Sustained activation of the hippocampus in response to fearful faces in schizophrenia.

BACKGROUND: In healthy individuals, the activity of the medial temporal lobe habituates rapidly with the repeated presentation of a stimulus. Using functional magnetic resonance imaging (fMRI), we tested the hypothesis that habituation of the medial temporal lobe is reduced in schizophrenia. METHODS: During fMRI scanning, fearful and happy faces were presented repeatedly to healthy control subjects (n =16) and patients with schizophrenia (n =18). Habituation of medial temporal lobe structures was measured by comparing the hemodynamic response occurring during the early and late portions of the presentation of each face. RESULTS: Control subjects demonstrated significant medial temporal lobe habituation to fearful but not to happy faces. In contrast, patients with schizophrenia did not demonstrate medial temporal lobe habituation in response to fearful or happy faces. In a direct, between-group comparison, right hippocampal habituation to fearful faces was significantly greater in control subjects than in the schizophrenia patients. Also, there were no significant differences between the patients and control subjects in the early medial temporal lobe response to fearful faces, suggesting that attenuated hippocampal habituation in schizophrenia is not associated with a reduction in initial activation. CONCLUSIONS: These findings suggest that there is abnormal modulation of hippocampal responses to fearful faces in schizophrenia.     

Polymerase chain reaction haplotyping using 3' mismatches in the forward and reverse primers: application to the biallelic polymorphisms of tumor necrosis factor and lymphotoxin α

A polymerase chain reaction with sequence-specific primers (PCR-SSP) system that operates under identical conditions to HLA phototyping was devised for characterizing polymorphisms in tumor necrosis factor (TNF) and lymphotoxin α (LT-α). Mismatches at the 3' end were incorporated into the forward and reverse primers of each PCR so as to unequivocally establish the cis / trans status between the biallelic sites. Three previously described biallelic polymorphisms in TNF and three in LT-α were characterized in a 24-reaction PCR-SSP system. The method was used to genotype 20 cell lines and 201 HLA class I and II typed controls from the United Kingdom at the TNF and LT-α loci. Population frequencies of TNF haplotypes were determined as was linkage disequilibrium with HLA-A, B, Cw, DRB1 and DQB1 loci. In each gene there were 8 theoretical polymorphic combinations; 4 were observed in TNF and 4 in LT-α. A total of 11 TNF-LT-α haplotypes were determined from apparent homozygous controls and statistical analysis.     

Lack of high affinity fiber receptor activity explains the resistance of ciliated airway epithelia to adenovirus infection.

Although recombinant adenoviruses are attractive vectors for gene transfer to airway epithelia, they have proven to be relatively inefficient. To investigate the mechanisms of adenovirus-mediated gene transfer to airway epithelia, we examined the role of adenovirus fiber and penton base, the two proteins involved in attachment to and entry of virus into the cell. We used human airway epithelia grown under conditions that allow differentiation and development of a ciliated apical surface that closely resembles the in vivo condition. We found that addition of fiber protein inhibited virus binding and vector-mediated gene transfer to immature airway epithelia, as well as to primary cultures of rat hepatocytes and HeLa cells. However, fiber protein had no effect on vector binding and gene transfer to ciliated airway epithelia. We obtained similar results with addition of penton base protein: the protein inhibited gene transfer to immature epithelia, whereas there was no effect with ciliated epithelia. Moreover, infection was not attenuated with an adenovirus containing a mutation in penton base that prevents the interaction with cell surface integrins. These data suggest that the receptors required for efficient infection by adenovirus are either not present or not available on the apical surface of ciliated human airway epithelia. The results explain the reason for inefficient gene transfer and suggest approaches for improvement.     

Activation of normal and cystic fibrosis Cl- channels by voltage, temperature, and trypsin.

In cystic fibrosis (CF) phosphorylation-dependent activation of outwardly rectifying apical membrane Cl- channels is defective. To further understand regulation of this channel we examined several other mechanisms of channel activation in normal and CF cells. Previous studies have shown that strong membrane depolarization can activate channels in excised cell-free membrane patches. Here we show that such activation is dependent on both the absolute membrane voltage and the duration of depolarization. Moreover, activation was reversible by membrane hyperpolarization. In some cases, excising patches of membrane from the cell caused channel activation, even in the absence of depolarization. However, the frequency of channel activation with patch excision increased when bath temperature was increased from 23 to 37 degrees C. Although the channel remained in the activated state when temperature was reduced to 23 degrees C, subsequent hyperpolarization inactivated the channel. In cell-attached patches, neither depolarization nor increasing bath temperature to 37 degrees C activated channels, suggesting that neither is physiologically important in regulation of the channel. Thus changes in membrane voltage and bath temperature appear to cause a nonenzymatic change in the channel's conformation; the interactions between voltage and temperature suggest that they may affect the same process. To determine if a proteolytic alteration of the channel could also cause activation, we added trypsin to the cytosolic surface of excised membrane patches. Trypsin activated channels, which could not then be inactivated by either hyperpolarization or phosphorylation with PKC, suggesting that trypsin removed or altered a region of the channel involved in inactivation. All of these interventions activated Cl- channels from both normal and CF cells. Thus many aspects of Cl- channel activation are normal in CF; only phosphorylation-dependent activation is defective.     

Characteristics of a cetacean morbillivirus isolated from a porpoise (Phocoena phocoena)

Summary A virus isolated from a porpoise during the 1988 seal epizootic was shown to be a morbillivirus. In order to determine the relationship of the virus to phocine distemper virus (PDV) a battery of monoclonal antibodies raised against canine distemper virus (CDV), PDV or the porpoise isolate were assessed for their ability to bind to CDV, PDV or porpoise virus epitopes in indirect immunofluorescence assays and ELISAs. The porpoise isolate contained several unique epitopes and several epitopes present on CDV and PDV were absent on the porpoise isolate. The data presented in this study indicate that the porpoise virus is an antigenically distinct morbillivirus and as such has been tentatively named as delphinoid distemper virus (DDV).     

Spontaneous rupture of the quadriceps tendon and patellar ligament during treatment for chronic renal failure.

The quadriceps tendon and patellar ligament rupture rarely, even when under great stress or trauma, but can rupture spontaneously in patients with chronic diseases such as gout, rheumatoid arthritis and renal disease. Several factors probably combine to weaken the tendon, including an impoverished local vascular supply, repeated microtrauma and secondary hypoparathyroidism with osteodystrophy. In the three cases reported here, one of which was bilateral, the patients were being treated for chronic renal disease; surgical repair of the tendons led to sound healing and a return to normal function of the joints.