Postmitotic marrow neutrophils and neutrophil mobilization in man: role of the spleen

The relationship between postmitotic marrow neutrophils (PMMN) and neutrophil increment in blood after an intravenous dose of 3 mg hydrocortisone/kg was studied in patients with normal-sized spleens and compared with splenectomized and splenomegalic patients. PMMN were quantified from the ferrokinetic measurement of the normoblast number and the PMMN/normoblast ratio in bone marrow biopsy sections. In 12 control patients with normal PMMN the increment was 3.50 +/- 1.13 X 10(9) neutrophils/liter. An excellent correlation was found between the number of PMMN and the maximal neutrophil increment (y = 826x - 1021, r = 0.93, p less than 0.001) among 24 patients with normal spleen size and a wide range of marrow cellularity. Significantly higher responses were observed in 10 splenectomized patients (y = 872x + 1429, r = 0.92, p less than 0.001). The two regression lines were shown to be parallel, indicating a diminution of the response by 2.5 X 10(9) neutrophils/liter in the presence of a normal spleen. In 11 hypersplenic patients the responses were further reduced and more variable. Peak neutrophilia occurred after median values of 2, 3, and 4 hr in the hypersplenic, the control, and the splenectomized group, respectively. These studies indicate that allowing for the different response curves neutrophil increments may be used as an index of PMMN in patients with normal spleen size and in splenectomized patients. They further suggest sequestration of the prematurely released cells by the spleen.     

Responses of lipolysis and salivary cortisol to food intake and physical activity in lean and obese children

This investigation was conducted to determine whether there were differences in lipolytic responses to feeding and physical activity between lean (LN) and obese (OB) children, and if these responses were related to cortisol. Fourteen LN and 11 OB children participated in this study of abdominal lipolysis and salivary cortisol response to breakfast and lunch with an intervening exercise session. Calculated fasting glycerol release was lower in OB than LN (0.645 +/- 0.06 vs. 0.942 +/- 0.11 micromol/ml; P < 0.05). Fasting adipose tissue nutritive flow was lower in OB than in LN subjects, but responses to feeding and exercise were not different. Breakfast elicited a decrease in interstitial glycerol concentration in LN (-33%; P < 0.05), but not in OB (-5%), children, although decreases in glycerol concentration in response to lunch were similar (LN, -41%; OB, -36%). An interaction was evident in the salivary cortisol response to breakfast (LN, no change; OB, increase) and exercise (LN, no change; OB, decrease), but there were no group differences in response to lunch. Alterations in salivary cortisol and lipolysis were not related. These data suggest that salivary cortisol and lipolytic responses are not necessarily linked, but are altered in obesity. Furthermore, prior exercise may improve the antilipolytic response to a meal in OB children.     

模拟后路椎间盘镜下腰椎间盘摘除术与传统术式治疗腰椎间盘突出症对腰椎生物力学稳定性的影响

目的探讨后路椎间盘镜下腰椎间盘摘除术(MED)及传统开放腰椎间盘摘除术对腰椎生物力学稳定性的影响。方法选用6具新鲜尸体脊柱标本,模拟后路腰椎间盘摘除的不同术式,依次对标本腰3～4间隙进行处理,共设计5种减压情况:MED、半椎板切除、半椎板切除并下关节突1/2切除、半椎板切除并下关节突全部切除和全椎板切除髓核摘除术。在力学实验机上分别对实验标本进行前屈/后伸、左/右侧屈及左/右轴向旋转运动,测量不同运动的最大范围。结果模拟MED手术脊柱标本向各个方向的运动与正常对照组比较差异无统计学意义(P>0.05);半椎板切除术、半椎板切除并下关节突1/2切除后,标本向各个方向的运动除半椎板切除并下关节突1/2切除后右侧旋转外与正常对照组差异无统计学意义(P>0.05),半椎板切除并下关节突全部切除后,标本向各个方向运动与正常对照组比较差异均有统计学意义(P<0.05,右侧旋转P<0.01);模拟全椎板切除标本向各个方向的运动与正常对照组比较差异均有统计学意义(P<0.01)。结论MED手术对脊柱破坏性较小,对稳定性无影响,而半椎板并小关节切除则破坏了稳定性。     

Computer-aided drug-discovery techniques that account for receptor flexibility

Protein flexibility plays a critical role in ligand binding to both orthosteric and allosteric sites. We here review some of the computer-aided drug-design techniques currently used to account for protein flexibility, ranging from methods that probe local receptor flexibility in the region of the protein immediately adjacent to the binding site, to those that account for general flexibility in all protein regions.