Cerebellar atrophy in temporal lobe epilepsy affects procedural memory.

The authors examined a cognitive function mediated by the cerebellum, classical eyeblink conditioning, and its relationship to cerebellar volume in healthy controls (n = 59) and temporal lobe epilepsy subjects (n = 77). Controls demonstrated better conditioning, larger cerebellar volumes, and an association between conditioning and cerebellar volume that was not observed in epilepsy patients. These findings provide support for the hypothesis that cerebellar atrophy in epilepsy affects procedural memory.

Abnormal processing of social information from faces in autism.

Autism has been thought to be characterized, in part, by dysfunction in emotional and social cognition, but the pathology of the underlying processes and their neural substrates remain poorly understood. Several studies have hypothesized that abnormal amygdala function may account for some of the impairments seen in autism, specifically, impaired recognition of socially relevant information from faces. We explored this issue in eight high-functioning subjects with autism in four experiments that assessed recognition of emotional and social information, primarily from faces. All tasks used were identical to those previously used in studies of subjects with bilateral amygdala damage, permitting direct comparisons. All subjects with autism made abnormal social judgments regarding the trustworthiness of faces; however, all were able to make normal social judgments from lexical stimuli, and all had a normal ability to perceptually discriminate the stimuli. Overall, these data from subjects with autism show some parallels to those from neurological subjects with focal amygdala damage. We suggest that amygdala dysfunction in autism might contribute to an impaired ability to link visual perception of socially relevant stimuli with retrieval of social knowledge and with elicitation of social behavior.

Nurse practitioner patient centered telephone calls in a VA primary care geriatric clinic.

PURPOSE: To present original research of a retrospective study of telephone calls by nurse practitioners (NP) to geriatric primary care patients over the period of one year in a Veteran's Administration primary care clinic in the southeast. DATA SOURCES: A convenience sample of the electronic patient progress notes labeled "telephone call" of three full time NPs was collected from May 1, 1998 through April 31, 1999. A total of 1,541 unique telephone calls made by NPs to patients were examined. CONCLUSIONS: Patient telephone calls consume work time, which is often hidden and uncounted when examining time spent with patients. Most calls (62%) were generated by others; the remainder (38%) were initiated by the NPs. The greatest number (42%) of requests related to medication refills. IMPLICATIONS FOR PRACTICE: Many patients requested to talk to the NP for non-clinical issues; many of the requests could have been handled by other staff. It is as if the patient no longer has the traditional call bell to call the nurse but now has the telephone to call the NP. The personal aspect of the phone call may be what is needed by some of the patients looking for a form of human contact.

Cerebellar functional abnormalities in schizophrenia are suggested by classical eyeblink conditioning.

BACKGROUND: Previous research suggests that schizophrenia may result from disruptions in a cortico-cerebellar-thalamic-cortical circuit (CCTCC) producing a mental incoordination or "cognitive dysmetria." To further evaluate the cerebellar contribution to this disrupted circuitry, medication-free patients with schizophrenia completed classical eyeblink conditioning, a cerebellar-mediated learning task. METHODS: For classical eyeblink conditioning, 70 trials with a tone conditioned stimulus (CS) and air puff unconditioned stimulus (US) were presented to 15 patients with schizophrenia and 15 healthy control subjects. Acquisition rate for the conditioned response (CR) and response timing were compared between the two groups. RESULTS: Patients with schizophrenia displayed facilitated conditioning compared to control subjects based on a greater number of CRs during the session and a faster acquisition of the learned response. CONCLUSIONS: Facilitated conditioning suggests that an enhanced excitability in the cerebellum occurs as part of a disrupted CCTCC in schizophrenia. The enhanced cerebellar-mediated associative learning may be maladaptive in the context of normal cerebro-cerebellar interactions, leading to the characteristic motor and mental incoordination of the disorder. Classical eyeblink conditioning may provide a useful model system for studying cerebellar involvement in the pathogenesis and treatment of schizophrenia.

An MRI study of the basal ganglia in autism.

1. High-resolution MRI scans were obtained from 35 relatively high-functioning persons with autism and 36 healthy controls, comparable in age, gender, and IQ. 2. Volumetric measurements were obtained from manual tracing of the bilateral caudate, putamen, and globus pallidus. 3. An increased volume of the caudate nuclei was found in subjects with autism. Caudate enlargement was proportional to increased total brain volume in subjects with autism. 4. Caudate volume was associated with compulsions and rituals, difficulties with minor change, and complex motor mannerisms in autism. 5. Based on evidence of caudate abnormalities, a second MRI study was completed which replicated the finding of caudate enlargement in autism using an independent sample. 6. The caudate may be part of an abnormal distributed neural network in autism and involved in the ritualistic--repetitive behaviors of the disorder.

The effect of administering long-acting oxytetracycline and tilmicosin either by dart gun or by hand on injection site lesions and drug residues in beef cattle.

Forty yearling cattle were injected intramuscularly with long-acting oxytetracycline and subcutaneously with tilmicosin by dart gun or by hand in a chute 28 days prior to slaughter. The drugs caused injection site lesions and antibiotic residues in the neck and thigh that varied by technique, dose, and site.

Effects of haloperidol on sensory processing in the hippocampus during classical eyeblink conditioning.

The rabbit classical eyeblink conditioning paradigm was used to assess the effects of haloperidol on hippocampal function. Haloperidol disrupted hippocampal activity and conditioned responses (CRs) at low but not high conditioned stimulus (CS) intensities. The observed relationship of hippocampal activity and the CR suggested that the hippocampus encoded sensory features associated with the learned response. Sensory processing by the hippocampus appeared to be altered by haloperidol through attenuation of the ability of a CS to evoke a learned response. Results are discussed in terms of the role of the hippocampus in sensory processing and possible mechanisms for the beneficial effects of haloperidol in schizophrenia. Classical eyeblink conditioning may provide a model system for studying behavioral and biological issues relevant to the etiology and treatment of schizophrenia.

Case study: cross-gender preoccupations with two male children with autism.

Persons with autism frequently exhibit circumscribed interests and unusual preoccupations. In this case study, two young males with autism are presented who have preoccupations with feminine gender-stereotyped activities and objects. These types of preoccupations in children with autism have not been reported in the literature, but may be more prevalent than realized due to parental underreporting given the negative stigma associated with feminine interests in young boys. The development of gender identity in young children with autism has rarely been addressed in the literature. It seems unlikely that these two cases can be categorized as gender identity disorders. Understanding these preoccupations in the context of autism rather than focusing on the gender identity issues has important implications for treatment. These cases point to the need for further study of the complex interplay of environmental and neurobiologic factors affecting gender identity roles and preoccupations in autism.

BaeI, another unusual BcgI-like restriction endonuclease.

BcgI and BcgI-like restriction endonucleases have a very distinct characteristic which causes them to differ from the other classified restriction enzymes; they all cleave double-stranded DNA specifically on both sides of the recognition sequence to excise a short DNA fragment including the recognition sites. Here we report a new BcgI-like restriction endonuclease, BaeI, isolated from Bacillus sphaericus. Like BcgI, BaeI also cleaves double-stranded DNA on both strands upstream and downstream of its recognition sequence (10/15)ACNNNNGTAYC(12/7). There are two dominant polypeptides in the final preparation of BaeI with molecular masses of approximately 80 and 55 kDa. Both are slightly larger than the two BcgI subunits. BaeI requires both Mg2+ and AdoMet to cleave DNA. Accompanying bilateral cleavage activity, the heteromeric BaeI also has an N6-adenine methyltransferase activity which modifies the symmetrically located adenines within its recognition sequence.

Involvement of the ventrolateral thalamic nucleus in rabbit classical eyeblink conditioning.

The involvement of the ventrolateral nucleus of the thalamus in relaying learning-related activity to higher brain structures during classical conditioning of the rabbit eyelid response was examined in two experiments. In the first study, multiple-unit ventrolateral thalamic nucleus activity was monitored before and after lesions of either the cerebellar interpositus nucleus or red nucleus were given. Before the lesions were given, conditioned response-related activity was observed in the ventrolateral thalamic nucleus. Lesions of the interpositus nucleus, but not the red nucleus, disrupted the conditioning-related activity in the ventrolateral thalamic nucleus, thus suggesting that an efferent copy of conditioned response-related activity is projected directly from the interpositus nucleus to higher brain areas by way of the ventrolateral thalamic nucleus. In the second study, multiple unit activity in the hippocampus was monitored before and after lesions were placed in the ventrolateral thalamic nucleus or red nucleus. Conditioning-related activity in the hippocampus was not affected by either lesion, thus suggesting that maintenance of training-related activity in the hippocampus is not critically dependent on cerebellar information relayed through the ventrolateral thalamic nucleus or red nucleus.

Abnormal classical eye-blink conditioning in autism.

Cerebellar and limbic system pathologies have been reported in persons with autism. Because these brain areas are involved centrally in the acquisition and performance in classical eye-blink conditioning, this study evaluated conditioning in 11 persons with autism. Compared to matched controls, persons with autism learned the task faster but performed short-latency, high-amplitude conditioned responses. In addition, differences in learning the extinction rates systematically varied with age thus suggesting a developmental conditioning abnormality in autism. The observed pattern of eye-blink conditioning may indicate that persons with autism have the ability to rapidly associate paired stimuli but, depending on processing of certain contextual information, have impairments in modulating the timing and topography of the learned responses. This abnormality may relate to deviant cerebellar-hippocampal interactions. The classical eye-blink conditioning paradigm may provide a useful model for understanding the biological and behavioral bases of autism.

Possible CS and US pathways for rabbit classical eyelid conditioning: electrophysiological evidence for projections from the pontine nuclei and inferior olive to cerebellar cortex and nuclei.

Projections from the lateral region of the pontine nuclei and the dorsal accessory inferior olive to both cerebellar cortex and cerebellar dentate/interpositus nuclei were electrophysiologically examined using single-pulse stimulation and single-unit and population recording. Stimulation of the pontine nuclear region activated population potentials and single units recorded in both cerebellar cortex and deep nuclei. Pontine-evoked activity in cerebellar cortex (Larsell's lobule HVI and adjacent areas) was rather well-defined and strong while pontine-evoked activity in the deep cerebellar nuclei seemed relatively more diffuse and weaker. Short onset latencies for both single units and population potentials were found suggesting direct projections. Similar to previous studies, inferior olive stimulation evoked short-latency responses in cerebellar cortex and nuclei thus suggesting direct projections. More pontine- and olivary-evoked activity was seen in cortex than in the nuclei with slightly more olivary-evoked potentials per recording electrode penetration observed than pontine-evoked activity. Our findings suggest that cortical and nuclear regions of the cerebellum receive converging projections from the pontine nuclei and inferior olive, projections that may carry information about stimuli used during classical conditioning. These findings are discussed in terms of cerebellar circuits that may be involved in classical eyelid conditioning.

CircumVent thermal cycle sequencing and alternative manual and automated DNA sequencing protocols using the highly thermostable VentR (exo-) DNA polymerase.

CircumVent thermal cycle and standard DNA sequencing protocols utilizing the cloned and highly thermostable VentR (exo-) DNA polymerase are described. The thermal cycle sequencing procedures are advantageous because they allow fast and simple semiautomation of the sequencing reaction; make possible the direct DNA sequencing of PCR products, bacterial colonies and phage plaques; require only femtomoles of template DNA; eliminate the requirement of an independent primer annealing step; remove the requirement of denatured plasmids for sequencing double-stranded templates; and use a highly thermostable DNA polymerase for sequencing through potential recalcitrant secondary structure domains and large linear double-stranded DNA templates such as lambda derivatives. More standard methods of DNA sequencing (i.e., a one-step protocol and a labeling-termination protocol) are also presented. For each protocol, alternatives for choice of label and method of labeling are presented, including the use of 5' biotinylated primers for chemiluminescent DNA sequencing and fluorinated primers for automated sequencing using the BaseStation Automated DNA Sequencer.

Mutagenesis of ribosomal protein S8 from Escherichia coli: defects in regulation of the spc operon.

The structural features of Escherichia coli ribosomal protein S8 that are involved in translational regulation of spc operon expression and, therefore, in its interaction with RNA have been investigated by use of a genetic approach. The rpsH gene, which encodes protein S8, was first inserted into an expression vector under the control of the lac promoter and subsequently mutagenized with methoxylamine or nitrous acid. A screening procedure based on the regulatory role of S8 was used to identify mutants that were potentially defective in their ability to associate with spc operon mRNA and, by inference, 16S mRNA. In this way, we isolated 39 variants of the S8 gene containing alterations at 34 different sites, including 37 that led to single amino acid substitutions and 2 that generated premature termination codons. As the mutations were distributed throughout the polypeptide chain, our results indicate that amino acid residues important for the structural integrity of the RNA-binding domain are not localized to a single segment. Nonetheless, the majority were located within three short sequences at the N terminus, middle, and C terminus that are phylogenetically conserved among all known eubacterial and chloroplast versions of this protein. We conclude that these sites encompass the main structural determinants required for the interaction of protein S8 with RNA.

Cerebellar interpositus nucleus lesions disrupt classical nictitating membrane conditioning but not discriminative avoidance learning in rabbits.

Cerebellar interpositus nucleus lesions were given to 14 rabbits trained in two behavioral paradigms; discriminative avoidance conditioning of locomotor behavior and classical nictitating membrane conditioning. Bilateral lesions that prevented acquisition of the classically conditioned response on both the left and right side failed to affect the acquisition or performance of the conditioned discriminative avoidance response. The results are discussed in terms of differences in neural substrates that apparently subserve the two forms of learning.

Application of a novel chemiluminescence-based DNA detection method to single-vector and multiplex DNA sequencing.

A chemiluminescent DNA detection method is described and its application shown for both single-vector and multiplex DNA sequencing using the standard dideoxy chain-termination process. This recently developed detection method, which utilizes the light emitted by an enzyme-catalyzed dioxetane reaction, is highly sensitive and affords significant advantages in safety and speed over the traditional radioactive labeling method. When adapted to a multiplex strategy, this chemiluminescent detection method constitutes a safe, simple and rapid method for increasing the throughput of DNA sequencing procedures.

Dorsal accessory inferior olive activity diminishes during acquisition of the rabbit classically conditioned eyelid response.

Eight rabbits were implanted with chronic recording electrodes in the rostromedial region of the dorsal accessory inferior olive (DAO). Multiple-unit DAO activity was recorded during 5 training sessions consisting of paired tone conditioned stimulus (CS) and air puff unconditioned stimulus (US) trials. Initially, the air puff US produced a large somatosensory-evoked response in the DAO during the paired CS-US presentations. As percent CRs increased across sessions, however, the DAO activity on paired trials decreased dramatically. In contrast, there were no significant decreases in DAO activity on US-alone trials presented at the end of each paired conditioning session. These results suggest that an associative process suppresses DAO activity during classical eyelid conditioning. Possible mechanisms of DAO inhibition and its involvement as part of the US 'reinforcement' pathway are discussed.