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PubMed2005

A study of TRAIL receptors in squamous cell carcinoma of the head and neck.

OBJECTIVE: To determine the potential immediate applicability of tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and TRAIL-R2, the apoptotic forms of TRAIL-Rs, for preclinical testing. DESIGN AND SETTING: Head and neck squamous cell carcinoma (HNSCC) tumors were studied for TRAIL-R1 and TRAIL-R2 expression by immunohistochemical analysis. In addition, matched tumor and peripheral blood DNA samples were screened for 2 known TRAIL-R1 coding single nucleotide polymorphisms (C626G and G422A). Subjects Tumor samples taken from 43 patients (37 samples for immunohistochemical analysis and 6 additional ones included for polymorphism analysis). MAIN OUTCOME MEASURES: The expression of TRAIL-R1 and TRAIL-R2 and the presence of the TRAIL-R1 polymorphisms C626G and G422A. RESULTS: Fewer than 25% of HNSCC tumor cells expressed TRAIL-R1 and TRAIL-R2. Surrounding tumor-infiltrating polymorphonuclear cells expressed TRAIL-R1 and TRAIL-R2 in 12 (32%) and 14 (38%) of cases, respectively. The TRAIL-R1 polymorphisms C626G and G422A were present in 36 (88%) and 33 (89%) cancer cases, respectively. Compared with control groups from another study, these polymorphism frequencies were statistically significant (P = .01 and .003, respectively). CONCLUSIONS: TRAIL-R expression was detected in less than half of the tumor specimens studied but not in any surrounding normal tissue and was found in a higher frequency on tumor-infiltrating polymorphonuclear cells than on tumor cells. These findings support the idea that the presence of TRAIL-Rs on some HNSCC tumors may make them more susceptible to apoptosis, and they also suggest that TRAIL-R-associated mechanisms may result in immune-modulatory effects on tumor-infiltrating polymorphonuclear cells. Furthermore, the significant association of somatic TRAIL-R1 genetic polymorphisms in this sample of patients with HNSCC suggests a potential association between constitutive TRAIL-R1 polymorphisms and development of HNSCC. Defining TRAIL-R expression and genetic polymorphisms in HNSCC represents the first step in examining TRAIL-related mechanisms for their potential as therapeutic targets.

Apoptosis Regulatory Proteins↗
PubMed1993

Assessment of frontal lobe functioning in schizophrenia and unipolar major depression.

This study has used neuropsychological tasks--Wisconsin Card Sort (WCST), Trail Making (TMT) A and B, Verbal Fluency, Digit Span--to compare acute and currently off-medication schizophrenics, patients with unipolar nonpsychotic major depression and healthy controls. Both patient groups differed significantly from healthy controls in their neuropsychological performance. Furthermore there was only little (quantitative) difference between schizophrenics and depressed patients in the frontal lobe associated tasks: WCST, TMT and Verbal Fluency. Depressed patients tended to perform worse than schizophrenics on Digit Span, a task hypothesized to involve other than frontal areas of the brain. Although the group of depressed patients was older than the schizophrenic sample, the effect of age may not totally explain the findings. The results indicate that there do exist disturbances in frontal lobe cognitive functioning in schizophrenia and depression. Symptomatology (SANS/SAPS) and cognitive functioning in the schizophrenic group revealed only a trend for negative symptoms to be associated with worse performance in the WCST, but were significantly correlated with negative as well as positive symptoms on the TMT.

Adult↗
PubMed1999

Use of a handheld, battery-operated chemistry analyzer for evaluation of heat-related symptoms in the backcountry of Grand Canyon National Park: a brief report.

STUDY OBJECTIVES: To test the feasibility of using handheld, battery-operated chemical analyzers by EMS personnel in a wilderness environment to aid in the diagnosis and management of heat illness. METHODS: During the summer of 1996, 3 portable clinical analyzers (i-STAT Corp, Princeton, NJ) were kept at different locations along the main hiking trail into the Grand Canyon. An operational protocol was designed for field use, and Park Service EMS personnel used the instruments at their discretion, primarily to determine serum sodium concentration and identify cases of hyponatremia. Data were collected on all EMS encounters. This study reviews our experience with the instruments. RESULTS: The i-STAT analyzer was used for 64 patients in the backcountry; of these uses, at least 22 were in the field and the remainder in backcountry ranger stations. Eight error messages were recorded in 6 patients. Subsequently, all but 1 had a successful determination. Among patients evacuated for further evaluation and care, serum sodium values were highly consistent with later analysis using standard laboratory equipment. The instrument was used in 31 (48%) of 64 of patients evaluated and released for self-treatment and self-evacuation, and 31 (36%) of 87 of patients evacuated by EMS personnel from the canyon. Nine cases of hyponatremia were confirmed in the field, allowing appropriate intervention. CONCLUSION: Portable clinical analyzers can reliably be used in a hot wilderness environment. In our application, it allowed identification of exercise-associated hyponatremia, an important cause of serious heat illness during endurance exercise in a hot environment. The results helped make treatment and disposition decisions.

Arizona↗
PubMed1990

ON-OFF units in the mustached bat inferior colliculus are selective for transients resembling "acoustic glint" from fluttering insect targets.

Of 311 single units studied in the central nucleus of the inferior colliculus (ICC) in 18 mustached bats (Pteronotus parnelli), a small but significant population (13%) of cells with on-off discharge patterns to tone bursts at best frequency (BF) was found in the dorsoposterior division. In contrast to units with the same BF's but other discharge patterns, the majority of ON-OFF units were unresponsive to sinusoidally amplitude-modulated tone bursts (SAM). To define the contribution of linear and nonlinear components to the responses of ICC neurons to amplitude modulation, we tested some of these neurons with a long, seamlessly repeating pseudorandom sequence of ternary amplitude-modulated tones at BF. Wiener-like kernels were subsequently derived from cross-correlation of spikes with acoustic events in the sequence. These kernels provided estimates of neural impulse responses that proved unusual in SAM-unresponsive ON-OFF units. First, their estimated impulse response had no linear component. Second, the predicted second-order impulse responses to both increments and decrements in stimulus intensity were long (about 20 ms) and nearly identical in shape: triphasic, with the positive phase bounded by leading and trailing negative periods. The similar shape of responses to increments and decrements in these neurons suggests a full-wave rectifier. The triphasic, initially negative second-order prediction of the impulse response accounted for an unusual result in experiments measuring the recovery cycle of ON-OFF units using a pair of identical stimulus pulses separated by various time delays. This recovery cycle can be related to their response to amplitude modulation. As the delay between two brief, near-threshold BF tone bursts decreased, the response to the first tone diminished, rather than to the second. The second-order prediction of this experiment derived from impulse responses obtained with pseudorandom noise suggests that, at short interpulse intervals, the initial negative phase of the response to the later stimulus cancels the positive phase of the response to the first. Such cancellation at short interpulse intervals may help explain why the majority of ON-OFF units are unresponsive to SAM. The unusual properties of these ON-OFF units make them ideally suited to respond selectively to infrequent acoustic transients superimposed on an ongoing background of modulation. Such patterns are commonly encountered by mustached bats foraging in cluttered habitats for small, fluttering insects, which generate "acoustic glints" upon a background of modulated echoes from the surroundings (Schnitzler et al. 1983; Henson et al. 1987).

Acoustic Stimulation↗
PubMed2006

Animal models for vaccine studies for visceral leishmaniasis.

Visceral leishmaniases (VL) or kala-azar is the most dreaded and devastating amongst the various forms of leishmaniases. The disease, though localized in certain areas only, has gained immense importance because of high mortality rate, mainly in children. The parasite is responsible for a spectrum of clinical syndromes, which can, in most extreme cases, go from an asymptomatic infection to a fatal form of VL. Chemotherapeutic measures, alone are not sufficient to control and contain the disease. As an alternate strategy, vaccination is also under experimental and clinical trails. The situation unquestionably demands the use of proper screening system, rationale chemical synthesis, vaccine development and targeted vaccine delivery. Thus, development of an acceptable vaccine is not an easy task. While the factors, which determine clinical outcomes, are in part, a feature of the parasite, it is the nature of the host and its genetic make up and immune status that play crucial role. The prerequisite of reliable animal model is that it should have a considerably good correlation with the clinical situation and is expected to mimic the pathological features and immunological responses observed in humans when exposed to a variety of Leishmania spp. with different pathogenic characteristics. Many experimental animal models like rodents, dogs and monkeys have been developed, each with specific features, but none accurately reproduces what happens in humans. In addition to the nature of the host, the major difference between natural and experimental infections is the parasite inoculum; in natural conditions, the infected sand fly vector deposits a few hundred metacyclic promastigotes into the dermis of the host, whereas experimental infections are induced by the injection (subcutaneous or intravenous) of millions of promastigotes grown in axenic cultures in vitro or amastigotes recovered from infected spleens. In public health terms, VL is the disease of humans and dogs (which may be considered secondary or 'accidental' hosts in the leishmanial life cycle) who often exhibit severe clinical signs and symptoms when infected, whereas reservoir hosts generally show a few, minor or no signs. This situation makes the definition of a suitable laboratory model a difficult one since the various experimental hosts may behave either like a reservoir or an accidental host. This review discusses the concept of animal models for VL and provides a critical evaluation of the most common experimental models and their respective advantages and disadvantages. Particular emphasis is given to the value of using mouse, hamster, dog and primate models, especially in the context of testing potential antileishmanial vaccines.

Animals↗
PubMed2001

Neurocognitive performance enhanced by highly active antiretroviral therapy in HIV-infected women.

OBJECTIVE: To determine whether highly active retroviral therapy (HAART) is associated with better neurocognitive outcome over time among HIV-infected women with severely impaired immune function. METHODS: A semiannual neurocognitive examination on four tasks was administered: Color Trail Making, Controlled Oral Word Association, Grooved Pegboard and Four-Word Learning. This protocol was initiated in the HIV Epidemiological Research study (HERS) study when a woman's CD4 cell count fell to < 100 x 10(6) cells/l. Immune function (CD4), viral load status and depression severity (CESD) were also assessed semi-annually, along with an interview to determine medication intake and illicit drug use. RESULTS: HAART was not available to any participant at the time of enrollment (baseline), while 44% reported taking HAART at their most recent visit (mean duration of HAART 36.3 +/- 12.6 months). HAART-treated women had improved neurocognitive performance compared with those not treated with HAART. Women taking HAART for 18 months or more showed the strongest neurocognitive performance with improved verbal fluency, psychomotor and executive functions. These functions worsened among women not taking HAART. Substance abuse status, severity of depressive symptoms, age and educational level did not influence the HAART treatment effects on neurocognitive performance. Neurocognitive improvements were strongly associated with the magnitude of CD4 cell count increases. CONCLUSIONS: HAART appeared to produce beneficial effect on neurocognitive functioning in HIV-infected women with severely impaired immune systems. Benefits were greatest for women who reported receiving HAART for more than 18 months.

Adolescent↗
PubMed2002

Attention deficits are not characteristic of schoolchildren with newly diagnosed idiopathic or cryptogenic epilepsy.

PURPOSE: To compare problems of attention in schoolchildren with newly diagnosed idiopathic or cryptogenic epilepsy with those in healthy classmates. METHODS: A computerized battery of tasks comprised Reaction Time (RT) measurement, Trail making (Color Trails 1 and 2), Manual Tapping and Steadiness, and a newly developed task of sustained attention (Balloon Piercing). SUBJECTS: Fifty-one children with epilepsy (age 7-16 years) and 48 gender- and age-matched classmates were assessed thrice: within 48 h after diagnosis [before start of antiepileptic drugs (AEDs)], and 3 and 12 months later. Significantly more children with epilepsy (51%) than control children (27%) had required special educational assistance at school. RESULTS: Children with epilepsy could not be distinguished from controls in execution times or motor speed. However, errors were more frequent among patients in a "go-no-go" RT task, and errors of omission in a task requiring sustained attention. Within the group of children with epilepsy, those with prior school or behavior difficulties and those whose parents reacted maladaptively to the onset and diagnosis of epilepsy performed worse than those without these adversities, in the sense that their RT increased inordinately with increasing task difficulty. Epilepsy-related variables did not explain any variance. Transient inordinately poor performances were found in 69% of patients and 40% of controls. CONCLUSIONS: Children with newly diagnosed "epilepsy only" do not have persistent attention deficits. AED treatment has no detrimental effect on attention. Prior school and behavior difficulties and a maladaptive reaction to the onset of epilepsy rather than epilepsy variables are related to decreased attentional efficiency.

Attention↗