C-terminal fragment of amyloid precursor protein inhibits calcium uptake into rat brain microsomes by Mg2+-Ca2+ ATPase

Numerous lines of evidence suggest that some of the neurotoxicity associated with Alzheimer's disease (AD) is due to proteolytic fragments of the amyloid precursor protein (APP). Most research has focused on the amyloid beta peptide (A beta). However, the possible role of other cleaved products of APP is less clear. In this study, the effects of a recombinant carboxy terminal 105 amino acid (CT105) fragment of APP on the calcium uptake by endoplasmic reticulum Mg2+-Ca2+ ATPase, the major mechanism for sequestering calcium in this organelle, were investigated. We found that CT 105 is a potent inhibitor of Mg2+-Ca2+ ATPase of endoplasmic reticulum, whereas A beta shows no effect. These results demonstrate that CT 105 inhibits the ability of brain microsomes to sequester calcium and suggest that this inhibitory effect of CT 105 may contribute to disruption of intracellular calcium concentration, possibly being involved in inducing the neural toxicity characteristic of AD.     

Penicillium marneffei fungemia in an AIDS patient: the first case report in Taiwan

The microbiology of in 55 ear aspirates obtained from 34 children with chronic otorrhea was studied. Aspiration of the middle ear exudate was done immediately following removal of tympanostomy tube (TT). The middle ear aspirates and swab specimens of the external auditory canals were cultured for aerobic and anaerobic bacteria. Sixty-five isolates were recovered only from the middle ears, 73 only from the external ear canals, and 73 were present at both sites. Analysis of the 138 middle ear isolates demonstrated the recovery of aerobic bacteria only in 28 patients (50%), anaerobes only in seven (13%), and both aerobes and anaerobes in 20 (36%). There were 77 aerobic and 61 anaerobic isolates. Commonly recovered aerobes were Pseudomonas aeruginosa (17 isolates), Staphylococcus aureus (11), Proteus sp. (7), Moraxella catarrhalis (6), Klebsiella pneumoniae (5) and non-typable Haemophilus influenzae (5). Commonly isolated anaerobes were Peptostreptococcus sp. (25 isolates), Prevotella sp. (10), Bacteroides sp. (8) and Fusobacterium sp. (6). Pseudomonas aeruginosa and S. aureus were more often isolated in children older then 6 years. These findings demonstrate the polymicrobial bacteriology of TT-related otorrhea in children. Specimens collected from the external auditory canals can be misleading. Reliable information can be obtained from the ear exudes when collected through the TT or through the open perforation after their removal.     

Alteration of Kupffer cell function and morphology by low melt point paraffin wax in female Fischer-344 but not Sprague-Dawley rats

This study was conducted to compare the effects of 60-day dietary exposure (2%) to low melt point paraffin wax (LMPW) on both general liver morphology and Kupffer cell (KC) function and morphology in female F-344 and Sprague-Dawley (SD) rats. Livers from only F-344 rats fed LMPW had granuloma formation/lymphoid cell aggregates with small areas of necrosis. Significant increases in serum alanine and aspartate aminotransferase as well as gamma-glutamyltransferase activities were detected only in treated F-344 rats. Additionally, detectable amounts of LMPW were present only in livers of treated F-344 rats. Because KC can be involved in granuloma formation, their morphology and function were examined. Electron microscopy revealed the presence of large, irregularly shaped, membrane-associated vacuoles in cells isolated from F-344 rats exposed to LMPW. These vacuoles were not seen in KC from control rats and rarely detected in KC isolated from LMPW-exposed SD rats. Moreover, indices of KC function including phagocytic activity and nitric oxide and superoxide anion production were significantly increased by KC isolated from F-344 rats exposed to LMPW (1.6-, 36-, and 2.2-fold increases, respectively) over untreated controls. In contrast, LPS-stimulated production of TNF and LTB4 was significantly decreased only in KC of LMPW-fed F-344 rats. No significant changes in these functions were observed in KC isolated from SD rats exposed to LMPW or from KC isolated from control F-344 or SD rats. These data provide evidence that dietary LMPW alters the morphology and functional capacity of KC of F-344 but not SD rats and these changes may ultimately lead to granuloma formation.     

Completion rates and feasibility of outcome measures: experience in a multicenter clinical trial of systemic hypothermia for severe head injury

The National Acute Brain Injury Study: Hypothermia (NABIS:H) is an ongoing multicenter trial of systemic hypothermia for the treatment of severe head injury. Follow-up rates for the study's 3-and 6-month outcome assessments have been maintained at high levels by establishing close contact with family members, by reimbursing cost of travel, and by sending examiners to the subject's location whenever necessary. Two years into the study, global disability data (e.g., Glasgow Outcome Scale) have been obtained on 86% of patients due for 3-month assessment (n = 131) and for all subjects due at 6 months (n = 100). Over half of the patients have completed neuropsychological testing with high reliability ratings. These preliminary findings suggest that the procedures used to document data quality and increase follow-up and completion rates are being successful.     

Long-term neuropsychological outcome and loss of social autonomy after traumatic brain injury

OBJECTIVE: To assess which social activities were still impaired 5 years after a traumatic brain injury (TBI) in adults, and which neuropsychological impairments were associated with this loss of social autonomy. DESIGN: Cross-sectional study of 79 patients selected from the follow-up cohort of an epidemiologic survey of 2,116 TBI patients. SETTING: The present study was of ambulatory patients seen at hospital or at their homes. The inception cohort was from the trauma center of a university hospital and from a general hospital that is representative of level II trauma centers in Aquitaine, France. PATIENTS: Seventy-nine patients selected from a representative sample of 407 patients who were included in the 5-year follow-up study of the initial cohort (convenience sample). MAIN OUTCOME MEASURES: Glasgow Outcome Scale (GOS) and loss of social autonomy as assessed by the European Brain Injury Society's European Head Injury Evaluation Chart; assessment of neurobehavioral impairments by means of the Neurobehavioral Rating Scale-Revised. RESULTS: Up to 16 patients suffered disability for at least one social skill because of cognitive/behavioral reasons. Seven needed full-time supervision. Performing administrative tasks and financial management, writing letters and calculating, driving, planning the week, and using public transport were the most impaired social abilities. Loss of social autonomy was mainly observed in severely injured patients. Univariate analysis showed that mental fatigability, motor slowing, memory difficulties, and disorders of executive function were associated with low scores on the GOS, unemployment, and difficulties in shopping, using public transport, and performing financial management and administrative tasks. CONCLUSION: Persistent impairments of executive functions and speed of psychomotor processing are major factors associated with loss of social autonomy and inability to return to work long after TBI in adults. Improving these impairments in concrete social situations represents a major challenge for cognitive rehabilitation.     

Pediatric meningitis in the Western Cape Province of South Africa

During the 9 years 1985-1993 a prospective survey of all cases of meningitis in children < 13 years of age presenting to our hospital in the Western Cape Province of South Africa was carried out. Two-thousand-nine-hundred-and-twenty cases of meningitis were identified. The commonest form of bacterial meningitis was tuberculous meningitis (TBM) diagnosed in 282 children (mean age 2.94 years). N. meningitidis identified in 220 children (mean age 2.87 years), Haemophilus influenzae in 156 children (mean age 1.15 years) and S. pneumoniae in 106 children (mean age 2.14) were the next commonest causes of bacterial meningitis diagnosed. One-hundred-and-eighteen cases of bacterial meningitis were confirmed in infants < 1 month of age and the commonest bacteria identified were group B beta-haemolytic Streptococcus in 27, E. coli in 21, Klebsiella species in 11, and Candida species in 15 neonates. The emergence of TBM as the predominant cause of bacterial meningitis in childhood at our hospital is probably a reflection of the worsening tuberculosis situation in the Western Cape Province of South Africa.     

Amyloid beta-peptide(25-35) changes [Ca2+] in hippocampal neurons

Insoluble aggregates of the amyloid beta-peptide (A beta) is a major constituent of senile plaques found in brains of Alzheimer disease (AD) patients. The detrimental effects of aggregated A beta is associated with an increased intracellular Ca2+ concentration ([Ca2+]i). We examined the effects of A beta(25-35) on [Ca2+]i and intracellular H+ concentration ([H+]i) in single hippocampal neurons by real time fluorescence imaging using the Ca(2+)- and H(+)-specific ratio dyes, indo-1 and SNARF-1. Incubation of these cultures with A beta(25-35) for 3-12 days in vitro increased [Ca2+]i and [H+]i in large, NMDA-responsive neurons.