Engraftment of dogs with Ia-positive marrow cells isolated by avidin- biotin immunoadsorption

Previous work has shown failure of engraftment in lethally irradiated dogs when autologous marrow was depleted of Ia-positive cells with an anti-Ia antibody and complement before infusion. In the current study, we have utilized an avidin-biotin immunoadsorption procedure to obtain a population of highly enriched Ia-positive cells for autologous bone marrow transplantation in dogs given lethal irradiation. Dog marrow cells (2.4 to 7.0 X 10(9) cells) that contained 8.6% to 19.9% Ia- positive cells were treated successively with monoclonal antibody 7.2, which reacts with a framework determinant of Ia-antigen, and biotin- conjugated goat antimouse immunoglobulin. These treated cells were passed over a column of avidin-Biogel (polyacrylamide) and the adherent cells removed by mechanical agitation. Seven lethally irradiated dogs were transplanted with 5.9 to 33.4 X 10(6) recovered adherent cells per kilogram of which 69.0% to 88.0% were Ia-positive. All dogs had hematologic recovery; six are alive and well with durable engraftment and one died on day 15 posttransplant. They are immunologically normal as determined by lymph node and bone marrow biopsies, lymphocyte function, and immunophenotyping of peripheral blood and bone marrow cells. These data provide further evidence that canine hematopoietic stem cells express Ia-like antigens and that these cells are capable of complete hematopoietic and immunologic reconstitution in an autologous model.     

Factors associated with poor outcomes in patients with lupus nephritis

The objective of this study was to identify the factors associated with important clinical outcomes in a case-control study of 213 patients with lupus nephritis. Included were 47% Hispanics, 44% African Americans and 9% Caucasians with a mean age of 28 years. Fifty-four (25%) patients reached the primary composite outcome of doubling serum creatinine, end-stage renal disease or death during a mean follow-up of 37 months. Thirty-four percent African Americans, 20% Hispanics and 10% Caucasians reached the primary composite outcome (P < 0.05). Patients reaching the composite outcome had predominantly proliferative lupus nephritis (WHO classes: 30% III, 32% IV, 18% V and 5% II, P < 0.025) with higher activity index score (7 +/- 6 versus 5 +/- 5, P < 0.05), chronicity index (CI) score (4 +/- 3 versus 2 +/- 2 unit, P < 0.025), higher baseline mean arterial pressure (MAP) (111 +/- 21 versus 102 +/- 14 mmHg, P < 0.025) and serum creatinine (1.9 +/- 1.3 versus 1.3 +/- 1.0 mg/dL, P < 0.025), but lower baseline hematocrit (29 +/- 6 versus 31 + 5%, P < 0.025) and complement C3 (54 +/- 26 versus 65 + 33 mg/dL, P < 0.025) compared to controls. More patients reaching the composite outcome had nephrotic range proteinuria compared to controls (74% versus 56%, P < 0.025). By multivariate analysis, CI (hazard ratio [95% CI] 1.18 [1.07-1.30] per point), MAP (HR 1.02 [1.00-1.03] per mmHg), and baseline serum creatinine (HR 1.26 [1.04-1.54] per mg/dL) were independently associated with the composite outcome. We concluded that hypertension and elevated serum creatinine at the time of the kidney biopsy as well as a high CI are associated with an increased the risk for chronic renal failure or death in patients with lupus nephritis.     

WONCA研究论文摘要汇编——基层抑郁症风险患者的连续性服务

背景目前已开展了对重性精神病患者进提供连续性服务的研究。目的探讨基层对有抑郁症风险患者提供连续性服务的水平,并与对心力衰竭患者的服务水平进行对比。方法采用抑郁症风险患者与心力衰竭患者对比的探索性研究。采用患者问卷评估服务的持续性,包含如下内容:(1)联系的服务提供者数(个人连续性);(2)诊所内服务提供者之间的合作(团队连续性)(6个项目,分数1~5分);(3)诊所外全科医师与服务提供者之间的合作(跨界连续性)(4个项目,分数1~5分)。结果大多数抑郁症风险患者在过去1年中寻遍整个服务提供界联系了几个服务提供者,曾遇到过高水平团队连续性服务及低水平跨界连续性服务。在诊所中可接触到的不同服务提供者要明显多于心力衰竭患者服务提供者(P<0.01)。抑郁症风险患者的服务提供者之间的合作更好一些,每项平均得分4.3分,心力衰竭患者得分为4.0分(P=0.03)。然而,跨界连续性服务方面正好相反:抑郁症风险患者每项平均得分3.5分,心力衰竭患者得分为4.0分(P=0.01)。结论抑郁症风险患者与心力衰竭患者之间的探索性对比显示:体验服务连续性方面的差距不大。对此还应行进一步分析。     

Enhanced Dopamine-Dependent Hippocampal Plasticity after Single MK-801 Application

Dopaminergic hyperfunction and N-methyl-D-aspartate receptor (NMDAR) hypofunction have both been implicated in psychosis. Dopamine-releasing drugs and NMDAR antagonists replicate symptoms associated with psychosis in healthy humans and exacerbate symptoms in patients with schizophrenia. Though hippocampal dysfunction contributes to psychosis, the impact of NMDAR hypofunction on hippocampal plasticity remains poorly understood. Here, we used an NMDAR antagonist rodent model of psychosis to investigate hippocampal long-term potentiation (LTP). We found that single systemic NMDAR antagonism results in a region-specific, presynaptic LTP at hippocampal CA1-subiculum synapses that is induced by activation of D1/D5 dopamine receptors and modulated by L-type voltage-gated Ca²⁺ channels. Thereby, our findings may provide a cellular mechanism how NMDAR antagonism can lead to an enhanced hippocampal output causing activation of the hippocampus-ventral tegmental area-loop and overdrive of the dopamine system.     

Empfehlungen zur Prognosebeurteilung bei cerebraler Hypoxie nach kardiopulmonaler Reanimation ?sterreichische interdisziplin?re Konsensuskonferenz ?sterreichische interdisziplin?re Konsensuskonferenz

In den letzten Jahren wurden zahlreiche Prognoseparameter zur Beurteilung der cerebralen Hypoxie nach kardiopulmonaler Reanimation untersucht. Diese Parameter umfassen neben klinischen Daten und klinischen Scoresystemen, verschiedene klinisch-neurologische Befunde, biochemische Parameter, elektrophysiologische Untersuchungen und neurodiagnostische bildgebende Verfahren.    Ziel der ?sterreichischen interdisziplin?ren Konsensuskonferenz war die kritische Evaluierung dieser Parameter und die Empfehlung welche Parameter bzw. diagnostischen Ma?nahmen zu welchem Zeitpunkt eine prognostische Aussage über eine potentielle neurologische Rehabilitation nach cerebraler Hypoxie erm?glichen. Aus mehr als 100 unterschiedlichen Parametern wurden 26 Parameter identifiziert, die, basierend auf Ergebnisse wissenschaftlicher Publikationen, eine prognostische Aussage erm?glichen. Diese Parameter müssen jedoch hinsichtlich der Einsch?tzung der Evidenz und deren St?rkegrad als Grundlage für prognostische Empfehlungen unterschiedlich beurteilt werden.     

Rickettsial and serologic evidence for prevalent spotted fever rickettsiosis in inner Mongolia

A field study in northeastern Inner Mongolia, People's Republic of China, in June of 1985 demonstrated a spotted fever group rickettsiosis. Two strains of spotted fever group rickettsiae were isolated. One strain was obtained from the blood of a patient with an eschar, regional lymphadenopathy, and history of a recent tick bite. The other strain originated from ova of ticks, Dermacentor nuttalli. These represent the second isolate of a spotted fever group rickettsia from a human and the first isolate from tick ova in the People's Republic of China. Antibodies to these rickettsiae were demonstrated by indirect immunofluorescence in the sera of 4% of healthy children and 34% of healthy human adults, in 58% of sheep, and in 76% of cattle in the same location. Hemolymph test revealed rickettsiae in 6 of 36 D. nuttalli examined.     

Joint biomarkers in idiopathic femoral head osteonecrosis: comparison with hip osteoarthritis

OBJECTIVE: To compare concentrations of joint biomarkers in synovial fluid (SF) between idiopathic osteonecrosis of the femoral head (ION) and osteoarthritis (OA) of the hip joint. METHODS: Levels of the joint biomarkers cartilage oligomeric matrix protein (COMP), antigenic keratan sulfate (AgKS), and hyaluronan (HA) in SF samples from 21 cases of ION and their relationship to disease stage and history of steroid use were assessed and compared to the result of 29 cases of hip OA. RESULTS: In both the ION and hip OA groups, levels of COMP and AgKS in SF showed a significant positive correlation. The ION group had significantly higher levels of AgKS in SF than the hip OA group. In the ION group, stage II patients had significantly higher SF levels of both COMP and AgKS than those in stage III patients. No difference in level of HA in hip joint SF was found between steroid and non-steroid treated ION patients or between the stage II and III subgroups. CONCLUSION: SF levels of COMP and AgKS may serve as useful joint biomarkers that reflect cartilage metabolism not only in hip OA but also in ION.     

Interactions of aromatic amino acids with gastric secretagogues in humans

To determine the interactions of phenylalanine and tryptophan with gastric secretagogues, acid secretory studies were performed in 10 healthy subjects. Phenylalanine and tryptophan potentiated the gastric secretory responses following low doses of pentagastrin, whereas their effects on acid secretion stimulated by low doses of histamine or the cholinergic bethanecol were additive. Phenylalanine and tryptophan did not increase maximal acid output stimulated by pentagastrin, histamine, or bethanecol. Doses of the H2-receptor antagonist ranitidine, the prostaglandin E1 analogue misoprostol, atropine, and somatostatin that produced approximately 50% inhibition of pentagastrin-stimulated acid secretion significantly inhibited phenylalanine- and tryptophan-stimulated acid secretion. After the combination of either phenylalanine or tryptophan with pentagastrin, the H2-receptor antagonist significantly inhibited gastric acid secretion, whereas somatostatin, atropine, and the prostaglandin E1 analogue were not effective. These results indicate that both phenylalanine and tryptophan potentiate gastric acid secretion stimulated by a submaximal dose of pentagastrin, whereas their effects on histamine- and bethanecol-stimulated secretion are additive. The potentiating effects of phenylalanine and tryptophan on pentagastrin-stimulated acid secretion depend, at least in part, on intact histamine pathways.     

Coincidence of familial platelet glycoprotein Ib/IX deficiency (Bernard-Soulier syndrome), idiopathic autoantibody against platelet glycoprotein Ib/IX,familial appearence of antiphospholipid antibodies,and familial factor XII deficiency

Summary The case of an 8-year-old boy with apparently homozygous Bernard-Soulier syndrome (platelet GP Ib/IX complex deficiency) and a transient idiopathic autoantibody against GP Ib/IX is described. He had been diagnosed with chronic autoimmune thrombocytopenia (due to the detection of antiplatelet autoantibodies) before Bernard-Soulier syndrome was proven. Both parents and his brother displayed intermediate deficiency of GP Ib/IX, thus indicating a heterozygote state for Bernard-Soulier syndrome. Alloimmunization as an explanation for the appearance of GP Ib/IX antiplatelet antibodies in the propositus can be excluded. A so-called pseudo Bernard-Soulier syndrome due to selective antibodies was also excluded. Flow cytometric analysis revealed residual expression of 2% GP Ib and 13% GP IX on the propositus' platelets. It seems that the propositus showed an idiopathic autoantibody against a platelet glycoprotein in which he is genetically deficient (but which is not completely lacking). Thus, in patients with untypical behavior upon therapy of autoimmune thrombocytopenia, other differential diagnoses should also be considered even if antiplatelet antibodies are detected. In addition, all family members displayed elevated concentrations of antiphospholipid antibodies. These findings raise the question of a genetic predisposition for the development of autoantibodies. Moreover, an F. XII deficiency was found in all family members except the mother.