New Types of Germacranolides from Austroliabum candidum1.

The investigation of AUSTROLIABUM CANDIDUM afforded, in addition to several known sesquiterpene lactones, four new ones, including three germacranolides with an ether bridge, as well as an unusual glucoside. The structures were elucidated by spectroscopic methods.     

Plasma serine in schizophrenics and controls measured by gas chromatography-mass spectrometry.

In several previous studies, we reported significantly higher plasma serine concentrations in psychotic (and schizophrenic) subjects compared with nonpsychotic and control subjects. In those studies, we used a gas chromatography technique to assay the amino acids. Perry and Hanson (1985), using cation-exchange chromatography to assay plasma amino acids, found no differences in the plasma serine concentrations of controls compared with schizophrenic patients. They criticized our work on technical grounds and suggested that some other substance was co-eluting with the gas chromatographic serine peaks in our assays. We have now examined the plasma of schizophrenic and control subjects with gas chromatography-mass spectrometry (GC-MS), where accurate amino acid quantitation relative to a known internal standard can be achieved. The results show that the plasma serine concentrations of schizophrenic patients are significantly higher than those of controls. Also, plasma glycine concentrations are significantly higher in schizophrenic patients compared with controls.     

Interaction of polystyryl radical with copper(II) complexes

The polymerization of styrene initiated by 2,2′-azoisobutyronitrile (AIBN) was studied in N,N-dimethylformamide (DMF) solution at 60°C in the presence of tetrakis(N,N-dimethylformamide)copper(II) perchlorate, and also in the presence of its monoazido copper(II) complex [Cu(DMF)₃N₃]⁺. The monoazido complex in DMF was prepared in situ by mixing solid sodium azide with tetrakis(N,N-dimethylformamide)copper(II) perchlorate in a mole ratio of 1:1. The nature of the complex was established by Job's method. The equilibrium constant K for the reaction [Cu(DMF)₄]²⁺ + N ? [Cu(DMF)₃N₃]⁺ + DMF determined by the limiting logarithmic method was found to be 1,25 · 10⁴l · mol^?1. The presence of [Cu(DMF)₄]²⁺ ions in the polymerization systems caused retardation, but [Cu(DMF)₃N₃]⁺ ions produced well defined induction periods. The rate constants at 60°C for the interaction of polystyryl radical towards [Cu(DMF)₄]²⁺ and [Cu(DMF)₃N₃]⁺ ions were calculated to be 6,6 · 10² and 5,74 · 10⁴ l · mol^?1 · s^?1, respectively.     

Requirement of HMGB1 and RAGE for the maturation of human plasmacytoid dendritic cells

Dendritic cells (DC) are key components of innate and adaptive immune responses. Plasmacytoid DC (PDC) are a specialized DC subset that produce high amounts of type I interferons in response to microbes. High mobility group box 1 protein (HMGB1) is an abundant nuclear protein, which acts as a potent pro-inflammatory factor when released extracellularly. We show that HMGB1 leaves the nucleus of maturing PDC following TLR9 activation, and that PDC express on the plasma membrane the best-characterized receptor for HMGB1, RAGE. Maturation and type I IFN secretion of PDC is hindered when the HMGB1/RAGE pathway is disrupted. These results reveal HMGB1 and RAGE as the first known autocrine loop modulating the maturation of PDC, and suggest that antagonists of HMGB1/RAGE might have therapeutic potential for the treatment of systemic human diseases.     

Irritability following traumatic brain injury

This study was undertaken to identify the clinical and pathoanatomical correlates of irritability in patients with closed head injuries. A consecutive series of 66 patients was assessed in hospital and at 3, 6, 9, and 12-month follow-ups. Patients fulfilling criteria for irritability were divided into 2 groups based on the immediate or delayed onset of their irritability and compared with patients without irritability for background characteristics, impairment variables, and lesion characteristics. There were 12 patients (18.2%) with acute onset irritability and 10 (15.1%) with delayed onset irritability. Acute onset irritability patients had a higher frequency of left cortical lesions. Delayed onset irritability patients showed a strong association with poor social functioning and greater impairment in activities of daily living. The findings suggest that post-brain injury irritability may have different causes and treatment in the acute and chronic stages.     

Neoplastic and non‐neoplastic complications of solid organ transplantation in patients with preexisting monoclonal gammopathy of undetermined significance

Monoclonal gammopathy of undetermined significance (MGUS) occurs in 3–7% of the elderly population, with higher prevalence in renal failure patients, and is associated with a 25‐fold increased lifetime risk for plasma cell myeloma (PCM), also known as multiple myeloma. Using the California State Inpatient, Emergency Department, and Ambulatory Surgery Databases components of the Healthcare Cost and Utilization Project (HCUP), we sought to determine whether patients with MGUS who undergo solid organ allograft (n = 22 062) are at increased adjusted relative risk (aRR) for hematologic malignancy and other complications. Among solid organ transplant patients, patients with preexisting MGUS had higher aRR of PCM (aRR 19.46; 95% CI 7.05, 53.73; p < 0.001), venous thromboembolic events (aRR 1.66; 95% CI 1.15, 2.41; p = 0.007), and infection (aRR 1.24; 95% CI 1.06, 1.45; p = 0.007). However, when comparing MGUS patients with and without solid organ transplant, there was decreased aRR for PCM with transplant (aRR 0.34; 95% CI 0.13, 0.88; p = 0.027), and increased venous thromboembolic events (aRR 2.33; 95% CI 1.58, 3.44; p < 0.001) and infectious risks (aRR 1.44; 95% CI 1.23, 1.70; p < 0.001). While MGUS increased the risk of PCM overall following solid organ transplantation, there was lower risk of PCM development compared to MGUS patients who did not receive a transplant. MGUS should not preclude solid organ transplant.