Defective Treg response in acute kidney injury was caused by a reduction in TIM-3+ Treg cells

Background: Despite years of research, the treatment of acute kidney injury (AKI) remains a significant challenge. Animal studies presented causal links between elevated regulatory T cell (Treg) response and better prognosis in AKI. Previous studies in mice and humans showed that TIM-3+ Treg cells were more potent than TIM-3- Treg cells. In this study, we investigated the role of TIM-3 in Treg in AKI patients.

Methods: Peripheral blood from AKI patients and healthy controls were gathered, and TIM-3+ Treg subset was examined.

Results: Compared to healthy controls, the AKI patients presented a significant upregulation in the frequency of circulating CD4+CD25+ T cells; however, the majority of this increase was from the CD4+CD25+TIM-3- subset, and the frequency of CD4+CD25+TIM-3+ T cells was downregulated in AKI patients. In both healthy controls and AKI patients, the CD4+CD25+TIM-3+ T cells expressed higher levels of Foxp3, and were more potent at expressing LFA-1, LAG-3, CTLA-4, IL-10 and TGF-β. In addition, the CD4+CD25+TIM-3+ T cells from both healthy controls and AKI patients presented higher capacity to suppress CD4+CD25- T cell proliferation than the CD4+CD25+TIM-3- T cells. Interestingly, the total CD4+CD25+ T cells from AKI patients presented significantly lower inhibitory capacity than those from healthy controls, indicating that the low frequency of CD4+CD25+TIM-3+ T cells was restricting the efficacy of the Treg responses in AKI patients.

Conclusions: We demonstrated that TIM-3 downregulation impaired the function of Treg cells in AKI. The therapeutic potential of CD4+CD25+TIM-3+ T cells in AKI should be investigated in future studies.     

Pneumonien bei akuten Leukämien

Summary Acute leukaemia was complicated by pneumonia in 38 (34.8%) of 109 patients treated between 1979 and 1983; in 39.5% of the patients pneumonia occurred more than once. In 23 patients (60.5%) pneumonia occurred during cytostatic therapy, and 25 patients (65.8%) had less than 1000 mm² granulocytes. Antibiotic therapy had no or only little effect in 70%. A total of 21 patients (55.3%) died of pneumonia. In 15 patients a direct relationship could be seen between pneumonia and the bacterial spectrum in the sputum. A prevalence of gram-negative bacteria was found (24 of 40 bacteria isolated, especially Enterobacteriaceae (19). Fungi were cultivated in 10 cases. Each of the typical pneumonia bacteria was only seen once respectively. It is most important that therapy begin immediately, even before the bacteria have been identified. Only then is there hope that the survival time of patients with acute leukaemia can be influenced.

     

Membrane attack complex of complement and 20 kDa homologous restriction factor (CD59) in myocardial infarction

In order to investigate the mechanism of deposition of the complement membrane attack complex (MAC) in cardiomyocytes in areas of human myocardial infarction, the 20 kDA homologous restriction factor of complement (HRF20; CD59) and complement components (C1q, C3d and MAC) were analysed immunohistochemically using specific antibodies. Myocardial tissues obtained at autopsy from nine patients who died of acute myocardial infarction were fixed in acetone and embedded in paraffin. The ages of the infarcts ranged from about 3.5 h to 12 days. In cases of myocardial infarction of 20 h or less, MAC deposition was shown in the infarcted cardiomyocytes without loss of HRF20. Where the duration was 4 days or more, the cardiomyocytes with MAC deposition in the infarcted areas also showed complete loss of HRF20. Outside the infarcts, HRF20 in the cardiomyocytes was well preserved without MAC deposition. The present study suggests that the initial MAC deposition in dead cardiomyocytes can occur as a result of degradation of plasma-membrane by a mechanism independent of complement-mediated injury to the membrane. Loss of HRF20 from dead cardiomyocytes may not be the initial cause of MAC deposition, but may accelerate the deposition process of MAC in later stages of infarction.     

HLA antigens, psoriasis and acute anterior uveitis in Bechterew's syndrome (ankylosing spondylitis)

One hundred and twenty-two consecutively hospitalized patients with ankylosing spondylitis (AS) were reexamined. Ninety-two per cent were HLA B27 positive. Of the HLA B27 negative patients, 60% were found to have psoriasis, as opposed to 11 % of the HLA B27 positive patients. Acute anterior uveitis (AAU) was found only in HLA B27 positive patients, and more frequently in males than in females. The genetic and clinical heterogeneity of AS, together with the overlapping clinical criteria for AS and psoriatic spondylitis, may make the term "Bechterew's syndrome" preferable. Based on these findings and previous reports, we conclude that (i) AAU is a manifestation of Bechterew's syndrome in HLA B27 positive patients, (ii) HLA B27 negative patients without any obvious accompanying manifestations may suffer from psoriatic spondylitis, and (iii) genetic predisposition to psoriasis in persons who are HLA B13, B17 and B37 negative, may interact with the genetic predisposition to Bechterew's syndrome in HLA B27 positive persons and produce Bechterew's syndrome with psoriasis or psoriasis-like skin eruptions.     

Urodilatin: a new peptide with beneficial effects in the postoperative therapy of cardiac transplant recipients

Summary Renal failure after heart transplantation (HTx) still remains a serious problem, especially when cyclosporin A is used for immunosuppression in the early postoperative therapy. To preserve good renal function without reducing immunosuppressive cyclosporin A treatment, we administered urodilatin (CDD/ANP-95-126) in a long-term, low-dose infusion in addition to the usual medication after heart transplantation. From November 1990 to June 1991, 51 patients (46 male and 5 female; mean age 48 years) were treated with a 620 ng/kg bw·min infusion for 96 h after HTx. The renal function and hemodynamic parameters of these urodilatin-treated patients were compared in this sequential study with 40 patients (33 male and 7 female; mean age 49 years) who had undergone HTx previously from May to November, 1990, as controls. In this phase IIa study, both groups did not differ significantly with respect to age, sex, indication for HTx, and preoperative renal function. In comparison with controls patients treated with urodilatin had a significantly better renal function: a reduction in the peak plasma creatinine (PC values day 4 : 1.5 ± 0.11 vs. 2.19 ± 0.19 mg/dl; P = 0.002), a lower peak serum urea (SU values day 4 : 109 ± 8 vs. 154.7 ± 8.94 mg/dl ; P = 0.0036), and a lower incidence of hemodialysis (6% vs. 10%) were observed. Adequate diuresis was maintained in spite of the reduction of furosemide by more than 60% (P = 0.005) on each day of urodilatin infusion in comparison with controls. The mean central venous pressure was significantly lower by about 50% (P = 0.02) during the administration of urodilatin in spite of reduced vasodilator medication with nitroglycerin. From this phase IIa study, we may conclude that urodilatin could be an important drug in intensive care treatment. For patients undergoing HTx, this peptide seems to be indicated for the improvement of renal function and cardiovascular status, especially in postoperative therapy using high-dose cyclosporin A treatment.Abbreviations ACE angiotensin converting enzyme - ANP atrial natriuretic polypeptide - ATG antithymocyte globulin - bpm beats per minute - bw body weight - CDD cardiodilatin - CDD/ANP-99-126 circulating form of vasorelaxant cardiac peptide - CHD coronary heart disease - CyA cyclosporin A - DCM dilated cardiomyopathy - GLM general linear model - hANP human atrial natriuretic polypeptide - HTx heart transplantation - NTG nitroglycerine - PC plasma creatinine - SU serum urea - SAS statistical analysing system     

The response of heat shock proteins 25 and 72 to ischaemia in different kidney zones

 Induction of heat shock proteins (HSPs) following cell injury contributes to the protection of vital cell functions. It was, therefore, of interest to study the effects of transient renal ischaemia on the abundance and distribution of two HSPs, HSP25 and HSP72, in renal tissue using Western-blot techniques. Analyses were performed on the supernatant (HSP25, HSP72) and pellet (HSP25) of homogenates obtained from cortex (CX) and outer (OM) and inner (IM) medulla of the rat kidney immediately after 60 min of ischaemia followed by varying periods of reperfusion. Ischaemia of the left kidney caused HSP25 contents to decrease in CX, OM and IM by 73, 89 and 54% respectively, compared with the corresponding zones of the contralateral control kidney. This initial decrease in supernatant HSP25 was accompanied by an increased abundance of HSP25 in the pellet. Following reperfusion, HSP25 contents in the supernatant gradually increased in CX and OM, reaching, after 24 h, values that were 5.4- and 2.5-fold higher, respectively, than those in the control kidneys. After 7 or 14 days of reperfusion, HSP25 contents had not completely normalised in CX, but had reached control levels in OM. In IM, the HSP25 content remained below control throughout the entire reperfusion period. HSP72 (supernatant) was below the detection limit in the CX of the control kidney. Similar to the level of HSP25, that of HSP72 was also markedly lower in OM and IM immediately after ischaemia. The intrarenal distribution of HSP72 and the sequence of zonal changes in HSP72 contents were similar to those observed for HSP25. These results are compatible with the view that, during ischaemia and the initial reperfusion period, HSP25 migrates from the cytoplasmic compartment (supernatant) into the nucleus and/or associates with cytoskeletal structures. The observation that both HSP25 and HSP72 are transiently induced in CX and OM, but not in IM, may be explained by the fact that, while all kidney cells are exposed to ischaemic stress, only inner medullary cells experience a major postischaemic attenuation of osmotic stress. Received: 11 February 1997 / Received after revision and accepted: 26 March 1997     

Surgical treatment of acute subdural hygroma in children

During the years 1967–1984, 91 children were operated on because of acute compressive traumatic intracranial hematoma; 16 (17%) had traumatic acute subdural hygromas. These were unilateral in 12 cases and bilateral in 4. The causes of injury were traffic accidents in 11 children, a fall in 1, and acute deceleration injuries in 5. Nine children suffered multiple injuries to the thorax, inferior extremities, and pelvis. Clinical manifestations and evolution of clinical symptoms included changes in conscious level, palsy, high fever, nystagmus, maximum dilation of either pupil and spontaneous, irregular breathing. The diagnosis was made on the basis of the clinical picture and supplementary clinical investigations: CT, EEG, echoencephalography, isotope cisternography, and arteriography. Treatment was by simple trephination of the cranium and evacuation of hygromatous liquid. All children survived the surgical treatment; 1 child died after the operation and 2 developed hydrocephalus.     

Acute renal failure in diabetics

Conclusions Acute renal failure in diabetic patients occurs, as a result of certain specific conditions. The most common of these are hyperglycaemic hyperosmolar coma, diabetic ketoacidosis, the use of radiocontrast media, and renal papillary necrosis. The management of diabetics with acute renal failure is essentially the same as for non-diabetic patients but may be complicated by the problems of metabolic control, vascular access, and vascular instability. Prevention is important as the development of acute renal failure adds considerably to the morbidity and mortality of these conditions and is often avoidable.Wellcome Research Fellow     

急性心肌梗塞Q－T离散度分析－－附68例临床报告

目的：探讨急性心肌梗塞（AMI）患首次心电图Q－T离散度（Q－Td)及Q－Tc离散度（Q－Tcd）与严重室性心律失常发生的关系,对预后进行评估。方法：对68例AMI患首次心电图Q－Td及Q－Tcd进行测定。结果：18例AMI并室速室颤组患Q－Td,Q－Tcd显高于50例非室速室颤组患;结论：AMI患Q－Td及Q－Tcd值增大,室速室颤发生率增加,两呈正相关关系,易发生心源性猝死。故Q－Td及Q－Tcd可作为AMI病情危重预后差的标志,对判断预后有重要临床意义。