and frequently indicates chronic lymphocytic leukemia or other lymphoproliferative disorder. This report describes 73 patients, aged 43 to 93 years, who presented with emergency medical conditions and who had absolute lymphocytosis, with absolute lymphocyte counts ranging from 4.1 to 12.9 X 10(9)/L (4100 to 12,900/mm3). The lymphocytosis was characterized morphologically by atypical lymphocytes and was transient, followed, in most instances, by a neutrophilia. Most of the patients presented with serious cardiac conditions; the remaining presented with other critical disorders including status epilepticus and traumatic injuries. The mortality rate was high (50%). The lymphocytosis in some patients was probably secondary to the administration of epinephrine. The lymphocytosis in those not receiving epinephrine may have represented a physiologic reaction to severe stress.     

Mammalian transforming growth factor beta1 activated after ingestion by Anopheles stephensi modulates mosquito immunity

During the process of bloodfeeding by Anopheles stephensi, mammalian latent transforming growth factor beta1 (TGF-beta1) is ingested and activated rapidly in the mosquito midgut. Activation may involve heme and nitric oxide (NO), agents released in the midgut during blood digestion and catalysis of L-arginine oxidation by A. stephensi NO synthase (AsNOS). Active TGF-beta1 persists in the mosquito midgut to extended times postingestion and is recognized by mosquito cells as a cytokine. In a manner analogous to the regulation of vertebrate inducible NO synthase and malaria parasite (Plasmodium) infection in mammals by TGF-beta1, TGF-beta1 regulates AsNOS expression and Plasmodium development in A. stephensi. Together, these observations indicate that, through conserved immunological cross talk, mammalian and mosquito immune systems interface with each other to influence the cycle of Plasmodium development.     

Low density lipoprotein receptor activity in human leukemic cells--relation to chromosome aberrations

Chromosome analysis and low density lipoprotein (LDL) receptor activity of leukemic cells from 38 patients with acute non-lymphocytic leukemia were correlated. Clonal chromosome aberrations were found in 22 patients, and an extra chromosome 8 was found in 7 of them. LDL receptor activity was significantly higher in patients with an extra chromosome 8 than in patients with other abnormalities or a normal karyotype. Chromosome 8 may harbor genes of importance for the expression of the LDL receptor.     

Alternate Pathway Activation in Sickle Cell Disease and ��-Thalassemia Major

Total hemolytic complement activity (CH50), immuno-electrophoretic conversion of Factor B (C3PA), and of C3 were studied in 16 patients with sickle cell disease in a steady state, eight patients in crisis, and ten patients with β-thalassemia major anemia maintained on a constant transfusion regimen. Patients with sickle cell disease in a steady state have moderatley 56 (percent) depressed conversion of Factor B in addition to markedly decreased conversion of C3 in four of ten patients. One of the three sickle cell patients and two of the four thalassemia patients with low C3 conversion levels have died subsequent to the studies. The combination of chronically decreased Factor B conversion in the face of markedly decreased C3 conversion may make these patients occasionally vulnerable to overwhelming infection analagous to the situation seen in postsplenectomy cases.     

Familial testicular cancer: interest in genetic testing among high-risk family members.

PURPOSE: This study is part of an ongoing National Cancer Institute multidisciplinary, etiologically-focused, cross-sectional study of Familial Testicular Cancer (FTC). The current report targets interest in clinical genetic testing for susceptibility to FTC. METHODS: Demographics, knowledge, health beliefs, and psychological and social factors were evaluated as covariates related to interest in genetic testing. RESULTS: The majority (66%) of 229 participants (64 affected men, 66 unaffected men, and 99 women) from 47 multiple-case FTC families expressed interest in having a genetic test within 6 months, should such a test become available. Interest was similar among the three subgroups mentioned above. Worries about insurance discrimination based on genetic test results were associated with a significantly lower interest in testing. Alternatively, participants were more likely to be interested in genetic testing if they were younger and had higher levels of family support, a physician's recommendation supporting testing, cancer distress, and a need for information to inform the health care of their children. CONCLUSIONS: This study reveals social and relationship factors that FTC survivors and their relatives considered important when contemplating the use of new genetic technologies. This is the first study describing hypothetical interest in genetic testing for familial testicular cancer.     

Indirect evidence of bronchial inflammation assessed by titration of inflammatory mediators in BAL fluid of patients with asthma

Bronchial inflammation is a characteristic of asthma that may be examined indirectly by bronchoalveolar lavage (BAL). Nine normal individuals were compared with 38 age-matched adults with asthma of variable severity to appreciate the importance of cell activation in the severity of asthma. The severity of asthma was appreciated by the clinical score of Aas and the pulmonary function of the patients. FEV1 ranged between 35% and 130% of predicted. The indirect activation of eosinophils (EOSs), mast cells, fibroblasts, and neutrophils was examined by the titration of eosinophil cationic protein (ECP), tryptase, hyaluronan (HA), and myeloperoxidase (MPO) by radioimmunoassay in BAL fluid (BALF) and cytology of BALF. In the adults with asthma, there was a significantly increased number of EOSs and a significantly increased level of all mediators but MPO. MPO levels were increased in seven patients only; three of these patients were previous smokers. Only ECP and HA levels were significantly correlated with the severity of asthma. These results demonstrate EOSs, mast cells, and fibroblasts are activated in asthma, whereas the involvement of neutrophils is less clear. There was a significant correlation between ECP and HA levels, suggesting a common activation of EOSs and fibroblasts.