高危人乳头瘤病毒基因变异与宫颈癌的关系

近年来 ,高危人乳头瘤病毒 (HPV)基因变异和宫颈癌进展的关系日益受到重视。已经发现了一些可能对诊断和治疗有参考意义的基因变异。本文对高危HPV的重要变异与表达调控、细胞转化及永生化、免疫反应等改变在宫颈癌进展中的研究进行了综述     

The specific features of circadian blood pressure variations in patients with hypertensive disease in different types of weather

The specific features of circadian blood pressure (BP) variations were studied in 162 patients aged 20 to 60 years who had hypertensive disease (HD) in the warm period of a year in different types of weather. In accordance with the type of weather in which daily BP monitoring (DBPM) was performed, the examinees were divided into 2 groups: 1) those examined in droughty (anticyclonic) weather; 2) those examined in moist (cyclonic) weather, The groups were matched by the number (81) of patients, age, gender, duration of the disease, and office BP values. The mean BP during a day, daylight and night hours, the maximum and minimum BP during wake and sleep was significantly high in moist weather. Examining the magnitude of a nocturnal BP decrease indicated that in Group 1, its adequate decrease (the dipper daily curve) was recorded in 72.3% of the patients; inadequate BP decrease (the non-dipper daily curve) was in 24.2%; paradoxical nocturnal hypertension (night peaker) was seen in 1.8%. In Group 2, adequate and inadequate nocturnal BP decreases were observed in 44.4 and 41.3%, respectively; paradoxical nocturnal hypertension was in 7.7%. Statistical processing confirmed the validity of the findings. Moist (cyclonic) weather was ascertained to be marked by the changes in adequate circadian BP variations: a significant mean daily, maximum, and minimum systolic BP (SBP) and diastolic BP (DBP), as well as by the inadequate nocturnal lowering of SBP and DBP, which determines a poor prognosis and may serve as a basis for preventing HD complications in this period of a year.     

Measuring circadian temperature rhythm

Experimental control and mathematical techniques increase confidence that results of circadian temperature rhythm studies reflect true changes in the circadian timing system versus coupling with exogenous synchronizers. Masking effects represent confounding influences in studies that are concerned with the endogenous temperature rhythm. Because it is technically difficult to measure directly the behavior of the endogenous timing system, marker rhythms are used as proxy measures. However in addition to entraining, the external environment exerts a direct masking effect on the monitored rhythm. Methods for measuring circadian temperature rhythm are reviewed in this article. Constant routine, forced desynchrony, and purification methods represent attempts, at an experimental or mathematical level, to remove masking effects and more accurately capture the endogenous circadian temperature rhythm. Exogenous factors have not been subjected to the same scrutiny as the endogenous features of circadian temperature rhythm. But it is the environmental context, the extent to which the endogenous features are adaptively modified by the field environment, that will ultimately determine the biological value of circadian temperature rhythm to the organism. Thus, nurse investigators are encouraged to use rigorous methods to study both endogenous circadian temperature rhythm and exogenous rhythms.     

The circadian clock in mammals

The basic physiological and anatomical basis for circadian rhythms in mammalian behaviour and physiology is introduced. The pathways involved in photic entrainment of the circadian clock are discussed in relation of new findings that identify the molecules that are involved in signalling between the environment and the clock. The molecular basis of endogenous cycles is described in the mouse, and compared to the mechanism that is present in the fly. Finally we speculate on the relationship between circadian physiology and pain.     

The circadian clock in mammals

The basic physiological and anatomical basis for circadian rhythms in mammalian behaviour and physiology is introduced. The pathways involved in photic entrainment of the circadian clock are discussed in relation of new findings that identify the molecules that are involved in signalling between the environment and the clock. The molecular basis of endogenous cycles is described in the mouse, and compared to the mechanism that is present in the fly. Finally we speculate on the relationship between circadian physiology and pain.     

The circadian clock in mammals

The basic physiological and anatomical basis for circadian rhythms in mammalian behaviour and physiology is introduced. The pathways involved in photic entrainment of the circadian clock are discussed in relation of new findings that identify the molecules that are involved in signalling between the environment and the clock. The molecular basis of endogenous cycles is described in the mouse, and compared to the mechanism that is present in the fly. Finally we speculate on the relationship between circadian physiology and pain.     

Normal sleep and circadian processes

The onset of sleep is associated with a variety of changes in both behavioral and physiologic states. Sleep is not a uniform state either: it has different stages that affect different areas of the brain and body. Nonrapid eye movement sleep stages are as different from rapid eye movement sleep as is wakefulness. Circadian rhythms of physiologic systems also impact wake, sleep, sleepiness, and alertness. There are characteristic changes in both sleep patterns and circadian rhythm that occur with aging. The cardiovascular, respiratory, endocrine and gastrointestinal systems also undergo changes with sleep onset. This article reviews the aspects of normal sleep, physiologic changes that occur in the human body with sleep, and how sleep changes over the lifespan.     

Sleep and circadian schedule disorders

The timing and synchronization of human circadian rhythms is important for health and well-being. Some individuals, for reasons that remain unclear, display less resilience or flexibility in their ability to synchronize to the 24-hour world and are thus diagnosed with a circadian schedule disorder. The objective of this article is to briefly introduce concepts about human circadian timing and to review what is known about chronic, long-term circadian schedule disorders such as delayed sleep phase syndrome, advanced sleep phase syndrome, irregular sleep-wake patterns, and non-24-hour sleep-wake disorder. Practical considerations for the clinician caring for these individuals are discussed.     

Human platelet thermostable phenol sulfotransferase from blacks and whites: biochemical properties and variations in thermal stability

Phenol sulfotransferase (PST) catalyzes the sulfate conjugation of catecholamines and of phenolic drugs. Human platelet PST exists in at least a thermolabile form (TL PST) and a thermostable form (TS PST). The mean basal level of platelet TS PST activity in samples from American blacks is significantly higher than the basal activity in samples from whites. We carried out the studies reported here to determine whether the higher basal TS PST activity in platelet homogenates from blacks was biochemically similar to the lower basal activity in samples from whites. We also characterized variations in TS PST thermal stability. Platelet TS PST activities in samples from the two groups were almost identical with respect to pH optima, Michaelis-Menten constant values for substrates, and susceptibilities to inhibition by 2,6-dichloro-4-nitrophenol and sodium chloride. Thermolabile and thermostable TS PST were present in samples from both blacks and whites. Thermal stabilities of TS PST in samples from 167 volunteers (104 blacks, 63 whites) were expressed as heated sample-to-control sample ratios. Bimodal frequency distribution histograms of the heated-to-control ratios revealed subgroups of samples with thermolabile TS PST activities from 13.5% of blacks (heated-to-control ratio less than 0.32) and 12.7% of whites (heated-to-control ratio less than 0.27). The mean heated-to-control ratio for thermostable TS PST from blacks was significantly higher than that from whites (0.52 +/- 0.01 vs 0.43 +/- 0.01, respectively, mean +/- SEM; p less than 0.0001). Our studies demonstrated the similarity of biochemical properties of platelet TS PST at the extremes of basal activity. They also showed equivalent subgroups of blacks and whites with thermolabile TS PST. The results are an important initial step toward testing the hypothesis that inheritance may be one factor in the regulation of basal levels of activities and thermal stabilities of platelet TS PST from American blacks.     

Interconnections between circadian clocks and metabolism

Circadian rhythms evolved through adaptation to daily light/dark changes in the environment; they are believed to be regulated by the core circadian clock interlocking feedback loop. Recent studies indicate that each core component executes general and specific functions in metabolism. Here, we review the current understanding of the role of these core circadian clock genes in the regulation of metabolism using various genetically modified animal models. Additionally, emerging evidence shows that exposure to environmental stimuli, such as artificial light, unbalanced diet, mistimed eating, and exercise, remodels the circadian physiological processes and causes metabolic disorders. This Review summarizes the reciprocal regulation between the circadian clock and metabolism, highlights remaining gaps in knowledge about the regulation of circadian rhythms and metabolism, and examines potential applications to human health and disease.

To adapt to daily environmental changes caused by our Earth’s rotation, most organisms on the planet evolved near-24-hour cycles of behavioral, physiological, and metabolic rhythms (1). In addition to the entrained environmental stimuli, the internal timekeeping system of the circadian clock has evolved to anticipate external changes (2, 3). These conserved rhythms synchronize internal biological and behavioral processes to the external temporal environment, presumably providing organisms with selective advantages for survival. However, over the past century, modern industrialized society has profoundly changed our external environment (4). For example, the boundaries between day and night have been blurred by electric light and travel across different time zones. Disrupted circadian rhythms are highly associated with metabolic disorders (5). Conversely, obesity induced by overeating or overnutritional environment leads to circadian remodeling (6, 7). Understanding the reciprocal regulation of circadian rhythm and metabolism may provide mechanistic insights into circadian physiology and advance new chronotherapy approaches and therapeutic targets for metabolic disorders.     

Physiologic circadian rhythmicity in preterm infants

This study investigated evidence of a circadian rhythm in the physiologic variables of transcutaneous oxygen (tcPO2) level, pulse rate, respiratory rate, frequency of respiratory pauses, and skin temperature in six 34- to 37-week-preterm infants. A value for each variable was noted every 30 minutes for 24 hours, providing 245 observations for each infant. An adaptation of cosinor analysis, a least squares procedure that determines the cosine curve for a 24-hour period that best fits the observed pattern of values, was applied to the data. Statistically significant circadian rhythmicity was found for five of the six subjects with regard to skin temperature. Significant circadian rhythm was also demonstrated in two or three patients for all other variables. No significant consistent synchrony for individual variables across subjects was found. Actual peak values of respiratory pause frequency and trough values of tcPO2, however, occurred between midnight and 4:30 A.M. for every infant. Preterm infants exhibited evidence of a circadian rhythm in skin temperature, and tcPO2 and respiratory pause frequency exhibited day/night pattern characteristics.     

Differences between young and elderly subjects in seasonal and circadian variations of total plasma proteins and blood volume as reflected by hemoglobin, hematocrit, and erythrocyte counts

Circadian and seasonal rhythms in total plasma proteins were documented in healthy young men (around 24 years old), and in elderly subjects (both sexes), including senile-dementia patients in their eighties. The concentration of plasma proteins within a given group changed predictably (7-13%), depending on the hour of sampling and the season. Concentrations decreased noticeably around 04:00 h, then peaked around 08:00 h (shortly after waking). The 24-h mean concentrations of total plasma proteins were lower in the elderly groups than in the young men. But the seasonal variations of the 24-h mean values were strikingly larger in the elderly groups (7-8 g/L) than in the young men (2-5 g/L). Moreover, the circadian profiles of plasma proteins differed from the profiles of hematocrit, hemoglobin, and erythrocyte counts. Evidently, circadian variations of blood volume may not be the only element accounting for the variations of plasma protein concentrations. We suggest that the rhythms in plasma protein concentrations be taken into account when reference values are set. Circadian and seasonal variations in plasma proteins may also significantly affect the transport and binding of drugs, especially in the aged.     

Prospects for circadian treatment of mood disorders

Abstract

Disruption of circadian clocks is strongly associated with mood disorders. Chronotherapies targeting circadian rhythms have been shown to be very effective treatments of mood disorders, but still are not widely used in clinical practice. The mechanisms by which circadian disruption leads to mood disorders are poorly characterized and, therefore, may not convince clinicians to apply chronotherapies. Hence, in this review, we describe specific potential mechanisms, in order to make this connection more credible to clinicians. We believe that four major features of disrupted clocks may contribute to the development of mood disorders: (1) loss of synchronization to environmental 24-h rhythms, (2) internal desynchronization among body clocks, (3) low rhythm amplitude, and (4) changes in sleep architecture. Discussing these attributes and giving plausible examples, we will discuss prospects for relatively simple chronotherapies addressing these features that are easy to implement in clinical practice.

• Key messages

• In this review, we describe specific potential mechanisms by which disrupted clocks may contribute to the development of mood disorders: (1) loss of synchronization to environmental 24-h rhythms, (2) internal desynchronization among body clocks, (3) low rhythm amplitude, and (4) changes in sleep architecture.

• We provide prospects for relatively simple chronotherapies addressing these features that are easy to implement in clinical practice.