抗家鼠型肾综合征出血热病毒单克隆抗体对感染乳鼠保护作用的初步研究

以家鼠型HFRS病毒R22株100LD_(50)感染2～4日龄乳鼠。于感染后0、48、96及120h分别经腹腔注射对该株病毒具有中和活性的单一McAb或混合McAb,同时设该病毒免疫血清、单注射该病毒和Sp2/0腹水3种对照,观察McAb对感染乳鼠的保护作用,观察时间为35d。结果在感染后96h内注射单一McAb、混合McAb及免疫鼠血清的保护率均可达100％,而Sp2/0腹水对照组与病毒对照组的乳鼠均在感染后第13～16d发病死亡。在死亡乳鼠的脑,肺组织中检出了HFRS病毒抗原,而在保护存活乳鼠的脑、肺组织中均未检出病毒抗原。McAb对感染乳鼠的保护率与其浓度相关。在感染后24h分别注射不稀释、10~(-1)、10~(-2)和10~(-3)稀释的混合McAb,其保护率依次为100％、88.7％、55.6％和16.7％。     

Circadian‐ and temperature‐specific effects of early deprivation on rat maternal care and pup development: Short‐term markers for long‐term effects?

We compare the effects on pup body weight and on maternal care of 4-hr separation from dam and littermates on postnatal Days 1 to 14 (early deprivation, ED) under different thermal and circadian conditions. ED was performed at either 21 degrees C (Cold), or 32 degrees C (Warm), and either during the light or dark phase. The comparison group was nonhandling (NH), either under a nonreversed (Light) or reversed (Dark) cycle. At weaning, Cold ED pups were of lower body weight than Warm ED pups, and Warm ED pups were of lower body weight than NH pups. Light and Dark ED pups received high care at reunion relative to NH, and Cold ED pups received higher care at several hours postreunion relative to Warm ED and NH pups. We propose that reduced pup weight and increased maternal care are short-term markers for the severity of Cold ED, and that this manipulation could therefore impact negatively on emotionality and cognition in adulthood.     

不同剂量病毒唑治疗肾综合征出血热306例疗效分析

应用不同剂量病毒唑对３０６例肾综合征同血热患者进行治疗对比观察，发现两治疗组疗效无显著性差异，但两治疗组怀对照组相比，越期率高，肾功能恢复快，血小板数恢复早，病程缩短，并发症减少，病死率也有所下降，但无显著性差异。     

母血与脐血血清游离氨基酸谱的比较

本实验取在分娩过程中的50对健康足月妊娠母亲的静脉血与其分娩的胎儿脐带血分别测定其血清中游离氨基酸的浓度,发现:(1)脐血中绝大多数氨基酸的浓度都显著高于母血。(2)分娩中产妇血清游离氨基酸总浓度高于非妊娠育龄妇女。(3)男性胎儿和女性胎儿的脐血氨基酸浓度除胱氨酸以外均无显著性差异。     

Correlation between cyclophosphamide-induced viral susceptibility and depletion of Junin virus-induced suppressor populations.

In contrast to lymphocytic choriomeningitis virus, another arenavirus, Junin virus (JV), the etiologic agent of Argentine hemorrhagic fever, when inoculated into suckling mice, induces lethal meningoencephalitis characterized by a delayed-type hypersensitivity (DTH)-like immune response. However, the adult BALB/c mouse is resistant to infection and no DTH reaction can be seen. This different viral sensitivity may be related to the development of an antigen non-specific DTH-suppressor cell pathway at work in the adult mouse. When the resistant mice are treated with cyclophosphamide (Cy) (50 mg/kg each dose) given at days -1,+1,+4 (zero: infection day), animals become susceptible and develop DTH reaction in brain that leads to death. We analyze the influence of the timing of Cy administration on the suppressor system developing after infection. It was found that Cy depletes the previously described JV-induced suppressor populations (Tsv) but a new suppressor cell (Tsv*) is disclosed bearing the Thy 1+ Ly1+2- phenotype which is unable to depress DTH in Cy-treated animals. With only two doses of Cy corresponding to days -1 and +1, the target of Tsv* cells is depleted but the third dose is still required to achieve full depletion of Tsv cells which are able to employ the Cy-resistant antigen-specific suppressor cells as targets. Since the Cy treatment is able to deplete the Tsv population together with the target of Tsv* cells, animals became unable to regulate lethal DTH reaction. Thus, a cellular explanation for an empirically established Cy schedule able to abrogate the adult mouse resistance to JV is proposed.     

Human cytomegalovirus, human herpesvirus-6 and human herpesvirus-7 in neutropenic patients with fever of unknown origin

Objective  To investigate the appearance of cytomegalovirus (CMV) DNA, human herpesvirus-6 (HHV-6) DNA and human herpesvirus-7 (HHV-7) DNA in plasma as a sign of reactivation and possible causes of fever of unknown origin (FUO) during neutropenia.
Methods  From 134 patients with febrile neutropenia following cytotoxic chemotherapy during the years 1996–2000, 20 severely neutropenic patients (granulocyte count < 0.1 × 10⁹/L) were selected. Ten were patients with bacteremia and ten were patients with FUO. Five samples from each patient were selected at the start of chemotherapy, at the time of blood culture and fever, after 24 and 48 hours of fever, and, finally, after two to three days without fever. Virus DNA was detected by real-time quantitative and nested polymerase chain reaction (PCR).
Results  CMV-DNA was detected in two out of ten FUO-patients in all samples drawn during fever. From another FUO and during two bacteremia episodes, CMV-DNA was detected after 48 hours of fever. DNA from HHV-6 and HHV-7 was not detected in any of the 20 febrile episodes.
Conclusions  HHV-6 and HHV-7 as a possible explanation for FUO in severely neutropenic patients treated with cytotoxic chemotherapy seems not be very likely. However, CMV was identified in 5/20 patients and the febrile episodes in the two FUO-patients with constant DNA-emia may have been caused by a reactivation of CMV. This implies that CMV infection can be expected not only in transplant patients but also in chemotherapy-treated neutropenic patients.     

Behavioral development in mice: Effects of maternal environment and the albino locus

We examined the interaction of the albino locus with the maternal environment on the behavioral development of two coisogenic strains of mice. Subjects of the pigmented C57BL/6 strain (=B6^+/+) and of the albino C57BL/6^c2J strain (=B6^c/c) were either fostered by a mother of their own strain or cross-fostered at birth to an F₁ hybrid dam. They were compared for the amount and daily distribution of activity displayed during 48 h in a seminatural device at weaning and when 75 days old. Food hoarding in the nest and food consumption at the food-search place were also recorded in adult subjects. When animals were fostered by a mother of their own strain, albino mice were more active and less nocturnal than pigmented mice at both ages. They hoarded less food in the nest and ate more at the food-search place. Most of these differences disappeared when both strains were fostered by an F₁ dam. The amount of activity displayed during 48 h increased between 21 and 75 days of age. This increase was affected by cross-fostering to an F₁ dam in B6^c/c mice only. The developmental pattern of daily distribution of activity was changed by F₁ dams in B6^+/+ mice only. Whereas these influences of F₁ dams produced subjects resembling the mother's phenotypic score, maternal effects on hoarding behavior in B6^c/c mice produced subjects which did not resemble their foster mother. The results are discussed in terms of different possible ways of hereditary transmission of behavior and some methodological consequences are emphasized.     

Cell-free fetal DNA and intact fetal cells in maternal blood circulation: implications for first and second trimester non-invasive prenatal diagnosis

Both intact fetal cells as well as cell-free fetal DNA are present in the maternal circulation and can be recovered for non-invasive prenatal genetic diagnosis. Although methods for enrichment and isolation of rare intact fetal cells have been challenging, diagnosis of fetal chromosomal aneuploidy including trisomy 21 in first- and second-trimester pregnancies has been achieved with a 50-75% detection rate. Similarly, cell-free fetal DNA can be reliably recovered from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and paternally derived single gene mutations. Real-time PCR assays are robust in detecting low-level fetal DNA concentrations, with sensitivity of approximately 95-100% and specificity near 100%. Comparing intact fetal cell versus cell-free fetal DNA methods for non-invasive prenatal screening for fetal chromosomal aneuploidy reveals that the latter is at least four times more sensitive. These preliminary results do not support a relationship between frequency of intact fetal cells and concentration of cell-free fetal DNA. The above results imply that the concentration of fetal DNA in maternal plasma may not be dependent on circulating intact fetal cells but rather be a product of growth and cellular turnover during embryonic or fetal development.     

Fever-like temperature induces maturation of dendritic cells through induction of hsp90

Fever is a phylogenetically conserved biological phenomenon and a common consequence of infection. Here, we examine in vitro and in vivo the effect of febrile temperature on dendritic cells (DC), a key antigen-presenting cell in the immune system. Elevated temperatures are observed to cause immature DC to mature, specifically through elevation of intracellular levels of hsp90. Surprisingly, even brief exposure to elevated temperatures has a powerful effect on the immunostimulatory capacity of DC. These results bear on the mechanisms of the salutary effects of fever as well as of behavioral elevations of temperature such as saunas and warm blankets.