T Cell Receptor (TCR) Engagement in Apoptosis-defective, but Interleukin 2 (IL-2)–producing, T Cells Results in Impaired ZAP70/CD3-ζ Association

We have previously shown that a tyrosine to leucine replacement in the transmembrane region of T cell receptor (TCR)-β results in a deficient induction of CD95-L and apoptosis upon TCR triggering in a transfected T cell line. By contrast, interleukin (IL)-2 production and the expression of CD25 and CD69 were normally induced. Since the mutation in TCR-β also resulted in impaired association of CD3-ζ, it was proposed that this chain is specifically required for the induction of apoptosis. We now show that the deficient induction of CD95-L and apoptosis does not derive from a general lower production of second messengers, since intracellular Ca²⁺ fluxes and tyrosine phosphorylation of total proteins were elicited at wild-type levels. Unlike in T cell clones stimulated with partial agonists, both p21 and p18 forms of tyrosine-phosphorylated CD3-ζ were detected, although the overall level of tyrosine-phosphorylated CD3-ζ was low. More strikingly, inducible association of ZAP70 to CD3-ζ was strongly inhibited, despite a normal induction of ZAP70 tyrosine phosphorylation. Finally, ZAP70 was not concentrated near the plasma membrane in the apoptosis-deficient cells. These results suggest that CD3-ζ is necessary for engagement of a specific signaling pathway leading to CD95-L expression that also needs the recruitment of ZAP70.     

Distribution of cervical metastasis in tongue cancer: Are occult metastases predictable? A retrospective study of 117 oral tongue carcinomas

Purpose

The aims of this study were to evaluate the pattern of distribution of cervical metastasis in tongue cancer and to analyze the various therapeutic options available. Moreover, numerous histological features were analyzed to assess the impact of each factor on overall survival.

The Mediterranean Diet Is Associated with a Reduction in Premature Mortality among Middle-Aged Adults

The available large prospective studies supporting an inverse association between better adherence to the Mediterranean diet and lower mortality have mainly included older adults. It is not clear whether this inverse association is also present among younger individuals at lower mortality risk. Our aim was to assess the association between adherence to the Mediterranean diet and total mortality in middle-aged adults from the Seguimiento Universidad de Navarra (SUN) Project. We followed 15,535 Spanish university graduates for a mean of 6.8 y. Their mean age was 38 ± 12 y, 59.6% were females, and all were initially free of cardiovascular disease, cancer, and diabetes. A validated FFQ was used to assess dietary habits. Adherence to the Mediterranean diet was categorized into 3 groups according to the Mediterranean Diet Score (low, 0-2 points; moderate, 3-5 points; and high, 6-9 points). The outcome variable was total mortality. Cox proportional hazards models were used to estimate HR and 95% CI. We adjusted the estimates for sex, age, years of university education, BMI, smoking, physical activity, television watching, history of depression and baseline hypertension, and hypercholesterolemia. We observed 125 deaths during 105,980 person-years of follow-up. The fully adjusted HR for moderate and high adherence were 0.58 (95% CI: 0.34, 0.99; P = 0.05) and 0.38 (95% CI: 0.21, 0.70; P = 0.002), respectively. For each 2-point increment in the Mediterranean Diet Score, the HR of death was 0.72 (95% CI: 0.58, 0.91; P = 0.006). Among highly educated, middle-aged adults, adherence to the traditional Mediterranean diet was associated with reduced risk of death.     

Short-term evolution of vasovagal syncope: influence on the quality of life

To evaluate the short-term evolution and changes in the quality of life (QoL) of patients suffering from vasovagal syncope (VVS) by the application of the Short Form 36 questionnaire (SF-36) that was prospectively administrated to all consecutive patients with syncope and abnormal response to head-up tilt test. We included 167 patients (55.7% women, median age 42 years old). During a 6-month follow-up, recurrence was observed in 33 patients (19.8%). The mean recurrence-free time was 6.2+/-0.34 months. Among those patients with and without relapses, there were only differences in the previous number of syncopes (6 vs. 3, p=0.0051). Of them, 19 (11%) only presented 1 syncopal relapse and 14 (8.2%) presented more than 1. There were differences in the time until the first relapse [4 months (2.3-5.4) vs. 1.6 months (0.8-3.3), p=0.002] and an inverse correlation between the time until the appearance of recurrences and their number (r2 Spearman=-0.54, p=0.002). In just 6 months, those patients who had recurrence had a worse QoL than those who did not, in 7 dimensions of the SF-36 questionnaire. In the short-term, one in every five patients with VVS had at least 1 relapse, and if it is very early, it can recur in up to 8% of them. The QoL of these patients is correlated with the appearance of relapses.     

Unilateral Punctate Keratitis Secondary to Wallenberg Syndrome

We studied three patients who developed left unilateral punctate keratitis after suffering left-sided Wallenberg Syndrome. A complex evolution occurred in two of them. In all cases, neurophysiological studies showed damage in the trigeminal sensory component at the bulbar level. Corneal involvement secondary to Wallenberg syndrome is a rare cause of unilateral superficial punctate keratitis. The loss of corneal sensitivity caused by trigeminal neuropathy leads to epithelial erosions that are frequently unobserved by the patient, resulting in a high risk of corneal-ulcer development with the possibility of superinfection. Neurophysiological studies can help to locate the anatomical level of damage at the ophthalmic branch of the trigeminal nerve, confirming the suspected etiology of stroke, and demonstrating that prior vascular involvement coincides with the location of trigeminal nerve damage. In some of these patients, oculofacial pain is a distinctive feature.     

Temporal Effects on Monaural Amplitude-Modulation Sensitivity in Ipsilateral,Contralateral and Bilateral Noise

The amplitude modulations (AMs) in speech signals are useful cues for speech recognition. Several adaptation mechanisms may make the detection of AM in noisy backgrounds easier when the AM carrier is presented later rather than earlier in the noise. The aim of the present study was to characterize temporal adaptation to noise in AM detection. AM detection thresholds were measured for monaural (50 ms, 1.5 kHz) pure-tone carriers presented at the onset (‘early’ condition) and 300 ms after the onset (‘late’ condition) of ipsilateral, contralateral, and bilateral (diotic) broadband noise, as well as in quiet. Thresholds were 2–4 dB better in the late than in the early condition for the three noise lateralities. The temporal effect held for carriers at equal sensation levels, confirming that it was not due to overshoot on carrier audibility. The temporal effect was larger for broadband than for low-band contralateral noises. Many aspects in the results were consistent with the noise activating the medial olivocochlear reflex (MOCR) and enhancing AM depth in the peripheral auditory response. Other aspects, however, indicate that central masking and adaptation unrelated to the MOCR also affect both carrier-tone and AM detection and are involved in the temporal effects.