Expression of high-affinity neuronal and glial glutamate transporters in the rat optic nerve

Recent studies have revealed that a dynamic axon-glial signaling occurs in the rat optic nerve, which is devoid of synapses. This interaction is postulated to be mediated by non-vesicular release of glutamate via a reversal of high-affinity glutamate transporters. Here we examined the expression of glial glutamate transporters (GLAST and GLT-1) and a neuronal transporter (EAAC1) in the rat optic nerve. RT-PCR analysis revealed the presence of mRNAs for GLT-1 and GLAST, but not EAAC1. RNase protection assays showed that of the two glial transporters, mRNA for GLAST was expressed at much higher level than was GLT-1. A similar expression pattern was found in primary astrocyte culture cells. GLAST mRNA level in the optic nerve was comparable to that in the cerebellum. Developmentally, GLAST mRNA level was highest at P2 and dropped slightly by adulthood. Nerve transection resulted in little or no change in mRNA levels for GLAST and GLT-1 assayed at 4 to 14 days post-transection, but GLAST mRNA level was decreased at 64 days. Western blot analysis revealed that the rat optic nerve showed immunoreactivity to antibodies against GLT-1, GLAST, and EAAC1. In conclusion, we suggest that glial and neuronal transporters are present in the rat optic nerve, where dynamic axon-glial interaction has been known to occur. In particular, the unusually high level of expression of GLAST in the optic nerve suggests a possible role for this glial transporter in protecting optic nerves from neurotoxicity during postnatal development.     

Release of nociceptin-like substances from the rat spinal cord dorsal horn

Electrophysiological studies have shown that 1-Hz repetitive transcranial magnetic stimulation (rTMS) of the primary motor area (M1) can produce a local decrease in excitability. Functional imaging data suggest that this change may be bilateral. In normal subjects, we measured motor evoked potential (MEP) amplitude at a series of stimulation intensities in the contralateral M1 before and after 15 min of active or sham rTMS at just above the MEP threshold. The slope of the curve relating MEP amplitude and stimulation intensity was decreased in the unstimulated hemisphere by active but not sham rTMS. This demonstrates that rTMS can condition cortical excitability at a distance of one or more synapses and suggest that decreased excitability to TMS is a correlate of decreased blood flow and metabolism.     

Clinical characteristics and natural history of human immunodeficiency virus infected patients seen at a general hospital in Singapore

The number of patients with human immunodeficiency virus (HIV) infection in Singapore has risen over the years. A considerable proportion of them present with acquired immunodeficiency syndrome (AIDS). In this study, we document the clinical characteristics and natural history of a consecutive series of 50 patients who were found to have HIV infection when they were seen at a tertiary care hospital. The majority were in the 30 to 49 age group and the most common mode of acquisition was heterosexual contact. The patients presented with a variety of symptoms to 11 different clinical departments. Fifty-eight per cent of the patients had AIDS-defining illnesses at presentation, with Pneumocystis carinii pneumonia being the most common. On follow-up, the most frequently occurring opportunistic infection that developed was Cytomegalovirus retinitis. Most patients had multiple subsequent admissions--for both AIDS-defining and non AIDS-defining conditions. The median CD4 count of the cohort at presentation was 72/mm3. The median survival was 399 and 822 days in those who had and those who did not have an AIDS-defining illness at presentation, respectively. Mortality was most commonly attributed to pneumonia. HIV infection has protean manifestations and patients may present to various specialty departments; hence, doctors need to be aware of the spectrum of disease in order to make a diagnosis.     

Surgical treatment of pathologic fracture of the femur

A retrospective study of the surgical treatment of 32 metastatic lesions of the femur in 30 patients at the Kaohsiung Medical College Hospital was performed from 1987 to 1994. There were 16 women and 14 men with an average age of 61 years. A surgical technique combining internal fixation or prosthesis and methylmethacrylate cement was used in all cases. Adequate pain relief was achieved in thirty-one cases (97 %). Of the entire group, 20 cases (62%) remained ambulatory, 10 cases (31%) were confined to a wheelchair, only two cases had implant failure and one suffered from infection.     

TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor

We investigated the potential for 9-cis-retinoic acid in the differentiation therapy of neuroblastoma using an N-type neuroblastoma cell line, SH SY 5Y, as an experimental model. In these cells, 9-cis-retinoic acid is more effective than other isomers at inducing the expression of RAR-beta. An RAR-alpha-specific antagonist inhibited the induction of RAR-beta in response to all-trans-but not to 9-cis-retinoic acid. This indicates that the mechanism of gene induction by 9-cis-retinoic acid differs markedly from all-trans-retinoic acid. 9-cis-retinoic acid is also better than all-trans at producing sustained morphological differentiation and inhibition of proliferation of SH SY 5Y cells. Although N-type neuroblastoma cells are not thought to undergo apoptosis in response to all-trans-retinoic acid, we observed a significant degree of apoptosis in SH SY 5Y cells treated with 9-cis-retinoic acid for 5 days and then cultured in the absence of retinoid, an effect not observed in cells treated with the all-trans isomer. These results suggest that 9-cis- and all-trans-retinoic acid have distinct biological properties and that 9-cis retinoic acid may be clinically effective in neuroblastoma by inducing both differentiation and apoptosis under an appropriate treatment regimen.     

Angiotensin-converting enzyme modulates dopamine turnover in the striatum

The effect of chronic inhibition of the angiotensin-converting enzyme on dopamine content and release in the striatum was investigated using in vivo microdialysis in awake, freely moving rats. Rats were treated for 1 week with the angiotensin-converting enzyme inhibitor perindopril (1 mg/kg) via the drinking water, whereas the controls were given water alone. One week after perindopril treatment, striatal dopamine dialysate levels in the treated group were markedly elevated compared with control values: control, 233 +/- 43 pg/ml; perindopril, 635 +/- 53 pg/ml (p < 0.001). These results were confirmed by a complementary study in which dopamine content was measured in striatal extracts (3.5 +/- 0.4 micrograms of dopamine/g of tissue for controls compared with 9.2 +/- 2.4 micrograms of dopamine/g of tissue for the treated group; p < 0.05). In the rats that were dialyzed, angiotensin-converting enzyme levels in the striatum were decreased by 50% after perindopril treatment. Levels of dopamine D1 and D2 receptors and of preprotachykinin and tyrosine hydroxylase mRNAs were unchanged after angiotensin-converting enzyme inhibition. A small, but significant, increase was detected in striatal preproenkephalin mRNA levels in the angiotensin-converting enzyme inhibitor-treated group. These results indicate that peripherally administered angiotensin-converting enzyme inhibitors penetrate the blood-brain barrier when given chronically and modulate extracellular dopamine and striatal neuropeptide levels.     

Enteral feeding intolerance: an indicator of sepsis-associated mortality in burned children

OBJECTIVE: To determine if enteral feeding intolerance (EFI) is associated with sepsis and increased mortality in children with severe burns. DESIGN: A survey. SETTING: A pediatric burn unit. PATIENTS: Ninety-one children surviving longer than 5 days with greater than 80% total body surface area burns. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Enteral feeding intolerance indicated by high gastric residuals (> 150 mL/h) or uncontrollable diarrhea (> 2500 mL/d); thrombocytopenia (platelet count < 100 x 10(9)/L); hyperglycemia (glucose level > 11.1 mmol/L [> 200 mg/dL]); sepsis (pathogenic bacteremia or fungemia noted on blood culture results); and mortality. RESULTS: Neither EFI nor sepsis developed in 71 patients, EFI alone developed in 2 patients, sepsis alone developed in 5 patients, and EFI and sepsis developed in 13 patients. Enteral feeding intolerance and sepsis were associated by contingency table analysis (P<.001). Mortality was 8% (6 patients) in those with neither EFI nor sepsis, 50% (1 patient) in those with EFI alone, 60% (3 patients) in those with sepsis alone, and 77% (10 patients) in those with EFI-associated sepsis. The 2 latter groups were different from the group with neither EFI nor sepsis (P<.05). Enteral feeding intolerance was identified in 70% of patients before sepsis; thrombocytopenia, 64%; and hyperglycemia, 66%. When compared with thrombocytopenia and hyperthermia, no variables were found to be superior to others for predicting sepsis. CONCLUSIONS: Enteral feeding intolerance was associated with the development of sepsis and increased mortality in children with greater than 80% total body surface area burns. This sign was identified in 70% of the cases before pathogens were found in the blood; no difference could be shown between the identification of EFI, thrombocytopenia, and hyperglycemia before sepsis. These data indicate that the development of EFI should be used as an indicator of infection and should prompt a search for an inciting focus.     

Paracrine mechanisms of ovarian follicle apoptosis

Early diagnosis of dementia can be difficult. Quantitative EEG (qEEG) in combination with cognitive tasks shows promise for improving diagnostic accuracy. The study of task induced qEEG changes in normal ageing is a prerequisite for differentiating these changes from those which are specific to dementia. Sixteen young adults (mean age 28.8+/-5.6 years) and 16 healthy cognitively normal older subjects (mean age 73.4+/-7.9 years) participated in the study. EEG recordings were made while subjects were in a relaxed (or resting) state, and also while they performed arithmetic and language tasks. From the resting to the arithmetic conditions, there was decreased alpha activity and increased delta and beta-3 activity for both subject groups. Changes in alpha and delta activity were found in almost all sites and could be associated with arousal. Increase in beta-3 activity was focal, appearing only in the posterior region of the brain and it could be assumed that this area is highly involved in arithmetic processes. In the young adult group, theta activity increased from the resting to the arithmetic conditions, while in the older group theta activity changes were in the opposite direction. From the resting to the language condition, there was increased delta activity and decreased alpha and beta-1 activity for both subject groups. Changes in alpha and delta activity were again found in almost all sites. The decrease in beta-1 activity was found in only four sites, but these were not specific to a region of the brain known to be involved in language processing. This consistency in qEEG changes during cognitive tasks suggests that the method can be applied to the investigation of cognitive deficits associated with a number of neurological syndromes.     

Proton dosimetry in bone using electron spin resonance

We have studied the ESR response of proton-irradiated (in vitro) bone. The ESR response as a function of proton (E = 105 MeV) dose to bone was linear from 0 to 50 Gy and similar to the photon (E = 6 MV) dose response. The ESR depth response (Bragg) curve was depressed as compared to a depth-response curve determined with a parallel plate ionization chamber (PPIC). There was a short-term ESR signal fade in the Bragg peak region, likely attributable to the organic component in bone. We are continuing to investigate these latter two effects.