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The promoter of the latency-associated transcripts of herpes simplex virus type 1 contains a functional cAMP-response element: role of the latency-associated transcripts and cAMP in reactivation of viral latency.

A 203-base-pair sequence 5' of the latency-associated transcripts (LATs) of herpes simplex virus type 1 contains a 7-base consensus sequence TGCGTCA that is identical to the cAMP-response element of the proenkephalin gene. This consensus sequence is at -38 relative to the putative 5' end of the LATs with a TATA box at the -24 position. In transient chloramphenicol acetyltransferase assays in rat pheochromocytoma (PC12) cells, this enhancer region stimulated gene expression up to 3-fold in the presence of dibutyryl cAMP, forskolin, nerve growth factor, or phorbol 12-myristate 13-acetate. Mutation of the cAMP-response element to TGCG-CAA resulted in a 4-fold reduction of basal activity and a complete loss of inducible stimulation. In DNA gel retardation assays, purified cAMP-response element-binding protein and a nuclear protein from PC12 cells were shown to bind specifically to this element. Furthermore, it was demonstrated that the reactivation of wild-type herpes simplex virus type 1 from dissociated latently infected murine trigeminal ganglia was significantly accelerated (P less than 0.005) by the addition of cAMP analogs or adenylate cyclase activators. However, these reagents did not accelerate reactivation of a deletion mutant that lacks the putative cAMP-response element-containing promoter region, transcriptional start site, and 1015 base pairs of the LATs. These studies demonstrate that the promoter region of the LATs contains a functional cAMP-response element and that expression of the LATs is likely controlled by second messenger signal transduction and imply a role for cAMP in triggering viral reactivation.

Animals

Internight variability of REM latency in major depression: implications for the use of REM latency as a biological correlate.

The internight variability in REM latency in 92 drug-free inpatients with major depressive illness was recorded for 4 consecutive nights and subsequently assessed. Individual coefficients of variation in REM latency [CV = (standard deviation of mean REM latency for 4 recording nights/4-night mean REM latency) X 100] ranged from 5.1 to 121.7, with a mean of 37.0 (SD = 27.3) and a median of 27.4. CV was positively correlated with both age (p less than 0.05) and age at onset of depressive illness (p less than 0.01). Male patients showed more variability in REM latency than female patients (p less than 0.05); likewise, the subgroups of patients who either were incapacitated or had bipolar II illness showed greater variability in REM latency in comparison with the remainder of the sample (p less than 0.05). When the entire patient sample was stratified by CV into three equal subgroups, the subgroup of patients defined by the highest CV presented the longest sleep latency (p less than 0.05) and the shortest REM latency (p less than 0.0001). No other clinical or polysomnographic correlates of REM latency variability were noted nor was REM latency variability related to severity of illness, other subtypes of illness, or clinical response to antidepressant therapy. In selecting REM latency data for assessment of diagnostic sensitivity, the use of the shortest REM latency from at least 3 consecutive nights yielded a higher sensitivity (74%-81%) than did the use of any one individually specified night (50%-56%) or different internight means (49%-52%). The same conclusion applied when patient age was taken into account. These results have implications for standardizing the use of REM latency as a biological correlate in major depression.

Adult

[The severity of dementia and brainstem auditory evoked potentials--peak latency and interpeak latency].

We have examined the correlation of dementia severity and brainstem auditory evoked potentials. The subjects were 80 patients with dementia (20 males, 60 females) whose mean age was 80.7 years. Normal controls were 9 elderly subjects (2 males, 7 females) whose mean age was 80.4 years. The following parameters were measured: peak latencies (I, III and V), interpeak latencies (I-III, III-V and I-V) and interaural latency differences (V PLDs and I-V IPLDs). As for clinical items and sex differences; (1) There were sex differences recognized between peak latency of III and V, interpeak latency of III-V and I-V. (2) There was a significant difference in interaural differences of V PL Ds between vascular dementia and degenerative dementia (dementia of the Alzheimer's type and Parkinson's disease). Duration of illness had no correlation with latencies of BAEPs. Dividing the patients into three groups according to the severity of dementia which are mild, moderate and severe, (3) peak latency of III, V and interpeak latency of I-III, III-V, I-V and interaural latency differences of V PL Ds prolonged significantly with the increasing severity of dementia. From these results, it is suggested that brainstem dysfunction progresses with the increasing severity of the dementia.

Aged

The cause of increased pupillary light reflex latencies in diabetic patients: the relationship between pupillary light reflex and visual evoked potential latencies.

In 42 diabetic patients the relationship between the latency of the pupillary light reflex and the pattern reversal visual evoked potential (P100) was examined. Fifty-five percent of diabetic patients had pupillary light reflex latencies above the normal range. In 19% the visual evoked potentials were prolonged when compared to the normal range. Latencies of pupillary light reflexes and VEPs showed no correlation. There was a minimal correlation between the presence of retinopathy and prolongation of both the pupillary light reflex and the visual evoked response latency (kappa coefficients respectively: 0.31, P less than 0.01 and 0.36, P less than 0.02). The presence of an increased pupillary light reflex latency was positively correlated with a reduced respiratory sinus arrhythmia (kappa coefficient: 0.58, P less than 0.0001). Increased VEP latencies showed no correlation with signs of cardiovascular autonomic neuropathy. We conclude that the afferent optic pathway can be affected in diabetic patients. However, prolongation of pupillary light reflex latency in diabetic patients is primarily due to an efferent pupillary defect and represents parasympathetic dysfunction.

Adult

Xenopus exhibits seasonal variation in retinotectal latency but not tecto-isthmo-tectal latency.

1. The tectum of Xenopus receives visuotopic input from both eyes. The contralateral eye's projection reaches the tectum directly, via the optic nerve. The ipsilateral eye's projection reaches the tectum indirectly, via the nucleus isthmi and isthmo-tectal projection. 2. Because of the multi-synaptic nature of the ipsilateral pathway, there is an inherent delay between the time that information from the contralateral eye reaches the tectum and the time that information from the ipsilateral eye arrives at the tectum. The length of the intertectal delay is a function of the latencies of the contralateral and ipsilateral pathways. 3. The length of this intertectal delay has functional, as well as developmental, implications with regard to the role of N-methyl-D-aspartate receptors in tectal cell activity and development of orderly synaptic connections. 4. We have found that the latencies of the contralateral and ipsilateral pathways exhibit a seasonal variation, increasing during the winter months. The increases of both latencies during the winter were of similar magnitude, indicating that there were no significant changes in intertectal delay. The seasonal alteration in contralateral latency was not affected by dark-rearing and was affected to only a minor extent by a week-long alteration of ambient temperature.

Animals

H reflex latency as an adequate predictor of the spinal evoked potential latency.

By stimulation of the posterior tibial nerve, somatosensory responses can be recorded at the level of the popliteal fossa, thoraco-lumbar spinal region and scalp. The thoraco-lumbar spinal potential is frequently difficult to record. Therefore several methods to estimate its latency were used and the results were compared with the real latency of the N24 recorded at spinal level in a group of healthy volunteers. A formula using the Hoffmann reflex latency (H-M interval) proved to be the most adequate for this purpose. By knowing the spinal potential latency, either through direct recording or through estimation by the formula, determination of a central conduction time, the N24-P40 interval, is possible. Normative values for this parameter are given.

Adult

Behavioral and neural characteristics of short-latency and long-latency conditioned responses in cats.

Head movements to the conditioned stimulus (a tone CS to the left ear) were studied in 6 cats. An attempt was made to differentiate an orienting, short-latency (alpha) response from the long-latency conditioned (delayed) response. The unconditioned stimulus (UCS) was a brain stimulation to the lateral hypothalamus eliciting, in addition to orienting and approach behavior, a specific, stereotypical head movement. These behavioral characteristics of the unconditioned head movement were used for differentiating it from the conditioned short-latency head movement. Paired conditioning and randomly unpaired control sessions (5 daily sessions each) were given in balanced order to each animal. Evoked neural responses in the hippocampus and cingulate cortex were recorded simultaneously to compare the time-amplitude characteristics of evoked responses to earlier findings in multiple-unit recordings. The results supported the differentiation of the behavioral responses. The time-amplitude course of the evoked neural responses showed complex changes, appearing as an increase in the negativity during the alpha-response period (150- to 450-ms interstimulus interval [ISI]) and as an increase in the positivity during the long-latency period (700- to 1,000-ms ISI + 150- to 450-ms UCS period) on omitted-UCS (CS-alone test) trials.

Alpha Rhythm

Herpes simplex virus type 1 latency-associated transcription unit promotes anatomical site-dependent establishment and reactivation from latency.

Defined herpes simplex virus type 1 (HSV-1) mutants KOS/1 and KOS/62 (positive and negative, respectively, for latency-associated transcripts [LATs]) express the Escherichia coli beta-galactosidase (beta-Gal) gene during latency. These mutants were employed to assess the functions of the latency-associated transcription unit on establishment and maintenance of and reactivation from the latent state. It was found that in the trigeminal ganglia, the frequencies of hyperthermia-induced reactivation of KOS/62 and an additional LATs- mutant (KOS/29) were reduced by at least 80%. Quantification of latently infected neurons expressing the beta-Gal gene revealed that the LATs- mutant KOS/62 established approximately 80% fewer latent infections in the trigeminal ganglia than did KOS/1 (LATs+). This reduction in establishment which is evident in the trigeminal ganglia could account for the reduced frequency of reactivation from this site. In striking contrast, both LATs- mutants reactivated with wild-type frequencies from lumbosacral ganglia. Quantification of beta-Gal-positive neurons at this site revealed that KOS/62 established as many as or more latent infections than the LATs+ virus, KOS/1. Colocalization of HSV antigen and beta-Gal suggested that the decreased establishment by LATs- mutants in trigeminal ganglia was the result of inefficient viral shutoff. Thus, one function of the HSV-1 LATs transcription unit is to promote the establishment of latency in trigeminal but not lumbosacral ganglia. Such a function may be relevant to understanding the distinct clinical recurrent disease patterns of HSV-1 and HSV-2.

Animals

Effects of hyperbaric environment on human auditory middle latency response (MLR) and short latency somatosensory evoked potential (SSEP).

Hyperbaric chamber dives at 19 ATA with helium-oxygen were performed at the Japan Marine Science Technology Center from November 15 to December 3 in 1988 and from January 25 to February 4 in 1989. During simulated underwater experiments, auditory middle latency responses (MLRs) and short latency somatosensory evoked potentials (SSEPs) were recorded in 3 professional divers (2 divers in each dive) for assessment of brain function. During the saturation dive (180 m below sea level) component Pa on MLR was lost, while component Po remarkably increased in amplitude. These MLR changes rapidly recovered between the beginning of decompression and at about 90 m below sea level. On the other hand, N9-N20 interpeak latency on SSEP slightly or moderately increased in the both divers, but N9-N14 interpeak latency was not affected by the 19 ATA saturation dive. These results suggest that the hyperbaric environment corresponding to 180 m below sea level cause some cerebral dysfunctions, probably between the brainstem and the cortex, but these dysfunctions are only transient.

Adult

[Short-latency and long-latency muscle reflex responses in man].

In a group of 70 healthy subjects the author examined repeatedly the reflex response from the m.interosseus dorsalis I during middle voluntary contraction of the muscle induced by electrical stimulation of the dermal branches of the nn. digitalis of the index finger. The aim of the reflexological investigation was analysis of some electrophysiological properties of short-latency (SL) and long-latency (LL) reflex responses which could be identified as excitation and inhibition modulations of the recorded muscular activity after rectification and averaging of the electromyogram. The results of the analysis revealed a constant intraindividual shape and latencies of the SL and LL components of the reflex responses (30 ms, 50 ms resp.), regardless whether one or several different frequencies of stimulation were used. The SL reflex response in the distal muscles of the upper extremity is compatible with the spinal loop; the latency of the LL response is shorter than the voluntary reaction time for the small muscles of the hand, therefore its reflex origin is assumed.

Adult

Factors that affect the amplitudes and latencies of the vertex short latency acoustic responses in the cat.

The latencies and amplitude of the short latency (less than 10 msec) acoustic evoked responses recorded from the vertex of the cat have been studied as a function of acoustic stimulus parameters. A change in the stimulus intensity, duration, or rate of repetition resulted in parallel changes in the first 5 evoked responses, i.e., the latencies shifted the same amount and the amplitudes were modified in the same proportion. Comparison of responses to monaural versus binaural stimuli indicated an occlusive effect of binaural stimulation only in potential 4.

Acoustic Stimulation

Fine mapping of the latency-related gene of herpes simplex virus type 1: alternative splicing produces distinct latency-related RNAs containing open reading frames.

The latency-related (LR) gene of herpes simplex virus type 1 (HSV-1) is transcriptionally active during HSV-1 latency, producing at least two LR-RNAs. The LR gene partially overlaps the immediate-early gene ICP0 and is transcribed in the opposite direction from ICP0, producing LR-RNAs that are complementary (antisense) to ICP0 mRNA. The LR gene is thought to be involved in HSV-1 latency. We report here the fine mapping and partial sequence analysis of this HSV-1 LR gene. 32P-labeled genomic DNA restriction fragments and synthetic oligonucleotides were used as probes for in situ hybridizations and Northern (RNA) blot hybridizations of RNA from trigeminal ganglia of rabbits latently infected with HSV-1. The two most abundant LR-RNAs appeared to share their 5' and 3' ends and to be produced by alternative splicing. These LR-RNAs were approximately 2 and 1.3 to 1.5 kilobases in length and were designated LR-RNA 1 and LR-RNA 2, respectively. Their 5' ends started approximately 1,210 nucleotides downstream from the 3' end of the ICP0 mRNA. Their 3' ends overlapped ICP0 by nearly 1,000 nucleotides. LR-RNA 1 appeared to have at least one intron removed, while LR-RNA 2 appeared to have at least two introns removed. The LR-RNAs contained two potential long open reading frames, suggesting the possibility that one or more of the LR-RNAs may be a functional mRNA.

Animals

[Estimation of cancer latency using data from a case-control study with time-related factors--estimated latency for consumption of alcohol and tobacco in relation to gastric cancer].

As a practical application of theory, the susceptible exposure age and latency distribution of consumption of alcohol and tobacco in relation to stomach cancer is discussed. It was revealed that, in univariate, estimation of the susceptible exposure age of alcohol and tobacco were 15-50 years and 35-50 years. The estimated latency were 35 years and 15 years. Those of accumulative period and preneoplastic period were 30 and 10 years. In a multivariate analysis, the latency for alcohol consumption was changed to 20 years as the incubation time in preneoplastic period was prolonged by 5 years due to consumption of vegetables. This could give a theoretical interpretation of second line cancer prevention.

Adult

Repeater F waves: a comparison of sensitivity with sensory antidromic wrist-to-palm latency and distal motor latency in the diagnosis of carpal tunnel syndrome.

Thirty-five thousand six hundred supramaximal shocks were applied to 209 healthy and 147 entrapped median nerves (carpal tunnel syndrome--CTS) to characterize the backfiring behavior of the alpha motor neuron pool of abductor pollicis brevis in health and the modifying effect of a compressive neuropathy. A contraction of the normal subpopulation of active F-wave generators was found in CTS, while active neurons backfired at higher than normal frequencies (p less than 0.001). These modifications in spinal behavior are reflected in the % Repeater F-wave value, whose sensitivity in the detection of CTS approaches that of sensory wrist-to-palm latency estimation. This technique offers an alternative to latency measurement in the diagnosis of CTS. An economical strategy for the electrodiagnosis of CTS is proposed.

Adolescent

[Inter-individual variability of mean latencies in the dynamic topography of short latency visual evoked potentials and the origin of brainstem potentials evaluated by the dipole tracing method in normal subjects].

To determine the normal pattern of the short latency visual evoked potentials (SVEP) in clinical diagnosis, in a previous report, the normal responses were classified into the following three types: uniform type, brainstem dominant type and occipital dominant type, according to the strength of the potentials. In the present report the latencies of N40 and P50, which constitute the SVEP, were investigated. In addition, the burst origin of these potentials was investigated using the dipole tracing method for P50 obtained through dynamic topography. Optic nerve potentials of N40 appeared first in the anterior region (from 37.1msec to 40.4msec following the stimulus) after the fourth retinal oscillatory potentials and soon extended to the posterior region (after about 2msec). This potential appeared in approximately about 65%, because of the low amplitude. P50 appeared 45.8-53.6msec after the stimulus about 100% and burst 2-4 times in the same place. Using the dipole tracing method, the origin of P50 was estimated to the near the deep center of the brain, probably around the brainstem. The same results were obtained using dynamic topography.

Adult

A herpes simplex virus type 1 variant, deleted in the promoter region of the latency-associated transcripts, does not produce any detectable minor RNA species during latency in the mouse trigeminal ganglion.

In peripheral sensory ganglia latently infected with herpes simplex virus type 1 (HSV-1) transcription is restricted. A set of viral latency-associated transcripts, the LATs, have been characterized by Northern blotting and in situ hybridization. These transcripts have previously been mapped to a 3 kb region of the viral genome within the repeat long region. However, transcription from adjacent regions of the genome can be detected by in situ hybridization, which cannot be detected by Northern blotting. These RNAs are termed minor LATs or m-LAT. In this study we show that in ganglia latently infected with the HSV-1 variant 1704, which is deleted in one complete copy of the LAT gene and in the promoter and 5' portion of the other copy, m-LATs are not detected by in situ hybridization. Furthermore, the levels of DNA in nervous system tissue latently infected with the parental and the 1704 variant virus are similar. Thus we propose that the sequence elements necessary for initiating transcription or stabilizing m-LATs are within the region deleted in variant 1704 that codes for the promoter and the 5' end of the LATs.

Animals

[Measurement and clinical using of motor conduction latency time and motor conduction latency rate of facial nerve in health subjects and facial paralysis patients].

The motor conduction latency time (MCLT) and rate (MCLR) of facial nerve in 70 cases of health subjects and 60 cases of facial paralysis patients were measured using evoke EMG. The results showed that MCLT is below 4 ms and MCLR is above 25 m/sec in 70 cases of health subjects, while the MCLT is above 4 ms and MCLR is below 25 m/sec in 60 cases of facial paralysis patients. We have observed the difference of MCLR and MCLR on different age groups in health subjects. The results showed that MCLT is prolonged gradually and MCLR is gradual reduced after 50 years old groups. But the MCLT does not exceed 4 ms and MCLR is not slower than 25 m/sec. The results of this studies suggested that if MCLT is above 4 ms, and MCLR is below 25 m/sec, it is a index of facial nerve paralysis.

Adolescent