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91.
92.
Hendrik Bergsma Mark W. Konijnenberg Boen L. R. Kam Jaap J. M. Teunissen Peter P. Kooij Wouter W. de Herder Gaston J. H. Franssen Casper H. J. van Eijck Eric P. Krenning Dik J. Kwekkeboom 《European journal of nuclear medicine and molecular imaging》2016,43(3):453-463
Purpose
In peptide receptor radionuclide therapy (PRRT), the bone marrow (BM) is one of the dose-limiting organs. The accepted dose limit for BM is 2 Gy, adopted from 131I treatment. We investigated the incidence and duration of haematological toxicity and its risk factors in patients treated with PRRT with 177Lu-DOTA0-Tyr3-octreotate (177Lu-DOTATATE). Also, absorbed BM dose estimates were evaluated and compared with the accepted 2 Gy dose limit.Methods
The incidence and duration of grade 3 or 4 haematological toxicity (according to CTCAE v3.0) and risk factors were analysed. Mean BM dose per unit (gigabecquerels) of administered radioactivity was calculated and the correlations between doses to the BM and haematological risk factors were determined.Results
Haematological toxicity (grade 3/4) occurred in 34 (11 %) of 320 patients. In 15 of the 34 patients, this lasted more than 6 months or blood transfusions were required. Risk factors significantly associated with haematological toxicity were: poor renal function, white blood cell (WBC) count <4.0?×?109/l, age over 70 years, extensive tumour mass and high tumour uptake on the OctreoScan. Previous chemotherapy was not associated. The mean BM dose per administered activity in 23 evaluable patients was 67?±?7 mGy/GBq, resulting in a mean BM dose of 2 Gy in patients who received four cycles of 7.4 GBq 177Lu-DOTATATE. Significant correlations between (cumulative) BM dose and platelet and WBC counts were found in a selected group of patients.Conclusion
The incidence of subacute haematological toxicity after PRRT with 177Lu-DOTATATE is acceptable (11 %). Patients with impaired renal function, low WBC count, extensive tumour mass, high tumour uptake on the OctreoScan and/or advanced age are more likely to develop grade 3/4 haematological toxicity. The BM dose limit of 2 Gy, adopted from 131I, seems not to be valid for PRRT with 177Lu-DOTATATE.93.
94.
Groeneveld TW Ramwadhdoebé TH Trouw LA van den Ham DL van der Borden V Drijfhout JW Hiemstra PS Daha MR Roos A 《Molecular immunology》2007,44(14):3608-3614
Human neutrophil peptide-1 (HNP-1) is a member of the alpha-defensin family. Defensins are cationic antimicrobial peptides, which play an important role in the antimicrobial response to microorganisms. In addition, recent studies have revealed the involvement of defensins in inflammation, immunity and wound repair. Defensins are present in the azurophilic granules of neutrophils and are released upon neutrophil stimulation. Previous studies showed that HNP-1 binds to C1q and inhibits the classical complement pathway. In view of the structural and functional similarity between C1q and MBL, we have now examined the interactions between HNP-1 and MBL. We observed a dose-dependent binding of HNP-1 to MBL in calcium-free buffer, indicating that HNP-1 binds to MBL most likely via the collagenous domains. To identify the binding sites in HNP-1 involved in the binding to C1q and MBL, we used a series of overlapping synthetic linear peptides that spanned the entire HNP-1 sequence. Both MBL and C1q showed a dose-dependent binding to the same set of peptides, suggesting a similar binding site in HNP-1 for both MBL and C1q. Strongest binding was observed to peptides containing the C- or N-terminal part of the HNP-1 molecule. Using an ELISA based system, we demonstrated that HNP-1 inhibits activation of both the classical pathway and lectin pathway of complement. Furthermore, we demonstrated that C1q and MBL can form complexes with HNP-1 in solution. Together, the data indicate that HNP-1 interacts with both C1q and MBL efficiently resulting in inhibition of both the classical and the lectin pathway of complement. We conclude that HNP-1 may play a role in protection against tissue injury during inflammatory conditions by inhibiting the early phase of complement activation. 相似文献
95.
Soluble mannosylated myelin peptide inhibits the encephalitogenicity of autoreactive T cells during experimental autoimmune encephalomyelitis
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Kel J Oldenampsen J Luca M Drijfhout JW Koning F Nagelkerken L 《The American journal of pathology》2007,170(1):272-280
We have previously shown that immunization with a mannosylated myelin peptide in complete adjuvant induces tolerance instead of disease in experimental autoimmune encephalomyelitis (EAE), a rodent model for multiple sclerosis. In this report we demonstrate that treatment with a soluble mannosylated epitope of proteolipid protein (M-PLP(139-151)) significantly inhibits disease mediated by autoreactive myelin-specific T cells during EAE. Treatment with M-PLP(139-151), applied in different EAE models, significantly reduced the incidence of disease and the severity of clinical symptoms. Delayed-type hypersensitivity responses were abolished after peptide treatment, emphasizing the impact on peripheral T-cell reactivity. Histological analysis of spinal cord tissue from mice treated with M-PLP(139-151) revealed the presence of only few macrophages and T cells. Moreover, little expression of interferon-gamma, interleukin-23, or major histocompatibility complex class II antigen was detected. Immune modulation by M-PLP(139-151) was primarily antigen-specific because an irrelevant mannosylated peptide showed no significant effect on delayed-type hypersensitivity responses or on the course of EAE. Therefore, mannosylated antigens may represent a novel therapeutic approach for antigen-specific modulation of autoreactive T cells in vivo. 相似文献
96.
We used rapid serial visual presentation (RSVP) to examine the tuning of macaque inferior temporal cortical (IT) neurons to five sets of 25 shapes each that varied systematically along predefined shape dimensions. A comparison of the RSVP technique using 100-ms presentations with that using a longer duration showed that shape preference can be determined with RSVP. Using relatively complex shapes that vary along relatively simple shape dimensions, we found that the large majority of neurons preferred extremes of the shape configuration, extending the results of a previous study using simpler shapes and a standard testing paradigm. A population analysis of the neuronal responses demonstrated that, in general, IT neurons can represent the similarities among the shapes at an ordinal level, extending a previous study that used a smaller number of shapes and a categorization task. However, the same analysis showed that IT neurons do not faithfully represent the physical similarities among the shapes. The responses to the two-part shapes could be predicted, virtually perfectly, from the average of the responses to the respective two parts presented in isolation. We also showed that IT neurons adapt to the stimulus distribution statistics. The neural shape discrimination improved when a shape set with a narrower stimulus range was presented, suggesting that the tuning of IT neurons is not static but adapts to the stimulus distribution statistics, at least when stimulated at a high rate with a restricted set of stimuli. 相似文献
97.
Wanders RJ Visser WF van Roermund CW Kemp S Waterham HR 《Pflügers Archiv : European journal of physiology》2007,453(5):719-734
This review describes the current state of knowledge about the ABCD family of peroxisomal half adenosine-triphosphate-binding
cassette (ABC) transporters. ABCDs are predicted to be present in a variety of eukaryotic organisms, although at present,
only ABCDs in the yeast Saccharomyces cerevisiae, the plant Arabidopsis thaliana, and different mammalian species have been identified and characterized to any significant extent. The functional role of
none of these ABCDs has been established definitively and awaits successful reconstitution of ABCDs, either as homo- or heterodimers
into liposomes, followed by transport studies. Data obtained in S. cerevisiae suggest that the two ABCDs, which have been identified in this organism, form a heterodimer, which actually transports acyl
coenzyme A esters across the peroxisomal membrane. In mammals, four ABCDs have been identified, of which one [adrenoleukodystrophy
protein (ALDP)] has been implicated in the transport of the coenzyme A esters of very-long-chain fatty acids. Mutations in
the gene (ABCD1) encoding ALDP are the cause of a severe X-linked disease, called X-linked adrenoleukodystrophy. The availability of mutant
mice in which Abcd1, Abcd2, or Abcd3 have been disrupted will help to resolve the true role of the peroxisomal half-ABC transporters. 相似文献
98.
Sevak RJ Koek W Galli A France CP 《The Journal of pharmacology and experimental therapeutics》2007,320(3):1216-1223
Streptozotocin (STZ)-induced diabetes can modulate dopamine (DA) neurotransmission and thereby modify the behavioral effects of drugs acting on DA systems. Insulin replacement, and in some conditions repeated treatment with amphetamine, can partially restore sensitivity of STZ-treated rats to dopaminergic drugs. The present study sought to characterize the role of insulin and amphetamine in modulating the behavioral effects of drugs that selectively act on D2/D3 receptors. In control rats, quinpirole and quinelorane produced yawning, whereas raclopride and gamma-hydroxybutyric acid (GHB) produced catalepsy. Raclopride antagonized quinpirole- and quinelorane-induced yawning with similar potency. STZ treatment increased blood glucose concentration, decreased body weight, and markedly reduced sensitivity to quinpirole-induced yawning, quinelorane-induced yawning as well as to raclopride-induced catalepsy, while enhancing sensitivity to GHB-induced catalepsy. Repeated treatment with amphetamine partially restored sensitivity of STZ-treated rats to amphetamine-stimulated locomotion and also produced conditioned place preference, without affecting blood glucose and body weight changes. However, amphetamine treatment did not restore sensitivity to the behavioral effects of quinpirole, raclopride, or GHB, suggesting differential regulation of dopamine transporter activity and sensitivity of D2 receptors in hypoinsulinemic rats. Insulin replacement in STZ-treated rats normalized blood glucose and body weight changes and fully restored sensitivity to quinpirole-induced yawning, as well as to raclopride-induced catalepsy, while reducing sensitivity to GHB-induced catalepsy. Overall, these data indicate that changes in insulin status markedly affect sensitivity to the behavioral effects of dopaminergic drugs. The results underscore the importance of insulin in modulating DA neurotransmission; these effects might be especially relevant to understanding the co-morbidity of eating disorders and substance abuse. 相似文献
99.
Mathieu D'Hondt Hans Pottel Dirk Devriendt Frank Van Rooy Franky Vansteenkiste Barbara Van Ooteghem Wouter De Corte 《JSLS, Journal of the Society of Laparoendoscopic Surgeons》2014,18(3)
Background and Objectives:
In this single-institution study, we aimed to compare the safety, feasibility, and outcomes of single-incision laparoscopic sigmoidectomy (SILSS) with multiport laparoscopic sigmoidectomy (MLS) for recurrent diverticulitis.Methods:
Between October 2011 and February 2013, 60 sigmoidectomies were performed by the same surgeon. Forty patients had a MLS and 20 patients had a SILSS. Outcomes were compared.Results:
Patient characteristics were similar. There was no difference in morbidity, mortality or readmission rates. The mean operative time was longer in the SILSS group (P = .0012). In a larger proportion of patients from the SILSS group, 2 linear staplers were needed for transection at the rectum (P = .006). The total cost of disposable items was higher in the SILSS group (P < .0001). No additional ports were placed in the SILSS group. Return to bowel function or return to oral intake was faster in the SILSS group (P = .0446 and P = .0137, respectively). Maximum pain scores on postoperative days 1 and 2 were significantly less for the SILSS group (P = .0014 and P = .047, respectively). Hospital stay was borderline statistically shorter in the SILSS group (P = .0053). SILSS was also associated with better cosmesis (P < .0011).Conclusion:
SILSS is feasible and safe and is associated with earlier recovery of bowel function, a significant reduction in postoperative pain, and better cosmesis. 相似文献100.
Wouter H. Mallee Job N. Doornberg David Ring Mario Maas Maaike Muhl C. Niek van Dijk J. Carel Goslings 《Hand (New York, N.Y.)》2014,9(1):117-121