Dysregulated Fas and Bcl-2 expression leading to enhanced apoptosis in T cells of multiple myeloma patients

We have previously reported the presence of activated (HLA-DR+) T cells in multiple myeloma (MM) patients. These cells produce high amounts of interleukin (IL)-2 and interferon (IFN)-gamma and generate a potent antiplasma cell activity after appropriate in vitro stimulation, but they are unable in vivo to hold in check the disease. Activated T cells are highly susceptible to apoptosis, a form of programmed cell death involved in the modulation of immune responses and regulated by molecules such as Fas (CD95) and bcl-2. The aim of this study was to determine the expression of Fas and bcl-2 antigens and the susceptibility to apoptosis in T cells of MM patients. Fas+ cells were significantly higher, whereas bcl-2+ cells were significantly lower in MM patients than in the controls. MM patients with the highest number of HLA-DR+ T cells showed the highest Fas and the lowest bcl-2 expression. Two-color cytofluorometric analysis confirmed in individual cells that HLA-DR+ T cells coexpressed Fas and lacked bcl-2. Susceptibility to apoptosis was then investigated to evaluate the consequence of dysregulated Fas and bcl-2 expression. The percentage of apoptotic cells after incubation in medium alone (spontaneous apoptosis) or in the presence of methylprednisolone (MP) or anti-Fas monoclonal antibody (triggered apoptosis) was significantly higher in MM and mainly restricted to HLA-DR+ T cells. Spontaneous apoptotosis was reverted by exogenous IL-2. In conclusion, MM T cells have a dysregulated expression of Fas and bcl-2 antigens that is associated with an enhanced susceptibility to apoptosis. These data may unravel a novel mechanism by which activated MM T cells are weakened in their ability to exert an effective antitumor activity in vivo.     

Localized proton magnetic resonance spectroscopy of a cerebellar tumor in a two-year-old child

Noninvasive localized proton magnetic resonance spectroscopy (MRS) was used for differential diagnosis of a focal brain lesion in a 2.5-year-old girl. The clinical signs were a mild head tilt and neck pain. Magnetic resonance imaging (MRI) revealed a lesion in the right hemisphere of the cerebellum, but its nature remained obscure. In this lesion quantitative determinations of cerebral metabolites by fully relaxed, short-echo-time proton MRS revealed markedly lowered N-acetylaspartate (NAA) and pronounced elevations of choline-containing compounds (Cho) and myo-inositol (Ins), whereas metabolite concentrations in cortical gray matter and white matter were within normal ranges. The metabolite pattern of the lesion indicated loss of vital neuroaxonal tissue (low NAA) and enhanced glial proliferation (high Cho and Ins), which, together with the MRI morphology, suggested a brain tumor. The diagnosis was established by neurosurgical exploration and total extirpation of the tumor. Histology confirmed an astrocytoma (WHO II). After 2 weeks' recovery the child was discharged with no neurological signs.     

Receptor-dependent regulation of the concentration of Ca2+ in the cytoplasm of thrombocytes in hypertensive patients

Platelet activation factor (PAF)-, ADP and vasopressin-induced increments of platelet Ca2+ concentration were measured by quin-2 in 64 patients with essential hypertension and 16 normal donors. Basal concentration of free Ca2+ was 87 +/- 4 nM in donors, 106 +/- 5 nM in patients with labile hypertension (LH) and 122 +/- 6 nM in those with stable hypertension (SH) (p less than 0.01). PAF, ADP and vasopressin, added to platelets, increased [Ca]in by 448 +/- 58, 397 +/- 66, and 277 +/- 50 nM, respectively, in the donors, by 473 +/- 57, 479 +/- 54 and 195 +/- 32 nM, in LH patients, and by 607 +/- 85, 584 +/- 73 and 245 +/- 41 nM in SH patients. There were no significant variations between the three samples, using the ANOVA test. In 20 patients, whose both parents had essential hypertension, [Ca]in increment was 738 +/- 8 nM for PAF, 682 +/- 90 nM for ADP, and 320 +/- 61 nM for vasopressin. In 19 patients, who admitted to no essential hypertension in the family, these parameters were significantly lower: 310 +/- 40 nM for PAF, 389 +/- 61 nM for ADP, and 147 +/- 26 nM for vasopressin. The demonstrated changes may be making an important contribution to the maintenance of elevated vascular tone and provide an evidence in favor of a genetically-predetermined EH variety.     

Study on the lymphatic flow of the lower gastric region for radical lymphadenectomy in advanced lower gastric cancer

A prognosis of patients with a curative resected advanced cancer of the lower gastric region was worse than that of the other region of the stomach. The 5 year survival rate was only 47.3%. One of the main reasons was that a rate of lymph node recurrence was higher. In this point of view, we studied on lymphatic flow of the lower gastric region using an activated carbon particle (CH40). Lymph nodes were stained black soon after the injection of CH40 into the lower gastric wall at laparotomy. The black stained rate of an each regional lymph node was as follows. 3. 58%, 4. 17%, 5. 50%, 6. 25%, 1. 21%, 7. 58%, 8. 83%, 9. 58%, 11. 17% and 12. 33% in case of injection into the greater curvature and and 4. 31%, 6. 100%, 8. 25%, 9. 25%, 14V and 56% in case of injection into the lesser curvature. The stained rate was relatively high in 12 and 14V lymph node which we had not routinely dissected. The rates of lymph nodes stained black were related to those of cancer metastasis. The results suggest that lymphadenectomy of 12 for the cancer at the lesser curvature and that of 14V for the cancer at the greater curvature might make a prognosis of lower gastric cancer better.     

Confounders contributing to the reported associations of coffee or caffeine with disease

The role of caffeine or coffee in causing or promoting the incidence of serious disease is equivocal. Two design factors may account for the discrepancies in reported findings on the effects of coffee drinking: (a) imprecision of measurement and (b) confounding variables. A study of 2,714 white U.S. adults disclosed that, of 32 risk factors analyzed by linear and logistic regression, only sex and cigarette smoking were found to be important potential confounders of caffeine and coffee intake. Partial R2 values of the other 30 risk factors were relatively small and were inconsistent for each sex. It is unlikely that any of these factors could explain any of the reported associations between caffeine or coffee consumption and certain diseases. However, certain weak associations with caffeine or coffee intake should be included in the study design when they are known to be risk factors of a disease under investigation. These factors for men are dietary fat intake, vitamin C intake, and body mass index; and for women are vitamin use, alcohol intake, stress, and perceived health status.