原发性肾病综合征患者抗心磷脂抗体的研究

检测６８例原发性肾病综合征和３０例正常人抗心磷脂抗体（Ａｃｌ抗体）。结果示：Ａｃｌ抗体阳性率分别为３２３５％和３３３％;阳性组的高凝状态及肾小球损伤比阴性组病人更为明显,且对治疗的敏感性也显著降低。提示Ａｃｌ抗体在原发性肾病综合征的发病及发展中可能有着重要的作用。     

Prospective study of microchimerism in transplant recipients

BACKGROUND: We evaluated peripheral blood microchimerism in 48 consecutive organ transplant recipients (35 kidneys, ten livers, one kidney-liver, one kidney-pancreatic islet, one kidney pancreas) up to 12 months post-transplantation. Patients were categorized according to the presence or absence of rejection episodes, and the patterns of microchimerism in the two groups were then compared. METHODS: DNA was extracted from donor, pre-transplant, and post-transplant peripheral blood samples. Several polymerase chain reaction (PCR)-based assays were developed for the detection of microchimerism. Assay sensitivities ranged from 0.0001 to 3%. RESULTS: Microchimerism was detected only in sex-mismatched cases (male donors and female recipients) using nested PCR for a Y-chromosome marker. There were ten such cases (six kidneys, two livers, and two combined organ transplants). In patients without rejection (n = 7), there was a peak of donor-DNA at 1-3 wk post-transplantation followed by a second peak between 3 wk and 4 months. In patients with biopsy-proven rejection (n = 3), the peaks were absent and the levels of microchimerism were extremely low (< 0.001%). Microchimerism levels declined in all 10 patients and were barely detectable 1 yr post-transplantation. Microchimerism was not detected in the remaining 38 patients despite using a battery of sensitive PCR-based assays. CONCLUSIONS: In our study, microchimerism was detected using the Y-chromosome PCR assay only and the level of donor-DNA in a given patient varied over time. This study highlights the difficulties in establishing a correlation between microchimerism and transplant tolerance.     

The involvement of an opiate mechanism in the sensitized behavioral deficit induced by early chronic variable stress: influence of desipramine

The influence of early chronic variable stress (CVS) associated with persistent desipramine (DMI) administration was examined on escape performance. Animals were exposed to CVS and 1 day later administered DMI (5 mg/kg, i.p. twice a day) or vehicle (VH) during six consecutive days. Escape performance was assessed over 24 h following inescapable shock (IS) exposure. Higher escape failures were observed in CVS shocked rats compared with unstressed shocked animals. DMI normalized escape failures in both groups. In order to investigate the role of an endogenous opiate mechanism presumably activated by CVS exposure in this behavioral deficit, rats were administered naltrexone (NAL, 2 mg/kg i.p.) or VH prior to each daily stressor of the CVS regime. NAL pretreatment blocked escape failures performed only by CVS shocked rats. In addition, animals were daily administered morphine (MOR, 10 mg/kg, i.p.) or VH during seven consecutive days and subsequently administered DMI. A significant increase in escape deficit in shocked rats was observed after chronic MOR but not following the associated treatment with MOR and DMI. These behavioral data suggest that early experience with a CVS facilitated the onset of escape deficit induced by a brief IS event, an effect that can be prevented by chronic DMI. Furthermore, this sensitized escape deficit response seems to be partially modulated by the previous activation of an opiate mechanism.     

Potentiation of glutamatergic agonist-induced inositol phosphate formation by basic fibroblast growth factor is related to developmental features in hippocampal cultures: neuronal survival and glial cell proliferation

We investigated the modulation by growth factors of phospholipase C (PLC)-linked glutamate receptors during in vitro development of hippocampal cultures. In defined medium, glial cells represent between 3 and 14% of total cell number. When we added basic fibroblast growth factor (bFGF) 2 h after plating, we found: (i) a neuroprotection from naturally occurring death for up to 5 days; (ii) a proliferation of glial cells from day 3; and (iii) a potentiation of quisqualate (QA)-induced inositol phosphate (IP) formation from 1 to 10 days in vitro (DIV) and 1S, 3R-amino-cyclopentane-1,3-dicarboxylate (ACPD) response from 3 to 10 DIV. The antimitotic cytosine-beta,D-arabinofuranoside (AraC) blocked glial cell proliferation induced by bFGF, but not neuroprotection. Under these conditions, the early potentiation of the QA response (1-3 DIV) was not changed, while the ACPD and late QA response potentiations were prevented (5-10 DIV). Epidermal growth factor was not neuroprotective but it induced both glial cell proliferation and late QA or ACPD potentiation. Surprisingly, the early bFGF-potentiated QA-induced IP response was blocked by 6, 7-dinitro-quinoxaline-2,3-dione (DNQX), suggesting the participation of ionotropic (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate (KA) receptors. The delayed bFGF-potentiated ACPD-induced IP response is inhibited by (S)-alpha-methyl-4-carboxyphenylglycine (MCPG), indicating possible activation of glial metabotropic receptors. These results suggest that, in hippocampal cultures, bFGF modulates AMPA and metabotropic glutamate receptors linked to the IP cascade, possibly in relation to the regulation of neuronal survival and glial cell proliferation, respectively.     

Perirhinal cortex input to the hippocampus in the rat: evidence for parallel pathways, both direct and indirect. A combined physiological and anatomical study

The possibility of a direct projection from the perirhinal cortex (PER) to areas CA1 and subiculum (SUB) in the hippocampus has been suggested on the basis of tracer studies, but this projection has not unequivocally been supported by physiological studies. The demonstration of such a functional pathway might be important to understand the functioning of the hippocampal memory system. Here we present physiological and further anatomical evidence for such a connection between PER and the hippocampus. Electrical stimulation of PER in vivo evoked field potentials (EFPs) at the border area of CA1/SUB, consisting of a short latency and a longer latency component. Current source density analysis revealed that the sink of the short latency component was situated in the molecular layer of area CA1/SUB, while the longer latency component had its sink in the outer molecular layer of the dentate gyrus (DG). Anterograde tracer injections in PER showed labelled fibres in the border area of CA1/SUB, but anatomical evidence for a projection of PER to DG was not found. When synaptic transmission in the entorhinal cortex was partly blocked, the amplitude of the longer latency component of the recorded EFPs in the hippocampus was decreased while the short latency component was not affected, which suggests that the indirect pathway originating in PER is mediated through a synaptic relay in the entorhinal cortex. From the present results we conclude that information originating in PER reaches area CA1/SUB by parallel, direct and indirect, routes. The existence of this parallel organization appears to form an essential feature for the proper function of the medial temporal lobe memory system.     

Expression of the integrin subunits alpha 5, alpha 6 and beta 1 in the testes of the common marmoset

Integrin subunits alpha 5, alpha 6 and beta 1 were localized in the testis of pre-pubertal or adult non-human primates (Callithrix jacchus) by immunofluorescence staining and in situ hybridization. In animals of all ages subunits alpha 5 and beta 1 were localized in cells of the lamina propria of the seminiferous epithelium. In prepubertal animals, the integrin subunits alpha 5, alpha 6, as well as beta 1, were distributed all over the plasma membrane of Sertoli cells. In adult animals the integrin subunits were confined to those plasma membrane regions of Sertoli cells which are assigned to the basal compartment, including the basement membrane of the seminiferous tubules. Protein expression of integrin subunits alpha 6 and beta 1 was most pronounced in tubular stages in which elongated spermatids were not yet present in the adluminal compartment of the epithelium, suggesting that these integrin subunits are particularly essential at certain developmental stages of spermatogenesis. Non-radioactive in situ hybridization revealed that the mRNA for integrin subunits alpha 5, alpha 6 and beta 1 was expressed by Sertoli cells. In situ hybridization, together with immunofluorescence data, shows that these integrin subunits were exclusively synthesized in Sertoli cells. As to functional aspects, it is concluded that during primate spermatogenesis. Sertoli cell integrins may be involved in both cell matrix as well as cell-cell interactions, particularly during early spermatogenesis.     

Proposal of a new electromechanical total artificial heart: the TAH Serpentina

A new type of energy converter for an electro-mechanical total artificial heart (TAH) based on the principle of a unidirectional moving motor is described. Named the TAH Serpentina, the concept consists of 2 major parts, a pendulum shaped movable element fixed on one side using a joint bearing and a special shaped drum cam. Pusher plates are mounted flexibly to the crossbar of the pendulum. A motor drives the special shaped drum cam linked to the pendulum through a ball bearing. The circular motion of the unidirectional moving brushless DC motor is transferred into the linear motion of the pendulum to drive the pusher plates. Using a crossbar with a variable length, the stroke of the pendulum and therefore the displaced blood volume is alterable. To achieve a variable length, an electric driven screw thread or a hydraulic system is possible. Comparable to the natural heart, cardiac output would be determined by frequency and stroke volume.     

Termination of extracorporeal membrane oxygenation for cardiac support

The determination of when to stop extracorporeal membrane oxygenation (ECMO) rests upon demonstration of the return of adequate cardiac function to support vital organs and permit subsequent recovery. In general, patients with myocardial stun will recover function within several days. Factors that limit recovery include elevated end diastolic pressures leading to marginal myocardial perfusion, ongoing organ damage, massive anasarca, or progressive deterioration in lung function. Following a trial of slow weaning of ECMO support to condition the heart to take over the entire system flow requirements, decannulation can be accomplished in a standard fashion. When weaning is not successful and additional time does not lead to adequate recovery of cardiac function, physicians and nurses must be prepare to realistically advise families regarding such options as cardiac transplantation or withdrawal of support. It is critically important to provide an open and nonjudgmental environment for families to make these difficult decisions. The greatest difficulties involve ethical and emotional decisions that need to be made in a timely fashion to prevent undo burden on the patient when further ECMO support is futile.     

Structure-activity relationships of quaternary protoberberine alkaloids having an antimalarial activity

Seventeen quaternary protoberberine alkaloids related to berberine 1 were tested for antimalarial activity in vitro against Plasmodium falciparum and structure-activity relationships are proposed. The activity of the protoberberine alkaloids was influenced by the type of the oxygen substituents on rings A, C and D and the position of the oxygen functions on ring D. The position of the oxygen functions on ring D and the type of the oxygen substituents at the C-13 position (ring C) strongly influenced the activity. Shifting the oxygen functions at C-9 and C-10 to C-10 and C-11 on ring D resulted in a significant increase in the activity. Compounds bearing a methylenedioxy function at C-2 and C-3 (ring A) or C-9 and C-10 (ring D) showed higher activity than those which have methoxy groups at the same positions. Introduction of a methoxy group into the C-1 position (ring A) decreased the activity. Replacement of a hydroxy group at C-2 or C-3 (ring A) by a methoxy group led to a reduction in the activity. Displacement of a hydroxy function at C-13 (ring C) by the oxygen substituents such as OMe, OEt, OCOOEt, and OCON(Me)₂ reduced the activity. In the same replacement at C-9 (ring D), the activity depended upon the type of the oxygen function. Six protoberberines displayed more potent activity than berberine 1. The activity decreased in the order: 10, 11, 17 and 18 > 7 and 8 > 1.