The RBE of Gamma-rays and Fission Neutrons for Acute and Sub-acute Effects in Irradiated Rabbits

Summary

Rabbits were given acute whole-body irradiation with either neutrons (mean energy 0·7 mev, dose range 400–1500 rads) or gamma-rays (mean energy 2·5 mev, dose range 1000–3000 R). The last acute death was at 32 days and the LD50/32 was 572 rads for neutrons and 1389 R for gamma-rays, giving an RBE of 2·4.

Acute deaths were primarily due to haemopoietic failure, but damage to the alimentary tract probably also played a part. Coprophagia (re-ingestion), which is normal in rabbits, may have increased the liability to post-irradiation infection.

Sub-acute lesions, between 2 and 7 months after irradiation, occurred only after exposure to neutrons and not after gamma-rays. Just over half were local lesions of limbs, related to the entry dose of neutrons, and the remainder were intrathoracic effusions. When these sub-acute effects were taken into account the RBE rose to 3·0.     

Cyclic neutropenia (CN): a clue to the control of granulopoiesis

A simple quantitative feedback model of granulopoiesis is presented and discussed within the framework of existing data on granulopoiesis in both normals and patients with cyclic neutropenia (CN). The model assumes that the controlled compartment is the bone marrow pool of mature neutrophils (PMNs), which sends a negative feedback signal to the mitotic pool of early granulocyte precursors (i.e., CFU-C, myeloblasts, etc.) thus controlling the granulocyte production rate. Three parameters are found to play important roles in determining the response of the system to perturbations. These are: TM, the granulocyte maturation time; a, a parameter reflecting the strength of the negative feedback exerted by mature PMNs on the granulocyte production rate; and b, a parameter describing the leakiness of the bone marrow for PMN egress. It is shown that depending on the relative magnitudes of a and b, the system will either respond to perturbations with a damped oscillation (a less than b: the normal state) or with a sustained oscillation (a greater than b: the CN state). In both cases, the oscillation period is found to approximately equal 2TM. Deductions of the values of a, b, and TM from experimental data are consistent with the predictions of the model and show an increased value of a in CN relative to the normal state. This suggests an overly active feedback mechanism as the pathophysiologic basis of CN. In addition, the model can explain how various therapeutic agent correct CN and also provides insight into why other hematologic cell lines and CSA oscillate in CN.     

Serum interleukin 2 receptor levels in childhood acute lymphoblastic leukemia

The clinical significance of interleukin 2 receptor (IL2R) concentrations in serum was determined for 344 children with newly diagnosed acute lymphoblastic leukemia (ALL). Serum levels of IL2R in patients (267 to 80,000 U/mL, median 2,007 U/mL) were significantly higher than normal control values (170 to 738 U/mL, median 347 U/mL) (P less than .0001). Measurements in cases of T cell ALL were lower than in the non-T, non-B cases (P = .02). Among the 264 patients with non-T, non-B ALL, but not in those with T cell disease, higher serum IL2R levels (greater than 2,000 U/mL) were associated with a poorer treatment outcome (P = .04). In a multivariate analysis, serum IL2R level contributed independent prognostic information beyond that conveyed by leukocyte count, race, and age (P = .04). One explanation for these results is that soluble IL2R competes with normal lymphocyte- integrated IL2R for the ligand and thus could suppress host antitumor immunity.     

The Football Association Medical Research Programme: an audit of injuries in professional football—analysis of preseason injuries

Objectives: To conduct a detailed analysis of preseason football injuries sustained in English professional football over two competitive seasons.     

程序变温法确定药物降解反应级数

通过电子计算机模拟程序升温加速试验,从理论上阐明了常规的程序升温法不能确定药物降解反应级数的原因是因为同一组数据可由不同的反应级数和活化能的组合所拟合;解决这一问题的关键是在一个变温程序中包含升温和降温部分;据此提出了一种新的程序变温方法(程序升降温法)。利用这种方法,可以真正做到只通过一次程序变温加速试验,就获得包括反应级数在内的药物降解的动力学参数,且确定反应级数的能力与恒温法相近似。     

4-芳杂环单/双氨甲基酚衍生物的合成和量化计算

本文在前报的基础上,设计和合成了4-芳杂环取代的氨甲基酚衍生物28个。初步药理试验表明,多数显示不同程度的抗炎活性。用CNDO/2法计算所得数据提示,该类化合物分子中的氨甲基氮和酚羟基氧与受体正电荷中心的结合,可能对抗炎活性起着重要作用。     

Multiplexed cytokine protein expression profiles from spreading depression in hippocampal organotypic cultures.

Cytokines are involved in ischemic tolerance, including that triggered by spreading depression (SD), yet their roles in neuroprotection remain incompletely defined. The latter may stem from the pleiotropic nature of these signaling molecules whose complexities for interaction might be better deciphered through simultaneous measurement of multiple targeted proteins. Accordingly, the authors used microsphere-based flow cytometric immunoassays and hippocampal organotypic cultures (HOTCs) to characterize the magnitude, time course, and diversity of cytokine (interleukin [IL] 1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, granulocyte-macrophage colony-stimulating factor [GM-CSF], interferon-gamma [IFN-gamma], and tumor necrosis factor-alpha [TNF-alpha]) response to SD. GM-CSF was not detected in HOTCs or media. However, SD triggered a significant, generalized increase in seven cytokines evident in HOTCs 6 hours later, with the remaining cytokine, IL-1beta, becoming significantly different at 1 and 3 days. Additionally, these changes extended to include surrounding media for IL-6 and TNF-alpha by 1 and 3 days. This increase was localized to microglia via immunostaining for IL-1alpha, IL-1beta, and interferon-y. IL-10, although significantly more abundant in HOTCs 6 hours after SD, was significantly less abundant in surrounding media at that time and at 1 day. Finally, the generalized early increase in tissue cytokines later settled to a pattern at 3 days of recovery centering on changes in IL-1alpha, IL-1beta, and TNF-alpha, cytokines capable of modulating ischemic injury.     

Metabolism and storage of catecholamines in rats with pheochromocytoma implants

New England Deaconess Hospital rats implanted with a pheochromocytoma P259 became hypertensive and showed high concentrations of plasma dopamine (42.0 +/- 14.6 ng/ml) and norepinephrine (45.7 +/- 8.4 ng/ml). However, the norepinephrine content of several peripheral tissues of these rats did not differ from those of the New England Deaconess Hospital control rats, and their dopamine content, although slightly higher, was much lower than would have been expected from the plasma dopamine levels. Methylation by catechol-O-methyltransferase did not appear to play a major role in the inactivation of tissue catecholamines since there were no noticeable increases of normetanephrine or 3-methoxytyramine in the tissues of the rats with pheochromocytoma. There was also no increase in conjugated dopamine, in either the sulfate or glucuronide form, in the plasma or tissue of the hypertensive rats, although injection of L-dopa induced a large increase in dopamine sulfate in the plasma and urine of these rats. This finding indicated that, although their sulfoconjugation mechanism was intact and not affected by the pheochromocytoma, it did not participate in the metabolism of dopamine released by the tumor into the blood. On the other hand, plasma and urine of tumor-bearing rats exhibited abnormally high concentrations of homovanillic acid, the main metabolite of dopamine resulting from monoamine oxidase action. In contrast to the control rats, intravenous infusion of free dopamine in rats with pheochromocytoma had no effect on plasma free dopamine levels but increased homovanillic acid levels considerably. The present data underline the important role of monoamine oxidase in the removal of excessive quantities of catecholamines released by the tumor in New England Deaconess Hospital rats with the pheochromocytoma implant.     

Mast Cell Interactions and Crosstalk in Regulating Allergic Inflammation

Purpose of Review

This review summarizes recent findings on mast cell biology with a focus on IgE-independent roles of mast cells in regulating allergic responses.

Recent Findings

Recent studies have described novel mast cell-derived molecules, both secreted and membrane-bound, that facilitate cross-talk with a variety of immune effector cells to mediate type 2 inflammatory responses.

Summary

Mast cells are complex and dynamic cells that are persistent in allergy and are capable of providing signals that lead to the initiation and persistence of allergic mechanisms.

     

Use of pulse oximetry for blood pressure measurement after cardiac surgery

Blood pressure measurement using pulse oximeter waveform change was compared with an oscillometric measurement and the gold standard, intra-arterial measurement, in children after cardiac surgery. Forty six patients were enrolled and divided into groups according to weight. Simultaneous blood pressure measurements were obtained from the arterial catheter, the oscillometric device, and the pulse oximeter. Pulse oximeter measurements were obtained with a blood pressure cuff proximal to the oximeter probe. The blood pressure measurements from the pulse oximeter method correlated better with intra-arterial measurements than those from the oscillometric device (0.77-0.96 v 0.42-0.83). The absolute differences between the pulse oximeter and intra-arterial measurements were significantly smaller than between the oscillometric and intra-arterial measurements in children less than 15.0 kg. The pulse oximeter waveform change is an accurate and reliable way to measure blood pressure in children non-invasively, and is superior to the oscillometric method for small patients.