A novel mutation of presenilin 1 in familial Alzheimer's disease in Israel detected by denaturing gradient gel electrophoresis

Germline mutations in the presenilin 1 (PS1) gene apparently account for the majority of early-onset, familial Alzheimer's disease (AD). Using a mutation-screening strategy (denaturing gradient gel electrophoresis; DGGE), we analyzed a large family with early onset AD and seizures. The patients in this family showed a novel missense mutation in exon 5 of the PS1 gene (A to T change in codon 120, altering glutamine to aspartic acid). This novel mutation is located within the second hydrophilic domain of the molecule, a region not particularly involved in previously described germline mutations, and is of unknown biological significance. These results also demonstrate that DGGE can be used effectively to screen for mutations within this gene.     

A stingray spine in the scapula of a bottlenose dolphin

A stingray spine was found lodged in the scapula of a deceased 272 cm, male bottlenose dolphin (Tursiops truncatus) from South Carolina (USA) following skeletal preparation, nearly 6 mo after necropsy. No external puncture wound, internal bruising, or laceration of muscle tissue surrounding the scapula was evident during necropsy of the animal. Implantation of the spine did not appear to be related to the death of the dolphin, but probably occurred at an early age. Abnormal development of bone surrounding the spine resulted in the formation of a cavity at the wound site. Two mechanisms were considered as contributors for the cavity formation. These were the mechanical action of the spine stimulating the body's defense system for managing foreign objects, and the release of potent toxins from the spine sheath.     

Zoonotic Brugian lymphadenitis. An unusual case with florid monocytoid B-cell proliferation

Human infection with a zoonotic Brugia species in the United States is uncommon. Positive identification of the filarial nematode is required for histopathologic diagnosis. Many cases may go unrecognized because of the nonspecific clinical manifestations and the nondiagnostic histologic changes occurring in involved lymph nodes. A case of zoonotic Brugia lymphadenitis is described in a patient from Rhode Island, in which a small nongravid female worm was identified in a lymph node biopsy specimen. The lymph node also showed a spectrum of reaction changes including the presence of florid monocytoid B-cell proliferation, which has not been described in association with zoonotic Brugian filariasis.     

Management of lymphoproliferative disorders after cardiac transplantation

We conducted a retrospective study of 516 cardiac recipients who underwent transplantation between April 1983 and April 1992, 19 of whom had development of post-transplantation lymphoproliferative disorders (PTLDs). These 19 patients presented with involvement of lung (5), gastrointestinal tract (5), disseminated disease (6), and adenoids and lymph nodes (3). B-cell proliferations ranging from an atypical hyperplasia to malignant lymphoma developed in 18 patients, and mixed cellularity Hodgkin's disease developed in 1 patient. The 19 patients with PTLD displayed a predominance of both women and cardiomyopathy as the indication for transplantation when compared with two separate control populations. No correlation was found between demographic criteria analyzed and (1) early versus late diagnosis of PTLD after transplantation, (2) the site of PTLD involvement, or (3) the histopathologic category of the PTLD lesion. Patients with gastrointestinal tract and lung PTLD involvement enjoyed an improved survival after both transplantation and PTLD diagnosis when compared with patients with PTLD involvement of all other extranodal sites. We report a high incidence of PTLD involving the lung and gastrointestinal tract in our cohort study. These sites of involvement responded better to a reduction in immunosuppression than did the other extranodal sites of involvement.     

Cortical cholinergic impairment and behavioral deficits produced by kainic acid lesions of rat magnocellular basal forebrain.

The rat magnocellular basal forebrain (MNBF) is homologous to the human nucleus basalis of Meynert, a structure implicated in the cholinergic hypothesis of cognitive impairment in Alzheimer's disease (AD). In the present study, 18 male Sprague-Dawley rats with kainic acid lesions in the MNBF were compared with 6 unoperated controls, 10 sham-operated controls, and 6 controls injected with kainic acid in the cortical area directly above the MNBF. MNBF lesions depleted choline acetyltransferase in cortex but not in striatum or hippocampus. Cortical dopamine levels were unchanged; serotonin levels were unchanged in hippocampus and parietal cortex but decreased in frontal cortex. Compared with controls, MNBF-lesioned Ss were impaired in 24-hr retention, but not acquisition, of a passive avoidance task with escapable footshock. The groups did not differ in mean number of daily avoidances on a barpress active avoidance task, although learning was slower in MNBF-lesioned Ss. In a serial spatial discrimination reversal test, MNBF-lesioned Ss performed significantly worse than controls. This model may be useful for studying the role of the cholinergic system in memory and possibly for developing treatment strategies to alleviate the cognitive dysfunction of AD. (63 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prevalence of serologic markers of HBV, HDV, HCV and HIV in non-injection drug users compared to injection drug users in Gran Canaria, Spain

Von Hippel-Lindau disease (VHL) is an autosomal dominant tumour syndrome caused by germline mutations of the VHL tumour suppressor gene located on chromosome 3p25-26. In VHL tumours may occur in 14 different target organs, including the eye. Retinal angiomas are considered the first manifestation of VHL disease in 43% of cases, and the cumulative probability of developing a retinal angioma in one or both eyes rises during each decade of life, reaching 80% for patients over 80 years old. Since 1976 patients with VHL at the University Hospital of Utrecht and their at-risk relatives have been screened periodically by a multidisciplinary team. Long-term follow-up ophthalmological data were analysed with special attention to natural course and results of treatment. In addition, we looked for a genotype-phenotype correlation. Retinal angiomas were found in all families. In one large family with a missense mutation (V170D) of the VHL gene, in which the complete spectrum of visceral- and central nervous system (CNS) features of VHL is present, macular, parapapillary, optic disc and ora serrata angiomas were also found. In general, however, a clear-cut genotype-phenotype correlation could not be found. Only early detection and treatment of peripheral retinal angiomas can be expected to decrease the percentage of patients with decreased visual acuity. Therefore, early detection and treatment of these tumours is of paramount importance. Ophthalmological screening of patients and persons at risk should start as early as possible. In patients with apparently sporadic retinal angiomas it is advisable to perform germline DNA analysis, since the risk of developing VHL is high, especially if the angiomas are bilateral, or unilateral and multifocal, if the patient is young, or if there is a family history suggestive of VHL.     

alpha B-crystallin and hsp25 in neonatal cardiac cells--differences in cellular localization under stress conditions

OBJECTIVES: The aim of this study was to determine (a) whether delay in femur fracture stabilization beyond twenty-four hours in patients with head injury increased the risk of pulmonary complications and (b) whether immediate (up to twenty-four hours) femur fracture stabilization increased the risk of central nervous system (CNS) complications. DESIGN: Retrospective analysis. MATERIALS AND METHODS: Thirty-two patients with femur fracture and head injury were identified. Fourteen underwent immediate stabilization of their fractures, and eighteen underwent delayed (four-teen patients) or no (four patients) stabilization of their fractures. RESULTS: In the immediate stabilization group, five patients had severe head injuries [Glasgow Coma Score (GCS) < or = 8] and nine had mild head injuries (GCS > 8). In the mild head injury group, no patient had a pulmonary complication and one had a CNS complication. In the severely head-injured group, one patient had a pulmonary complication and no patient had a CNS complication. In the delayed stabilization group, six patients had mild head injuries (GCS > 8) and twelve had severe head injuries (GCS < or = 8). In the mildly head injured group, one patient had a pulmonary complication, two patients had CNS complications, and one patient died. In the severely head injured group, nine patients had pulmonary complications, three patients had CNS complications, and one patient died. Logistic regression identified delay in femur stabilization as the strongest predictor of pulmonary complication (p = 0.0042), followed by severity of chest Abbreviated Injury Score (AIS; p = 0.0057) and head AIS (p = 0.0133). Delaying fracture stabilization made pulmonary complications forty-five times more likely. Each point increase in the chest AIS and head/neck AIS increased the risk of pulmonary complication by 300 percent and 500 percent, respectively. A statistically significant predictor of CNS complications could not be identified by using logistic regression. CONCLUSION: Delay in stabilization of femur fracture in head-injured patients appears to increase the risk of pulmonary complications. However, due to selection bias in this patient sample, this question cannot be definitively answered. Early fracture stabilization did not increase the prevalence of CNS complications.     

Effects of corticotropin-releasing factor on brain serotonergic activity

The serotonergic dorsal raphe nucleus is innervated by corticotropin-releasing factor (CRF) and expresses CRF receptors, suggesting that endogenous CRF impacts on this system. The present study characterized interactions between CRF and the dorsal raphe serotonin (5-HT) system. The effects of intracerebroventricularly (i.c.v.) administered CRF on microdialysate concentrations of 5-HT in the lateral striatum of freely moving rats were determined. CRF had biphasic effects, with 0.1 and 0.3 microgram decreasing, and 3.0 micrograms increasing 5-HT dialysate concentrations. i.c.v. administration of CRF inhibited neuronal activity of the majority of dorsal raphe neurons at both low (0.3 microgram) and high (3 micrograms) doses. Likewise, intraraphe administration of CRF (0.3 and 1.0 ng) had predominantly inhibitory effects on discharge rate. Together, these results suggest that CRF is positioned to regulate the function of the dorsal raphe serotonergic system via actions within the cell body region. This regulation may play a role in stress-related psychiatric disorders in which 5-HT has been implicated.