Editorial

Aim: Wall stress‐independent signalling pathways were studied for endothelin‐1 (ET‐1)‐induced c‐fos expression in rat intact mesenteric small arteries. Methods: Arteries were kept unmounted in Krebs buffer, equilibrated for 1 h and stimulated with vasoactive substances for 15–60 min. The c‐fos mRNA expression was determined by real‐time polymerase chain reaction. Results: Stimulation with fetal bovine serum (FBS), phorbol 12‐myristate 13‐acetate (PMA) and ET‐1 caused about a doubling of c‐fos mRNA. The ET‐1‐induced c‐fos expression was steady (15–60 min) and was inhibited by the inhibitor of the ET_A receptor, BQ‐123. Platelet‐derived growth factor‐B, angiotensin II and U46619 did not cause increased c‐fos mRNA levels. The broad specificity inhibitor staurosporine inhibited the response to ET‐1, but inhibitors of Rho‐A kinase and phosphatidylinositol 3‐kinase had no effect. However, inhibitors to tyrosine kinases, the MAP kinases [extracellular signal‐regulated kinase 1/2 (ERK1/2), c‐Jun amino‐terminal kinase, p38], and to conventional protein kinase C showed no inhibition. Consistent with these findings, ET‐1 did not cause activation of ERK1/2, a finding also seen in vessels held under pressure. In contrast, ET‐1‐induced c‐fos expression was inhibited by the calcium chelator BAPTA, suggesting a role for intracellular calcium. This possibility was supported by the finding that raising the extracellular K⁺ concentration caused increased expression of c‐fos in a concentration‐dependent manner. Conclusion: The results suggest that in the absence of wall stress, ET‐1 is able to induce increased expression of c‐fos independent of traditional growth pathways, such as MAP kinase. The mechanism appears to be calcium‐dependent.     

前锯肌下部肌皮瓣移植的应用解剖

目的：为前锯肌下部肌皮瓣移植提供解剖学基础。方法：在２５具（５０侧）成人尸体标本上，对前锯肌下部的形态、血供和神经支配进行了应用解剖学观测。结果：前锯肌下部的血供主要来自胸背动脉的前锯肌支，外径１．３±０．２ｍｍ，伴行静脉外径１．５±０．２ｍｍ，长４．９±１．１ｃｍ；由胸长神经支配，其横径为１．７±０．４ｍｍ，神经干长７．７±１．４ｃｍ。结论：以胸背血管及前锯肌支为血管蒂和胸长神经为蒂可切取前锯肌下部１２．０ｃｍ×９．０ｃｍ的肌皮瓣，修复较大创面或重建肌动力     

Interactions between membrane IgM and the cytoskeleton involve the cytoplasmic domain of the immunoglobulin receptor

Cross-linking induced interactions between the membrane form of immunoglobulin (mIg) and the cytoskeletal matrix have been described by several groups. To date, the function of mIgM association with the cytoskeleton is not yet understood. Delineation of the molecular basis of these interactions will be instrumental in elucidating their function. We have previously shown that the Igα/β heterodimer is not required for ligand-induced mIgM binding to the cytoskeleton. In this study, we have investigated the role of other B cell-specific proteins in mediating these interactions. For this, we expressed mIgM in the non-hematopoietic human cervical carcinoma cell line HeLa S3 and verified the capacity of the surface-expressed IgM to interact with the cytoskeletal matrix upon cross-linking with anti-μ chain antibodies. We show here that only the mIgM molecule itself and no other B cell-specific protein(s) is required in mediating mIgM interactions with actin filaments. In an attempt to determine the cytoskeleton-binding site of mIgM we investigated the role of the cytoplasmic tail of mIgM (KVK) in binding the receptor to actin-based microfilaments. Using mutated forms of mIgM expressed in J558L cells, we show here that KVK plays a role in mediating these interactions. The absence of KVK did not, however, completely abrogate mIgM-cytoskeletal interactions, suggesting that there are additional molecular requirements for the ligand-induced mIgM binding to the cytoskeletal matrix.     

Depriving neonatal rats of milk from early lactation has long-term consequences on mammotrope development

The sudden appearance of prolactin-releasing cells during the early postnatal period of the rat is initiated by a small milk-borne peptide. Depriving newborn rats of this early milk factor severely retards mammotrope differentiation during the neonatal period. In the present work, we extend our study of early milk deprivation to the adult. To this end, newborn litters were crossfostered onto mothers that had given birth the same day or one week earlier in order to deprive pups in the latter group of early milk. At 5, 15, and 30 d of age, rats deprived of such milk had decreased percentages of mammotropes (as measured by reverse hemolytic plaque assay, RHPA) when compared to nondeprived animals (P<0.05). By 45 d, the percentage of mammotropes was similar for the two crossfostered groups (P>0.1) and this persisted through d 60. Subsequently, we assessed the secretory capacity of mammotropes from 60-d old rats to secretagogues and found that early milk deprivation had no effect on basal prolactin release (P>0.1), but that it augmented hormone secretion evoked by thyrotropin-releasing hormone (TRH, 100 nM; P<0.01). The inhibitory response to dopamine (DA; 1 μM) and the stimulatory response to angiotensin II (AGII; 100 nM) were not altered by early milk deprivation (P>0.1). Taken together, these results demonstrate that factors in milk from early lactation are required for normal mammotrope differentiation, and that the delay induced by early milk deprivation leads to altered secretory function of mammotropes in adult animals.     

Transesophageal Echocardiographic Analysis of the Systolic Pattern of the Anterior Mitral Leaflet in Patients with Flat Chest

Transesophageal echocardiography was conducted to determine the systolic pattern of the anterior mitral leaflet in patients with flat chest, and to differentiate it from that associated with mitral valve prolapse. The fronto-sagittal index (an index of chest flattening) was determined in 50 subjects using chest radiographs, and was used to classify them into a flat chest group (index < 0.38, n = 28) and a normal chest group (index ≥ 0.38, n = 22). We then used transesophageal echocardiography to examine the anterior leaflet in these subjects. A significant positive correlation was observed between the fronto-sagittal index and the short-to long-axis diameter ratio of the left ventricle in all patients. These parameters, and the left atrial dimension were lower in the flat than the normal chest group. The clear zone area of the anterior leaflet during mid-to late-systole was significantly larger in the flat chest group. However, no intergroup differences existed in the rough zone area of the anterior leaflet or in the middle scallop area of the posterior leaflet. Mitral regurgitation was observed in 20 and 12 subjects in the flat and normal chest groups, respectively. The maximum mitral regurgitant area did not differ between the two groups. The clear zone area of the anterior leaflet increased significantly following inhalation of amyl nitrite in 22 subjects of both groups, but the other areas did not increase. The mitral regurgitant area decreased or disappeared after amyl nitrite at a similar rate in each group. Thus, the decrease in the antero-posterior dimension of the thorax in subjects with flat chest affects the systolic pattern of the clear zone of the anterior leaflet more than that of the rough zone of the anterior leaflet or the posterior leaflet. This systolic pattern in such patients differs from that associated with mitral valve prolapse.     

经导管动脉内溶栓治疗急性动脉血栓栓塞

5例急性动脉血栓栓塞患者行经导管动脉内溶栓治疗 ,其中 4例一次溶栓成功 ,1例经两次溶栓成功 ,无一例出现并发症。对于急性动脉血栓形成的治疗过去常用静脉滴注溶栓剂的方法 ,小剂量效果不明显 ,加大剂量又易发生出血并发症。而采用经动脉插管至局部血栓部位灌注溶栓药物 ,并发症少 ,效果明确     

Does a tensioning device pinned to the tibia improve knee anterior–posterior load‐displacement compared to manual tensioning of the graft following anterior cruciate ligament reconstruction? A cadaveric study of two tibial fixation devices

Devices that are pinned to the tibia to tension an anterior cruciate ligament (ACL) graft produce joint reaction loads that in turn can affect the maintenance of graft initial tension after tibial fixation and hence knee anterior-posterior (AP) load-displacement. However, the effect of these devices on AP load-displacement is unknown. Our objectives were to determine whether tensioning by device versus tensioning by hand causes differences in AP load-displacement and intraarticular graft tension for two commonly used tibial fixation devices: a bioresorbable interference screw and a WasherLoc. AP load-displacement and intraarticular graft tension were measured in 20 cadaveric knees using a custom arthrometer. An initial tension of 110 N was applied to a double-looped tendon graft with the knee at extension using a tensioning device pinned to the tibia and a simulated method of tensioning by hand. After inserting the tibial fixation device, the 134 N anterior limit (i.e., anterior position of the tibia with respect to the femur with a 134 N anterior force applied to the tibia) and 0 N posterior limit (i.e., AP position of the tibia relative to the femur with a 0 N force applied to the tibia) were measured with the knee in 25 degrees flexion. Intraarticular graft tension was measured at extension. These limits and intraarticular graft tension were also measured after cyclically loading the knee 300 times. Compared to a simulated method of tensioning by hand, tensioning with a device pinned to the tibia did not decrease the 134 N anterior limit and did not cause posterior tibial translation. However, intraarticular graft tension was maintained better with a tensioning device pinned to the tibia for the Washerloc, but not the interference screw. For two commonly used tibial fixation devices, a tensioning device pinned to the tibia does not improve AP load-displacement at 25 degrees flexion over tensioning by hand when the graft is tensioned at full extension, but does improve the maintenance of intraarticular graft tension for the Washerloc.     

The organization of trigeminotectal and trigeminothalamic neurons in rodents: a double-labeling study with fluorescent dyes

Retrogradely transported fluorescent dyes (fast blue and diamidino-dihydrochloride yellow) were used to compare the distributions of trigeminofugal neurons that project to the superior colliculus and/or the thalamus in three rodent species. The objective was to determine what the projection and collateralization patterns of these trigeminofugal pathways are and whether they are similar among different species. In each anesthetized animal, one dye was injected into the superior colliculus and the other into the topographically congruent area of the thalamus. Counts of the numbers of yellow, blue, and double-labeled neurons were made throughout the trigeminal complex: principalis, pars oralis, pars interpolaris, and pars caudalis. Trigeminothalamic projections were similar in each of the rodent species studied. The densest concentration of retrogradely labeled neurons was in principalis, with substantially fewer neurons in pars interpolaris, and fewer still in pars oralis and pars caudalis. These neurons were generally small and tended to have round or fusiform somata. A common pattern was also noted among the three species for trigeminotectal neurons. Most trigeminotectal projections originated from neurons in pars interpolaris, somewhat fewer from pars oralis, and the fewest from principalis and pars caudalis. These neurons tended to be the largest in each subdivision and were often multipolar. Following paired injections of the tracers, double-labeled neurons were scattered throughout the sensory trigeminal complex and had morphologies characteristic of single-labeled trigeminotectal neurons. Although comparatively few double-labeled neurons were observed in any species, most of those seen were restricted to the ventrolateral portion of pars interpolaris, a position that corresponds to the representation of the vibrissae. These data indicate that, regardless of the rodent species, the vast majority of labeled trigeminal neurons project either to the superior colliculus or the thalamus, but not to both targets. This might be expected on the basis of the very different behavioral roles these structures play. On the other hand, a subpopulation of trigeminal neurons exists (mainly in pars interpolaris) that does project to both the superior colliculus and the thalamus, perhaps because both structures require some of the same somatosensory information to perform their behavioral functions.     

Influence of melatonin on bovine pulmonary vascular and bronchial airway smooth muscle tone

The influence of melatonin on tension of isolated bovine pulmonary vascular and bronchial smooth muscle rings were examined in these experiments. Melatonin caused a dose-dependent relaxation of precontracted (30 mM KCl) pulmonary artery and vein, although the effect is greater in arterial smooth muscle. This relaxant response was blocked by preincubating vessels with antagonists of vasoactive intestinal peptide or Substance P. In bronchial smooth muscle, melatonin caused a small contractile response. These experiments demonstrate that in response to melatonin the pulmonary vasculature relaxes, while in airway smooth muscle the reverse, constriction, occurs. It is hypothesized that nocturnal exaggeration of asthma may, in part, be due to changes in circulating levels of melatonin.     

Altered neuropeptide Y Y1 responses in mesenteric arteries in rats with congestive heart failure

The aim of the present study was to elucidate if the potentiating effect of neuropeptide Y on various vasoactive agents in vitro is (1) altered in mesenteric arteries from rats with congestive heart failure and (2) mediated by the neuropeptide Y Y₁ receptor. The direct vascular effects of neuropeptide Y and its modulating effects on the contractions induced by endothelin-1-, noradrenaline-, 5-hydroxytryptamine (5-HT)-, U46619-(9, 11-dideoxy-11, 9-epoxymethano-prostaglandin F₂) and ATP, and acetylcholine-induced dilatations were studied in the presence and absence of the neuropeptide Y Y₁ antagonist, BIBP3226 (BIBP3226{(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]- -arginine-amide}). Neuropeptide Y, per se, had no vasoactive effect in the arteries. The potency of endothelin-1 was significantly decreased in congestive heart failure rats. Neuropeptide Y and neuropeptide Y-(13–36) potentiated the endothelin-1-induced contraction in congestive heart failure mesenteric arteries. In 20% of the congestive heart failure rats, sarafotoxin 6c induced a contraction of 31±4%. Neuropeptide Y also potentiated U46619- and noradrenaline-induced contractions but not 5-HT-induced contractions in congestive heart failure arteries. In sham-operated animals neuropeptide Y potentiated noradrenaline- and 5-HT-induced contractions. These potentiations were inhibited by BIBP3226. Acetylcholine induced an equipotent relaxation in both groups which was unaffected by neuropeptide Y. In conclusion, neuropeptide Y responses are altered in congestive heart failure rats. The potentiating effect differs between vasoactive substances. Neuropeptide Y Y₁ and non-neuropeptide Y₁ receptors are involved.