Estrogen-induced maternal behavior in hysterectomized-overiectomized virgin rats.

A single injection of 100 μg/kg estradiol benzoate (EB) either alone or in combination with 0.5 mg progesterone resulted in a significant reduction in the latency for the onset of maternal behavior in hysterectomized-ovariectomized virgin rats as compared to the latencies of groups which either remained intact or were hysterectomized, hysterectomized-ovariectomized, hysterectomized-ovariectomized and treated with 20 μg/kg EB, or ovariectomized-sham hysterectomized and injected with 100 μg/kg EB. In contrast to recent research, there was no shortening of the maternal latencies when ovariectomy or combined hysterectomy-ovariectomy was performed 8 weeks prior to testing while the administration of EB 8 weeks postoperatively was still effective in stimulating short-latency maternal care in hysterectomized-ovariectomized females and increased the percentage of ovariectomized sham hysterectomized animals responding maternally. It was concluded that estrogen is capable of inducing, not suppressing, maternal behavior in virgin rats and that the uterus may play an important but as yet undetermined role.     

Spinal neuronal inhibition and EEG synchrony by electrical stimulation in subcortical forebrain regions of the cat

Summary In cats anaesthetized with sodium pentobarbital and 70% N₂O, single lumbar dorsal horn neurons were excited by controlled noxious radiant heating of glabrous hindpaw skin. The EEG was recorded from the pericruciate cortex and posterior lateral gyrus. Subcortical forebrain sites where electrical stimulation inhibited dorsal horn neuronal heat-evoked responses contralaterally were identified by mapping the caudate nucleus, internal capsule, septum, nucleus accumbens and basal forebrain regions. Inhibitory sites were mainly located in the ventral forebrain (ventral septum, diagonal band, basal forebrain). The caudate nucleus and internal capsule had a low incidence and effectiveness of inhibitory sites. In the basal forebrain, the incidence and effectiveness of inhibitory sites decreased from caudal to rostral regions. There was a rostral limit of inhibitory sites, both medially and laterally. The magnitude of inhibition increased with graded increases in brain stimulation intensity. The mean incremental increase in inhibition was greater for caudal than for rostral basal forebrain sites. Mean stimulus currents for threshold of inhibition and for inhibition to 50% of control heat responses were lower for caudal than for rostral sites. Responses of the dorsal horn neurons to increasing temperatures of noxious skin heating were monotonic linear functions over the temperature range studied (48–53° C). Stimulation in both rostral and caudal basal forebrain decreased the slope of this stimulus-response function, with a greater decrease for caudal sites. Cortical EEG synchronization was evoked by stimulation in the caudate nucleus and rostral basal forebrain. For both regions, most synchronogenic sites did not produce descending inhibition of dorsal horn neurons. The significance of these findings in relation to descending inhibition from other brain regions and stimulation-produced analgesia is discussed.     

Multiple signal transduction pathways activated through the T cell receptor for antigen.

The T cell receptor for antigen (TCR) is a multichain complex on the surface of T lymphocytes which binds peptide antigen and transduces a transmembrane signal leading to IL-2 secretion. Engagement of the TCR leads to activation of a tyrosine phosphorylation pathway and a phospholipase C (PLC) pathway leading to activation of protein kinase C (PCK). Currently available data suggest that the primary event in signal transduction is tyrosine kinase activation, since when this pathway is inhibited, PLC activation is blocked and there is no production of IL-2. The nature of the tyrosine kinase which initiates the signaling cascade is currently unknown. The CD4/CD8 associated kinase p56lck clearly plays a role in tyrosine phosphorylation, but it is clearly not the only tyrosine kinase involved. Studies demonstrating physical association of p59lyn with the TCR implicate fyn as an important candidate for the TCR tyrosine kinase. The protein tyrosine phosphatase CD45 also plays a critical early role in signal transduction since in cells where it is deficient, neither tyrosine kinase activation nor later signaling events are seen. The importance of the PLC/PKC pathway is illustrated by the fact that activation of this pathway alone may lead to IL-2 production. However, there may also be other mechanisms which can generate an IL-2 response. Two proteins known to be involved in growth regulation--p21ras and c-raf--have now been shown to be downstream targets of the PLC/PKC pathway.     

Analysis of sequence-tagged-connector strategies for DNA sequencing

The BAC-end sequencing, or sequence-tagged-connector (STC), approach to genome sequencing involves sequencing the ends of BAC inserts to scatter sequence tags (STCs) randomly across the genome. Once any BAC or other large segment of DNA is sequenced to completion by conventional shotgun approaches, these STC tags can be used to identify a minimum tiling path of BAC clones overlapping the nucleation sequence for sequence extension. Here, we explore the properties of STC-sequencing strategies within a mathematical model of a random target with homologous repeats and imperfect sequencing technology to understand the consequences of varying various parameters on the incidence of problem clones and the cost of the sequencing project. Problem clones are defined as clones for which either (A) there is no identifiable overlapping STC to extend the sequence in a particular direction or (B) the identified STC with minimum overlap comes from a nonoverlapping clone, either owing to random false matches or repeat-family homology. Based on the minimum overlap, we estimate the number of clones to be entirely sequenced and, then, using cost estimates, identify the decision rule (the degree of sequence similarity required before a match is declared between an STC and a clone) to minimize overall sequencing cost. A method to optimize the overlap decision rule is highly desirable, because both the total cost and the number of problem clones are shown to be highly sensitive to this choice. For a target of 3 Gb containing approximately 800 Mb of repeats with 85%-90% identity, we expect <10 problem clones with 15 times coverage by 150-kb clones. We derive the optimal redundancy and insert sizes of clone libraries for sequencing genomes of various sizes, from microbial to human. We estimate that establishing the resource of STCs as a means of identifying minimally overlapping clones represents only 1%-3% of the total cost of sequencing the human genome, and, up to a point of diminishing returns, a larger STC resource is associated with a smaller total sequencing cost.     

Significance of hypoalbuminemia in pediatric oncology patients--malnutrition or infection?

Nutritional status was evaluated on 210 occasions in 90 pediatric oncology inpatients during a 7-month period; 39 had solid tumors and 51 leukemia. Ages ranged from 3 months to 20 yr. Nutritional parameters were defined as normal, "at risk," or "probably malnourished." Fifty-seven and 29% of assessments revealed at least one parameter "at risk" or "probably malnourished," respectively. Prognosis was negatively related to the number of abnormal nutritional parameters. Serum albumin was most frequently abnormal. However, on most occasions, hypoalbuminemia was associated with weight/height, arm muscle area, and triceps skinfold measurements in the normal range. In order to further identify determinants of serum albumin, we analyzed dietary, chemotherapy, and temperature data in 10 prospectively studied leukemia patients, half of whom received parenteral nutrition. In these patients there was little relationship of serum albumin to chemotherapy or dietary intake. In all of these patients, especially those receiving total parenteral nutrition, low serum albumin was highly associated with fever (p less than 0.0005). We concluded that febrile illness is an important determinant of abnormal serum albumin concentrations. In pediatric cancer patients, abnormal serum albumin may more often reflect the acute metabolic response to fever and infection than depletion of body mass.     

The effect of culture on how women experience menstruation: Jewish women and Mikvah

Mikvah is a practice in Judaism consisting of ritual bathing that occurs at the end of the menstrual period. This study compared 161 married Jewish women, 82 mikvah users, and 79 non-users in order to learn how this ritual affects attitudes towards menstruation and the perception of menstrual and premenstrual distress. Women participating in mikvah, a ritual that defines them as "unclean," were expected to have more negative conceptions of menstrual cycle symptomatology and more positive menstrual attitudes than women in the same culture not participating in this ritual. These hypotheses were not supported by the findings. What was found was a similarity between the two groups in attitudes towards menstruation, frequency and type of symptoms surrounding the menstrual period, and the degree to which any of these symptoms were experienced.     

Attenuation of ethanol tolerance by a novel stimulus

A Pavlovian conditioning model of tolerance emphasizes that an association between predrug cues and the systemic effects of the drug contributes to tolerance. On the basis of this model, established tolerance should be attenuated by external inhibition, i.e., by presentation of a novel, extraneous stimulus. This prediction was evaluated in the present experiment. Rats that were so tolerant to the hypothermic effect of ethanol that they evidenced no drug-induced decrease in temperature were presented with a bright strobe light following ethanol administration. The light precipitated a large decrease in temperature in these rats. These results provide further evidence that tolerance to the hypothermic effect of ethanol is, in part, mediated by learning.     

Pharmacokinetic transfer functions and generalized clearances

A generalized steady-state clearance coefficient is defined to relate drug or metabolite mass transfer rates into one area of the body (area II) to the constant drug concentration in another area (area I). It is demonstrated that this clearance coefficient may be used in the transient case to calculate total mass transfer into area II when the drug AUC in area I is known. This generalizes the well-known "clearance formula" CL = Ae/AUC to cases in which several compartments separate areas I and II, as well as to cases where distributed models are preferred. Several applications are discussed, including a noninvasive means of determining the fraction absorbed of topically administered drugs.     

Hostage hallucinations. Visual imagery induced by isolation and life-threatening stress

The literature on hallucinatory experiences of hostage victims is reviewed. The phenomenology is examined in 30 case studies involving 31 persons, including ex-prisoners of war and victims of rape, kidnapping, terrorism, robbery, and "UFO abductions." The victims were subjected to conditions of isolation, visual deprivation, restraint on physical movement, physical abuse, and the threat of death. For eight victims, these conditions were sufficient to produce a progression of visual hallucinations from simple geometric images to complex memory images coupled with dissociation. The other 23 victims, subjected to similar conditions but without isolation and life-threatening stress, resulting from the threat of death, did not experience hallucinations. The hostage hallucinations are compared to those resulting from sensory deprivation, near fatal accidents, and other states of isolation and stress. A common mechanism of action based on entoptic phenomena and CNS excitation and arousal is suggested.     

The Alpha-Defensin Prosthetic Joint Infection Test Has Poor Validity for Native Knee Joint Infection

BackgroundThe alpha-defensin test known as Synovaure has been very effective in diagnosis of prosthetic joint infections (PJIs). Being able to easily and accurately differentiate septic and inflammatory arthropathies in native joints would improve diagnostic workup and management. We tested the ability of an alpha-defensin test to distinguish septic from inflammatory or crystalline arthropathy in the native knee.Methods40 native knee joint fluid specimens were tested with cell count, fluid analysis, and culture and alpha-defensin testing. We determined the sensitivity and specificity of the alpha-defensin test using culture-positive fluid as the gold standard for septic arthropathy and positive crystals as the gold standard for crystalline arthropathy.ResultsThe Synovasure PJI test had 100% specificity for septic arthritis coupled with a 28% false-positive rate when applied to native knee aspirations. False-positive rate was 5.3 times higher in patients with crystals found in the joint fluid.ConclusionAlpha-defensin testing, in the form of the Synovasure PJI test, has a high-false-positive rate when used to distinguish septic and inflammatory arthritis in the native knee joint. Future work will need to determine the sensitivity and specificity of the newer native joint panel. Clinicians should be cognizant of the specific alpha-defensin test used when sampling native knee synovial fluid.