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PubMed2005

[Comparative assessment of the use of skeletonized and un-skeletonized internal thoracic artery for myocardial revascularization].

BACKGROUND: Skeleting of internal thoracic artery widens possibilities of a surgeon during mammary-coronary bypass grafting but this procedure is associated with augmented risk of damage of internal thoracic artery (ITA). MATERIAL AND METHODS: ITA was used for creation of anastomosis with anterior interventricular artery in 151 patients. It was harvested on pedicle in 82 (group 1) and subjected to skeleting in 69 (group 2) patients. All operations were performed with cardiopulmonary bypass. In group 2 ITA conduits were more frequently used for grafting distal anterior interventricular artery. RESULTS: There were 3 and 0 deaths in groups 1 and 2, respectively. Rates of nonfatal postoperative complications were similar in both groups. Spasms of ITA grafts were more frequent in group 1. CONCLUSION: Skeleting of ITA for mammary coronary bypass grafting compared with its harvesting on pedicle was not associated with increased risk of complications or elevated mortality in early postoperative period.

Blood Flow Velocity↗
PubMed1996

Extracellular matrix signaling from the cellular membrane skeleton to the nuclear skeleton: a model of gene regulation.

It is well established that cells must interact with their microenvironment and that such interaction is crucial for coordinated function and homeostasis. However, how cells receive and integrate external signals leading to gene regulation is far from understood. It is now appreciated that two classes of cooperative signals are implicated: a soluble class including hormones and growth factors and a class of insoluble signals emanating from the extracellular matrix (ECM) directly through contact with the cell surface. Using 3-dimensional culture systems and transgenic mice, we have been able to identify some of the elements of this ECM-signaling pathway responsible for gene regulation in rodent mammary gland differentiation and involution. Our major observations are 1) the requirement for a laminin-rich basement membrane; 2) the existence of a cooperative signaling pathway between basement membrane and the lactogenic hormone prolactin (PRL);3) the importance of beta 1-integrins and bHLH transcription factor(s) and the presence of DNA response elements (exemplified by BCE-1, located on a milk protein gene, beta-casein); and 4) the induction of mammary epithelial cell programmed cell death following degradation of basement membrane. We hypothesize that this cooperative signaling between ECM and PRL may be achieved through integrin- and laminin-directed restructuring of the cytoskeleton leading to profound changes in nuclear architecture and transcription factor localization. We postulate that the latter changes allow the prolactin signal to activate transcription of the beta-casein gene. To further understand the molecular mechanisms underlying ECM and hormonal cooperative signaling, we are currently investigating ECM regulation of a "solid-state" signaling pathway including ECM fiber proteins, plasma membrane receptors, cytoskeleton, nuclear matrix and chromatin. We further postulate that disruption of such a pathway may be implicated in cell disorders including transformation and carcinogenesis.

Animals↗
PubMed2005

Skeletonization of internal thoracic artery affects its innervation and reactivity.

OBJECTIVE: The studies showing the superior characteristics of ITA graft and its impact on the clinical results of coronary artery surgery were performed with ITA harvested almost exclusively as a pedicle. This study assesses the impact of ITA skeletonization on its innervation and reactivity. METHODS: Segments of skeletonized and non-skeletonized ITA were stained with antibodies against protein S-100 to look for the presence of sympathetic nerve fibers. The functional studies were performed on segments of discarded human pedicled ITA that were divided into two 3mm rings, one skeletonized and another non-skeletonized. We compared concentration-effect relationships for the contraction to norepinephrine and endothelium-dependent relaxation to acetylcholine and bradykinin, as well as endothelium-independent relaxation to sodium nitroprusside in skeletonized and non-skeletonized segments of the same ITA. RESULTS: Skeletonized ITA was devoid of protein S-100 positive nerve fibers. It contracted stronger (maximal response 37.0+/-2.04 vs. 25.4+/-1.83mN (P<0.001)) and was twice as sensitive to norepinephrine: pD(2) 6.03+/-0.10 vs. 5.70+/-0.12 (P=0.035). The endothelium-dependent relaxation responses did not differ between skeletonized and non-skeletonized ITA rings. The skeletonized ITA rings appeared over 10 times more sensitive to sodium nitroprusside: pD(2) 6.66+/-0.20 vs. 5.59+/-0.37 (P=0.012)-potency ratio 11.61. The maximal responses did not differ significantly: 112.0+/-6.71 vs. 129.4+/-16.4% (P=0.33). CONCLUSIONS: Skeletonization results in sympathectomy of ITA. It has no effect on endothelium-dependent relaxation but increases reactivity of ITA to norepinephrine. This augmented response to alpha-agonist is small, in comparison with over a ten-fold increase in sensitivity to sodium nitroprusside. Pedicled and skeletonized ITA are functionally significantly different vessels when studied in vitro.

Acetylcholine↗
PubMed1995

Depletion of membrane skeleton in red blood cell vesicles.

A possible physical interpretation of the partial detachment of the membrane skeleton in the budding region of the cell membrane and consequent depletion of the membrane skeleton in red blood cell vesicles is given. The red blood cell membrane is considered to consist of the bilayer part and the membrane skeleton. The skeleton is, under normal conditions, bound to the bilayer over its whole area. It is shown that, when in such conditions it is in the expanded state, some cell shape changes can induce its partial detachment. The partial detachment of the skeleton from the bilayer is energetically favorable if the consequent decrease of the skeleton expansion energy is larger than the corresponding increase of the bilayer-skeleton binding energy. The effect of shape on the skeleton detachment is analyzed theoretically for a series of the pear class shapes, having decreasing neck diameter and ending with a parent-daughter pair of spheres. The partial detachment of the skeleton is promoted by narrowing of the cell neck, by increasing the lateral tension in the skeleton and its area expansivity modulus, and by diminishing the attraction forces between the skeleton and the bilayer. If the radius of the daughter vesicle is sufficiently small relative to the radius of the parent cell, the daughter vesicle can exist either completely underlaid with the skeleton or completely depleted of the skeleton.

Erythrocyte Membrane↗
PubMed2025

Leprosy in skeletons from archaeological sites: A systematic review.

BACKGROUND: Leprosy (Hansen's disease) is an ancient stigmatising infectious disease that remains endemic in many countries. Leprosy-related bone changes that cause disabilities in affected persons are evident in skeletons from archaeological sites. The aim of our synthesis of paleopathological data was to gain insights into the disease's historical distribution and presentation. METHODOLOGY: Systematic review of paleopathological studies describing human remains with signs of leprosy published up to December 2023. Extracted data on bone features from skulls and limbs, including rhinomaxillary syndrome (RMS) in cranial bones and post-cranial bone changes (PCBC) in hands and feet, were summarised, together with genomic data from studies of Mycobacterium leprae ancient DNA. FINDINGS: The 297 skeletons described in 67 studies comprised 264 skeletons from sites in modern-day Europe (117 from England, 68 from Denmark); 23 skeletons from Asia (10 from India), 5 from The Americas, and 4 from the African continent (all from Egypt); 174 (58.6%) were from leprosaria, 255 (85.9%) were adults, 28 (9.4%) adolescent, 14 (4.7%) of indeterminate age. Skeletons dated from 3715 BCE to 1839 CE, peaking around the 15th Century. Probable and possible RMS were identified in 85 (30.5%) and 153 (54.8%) of 279 skeletons with cranial data, respectively. Lower limb pathological PCBC were most prevalent in tarsals (76.6%), metatarsals (81.5%), and feet phalanges (85.6%). In upper limbs, 75.8% of humeri, 65.8% of radii, 61.0% of ulnae and 75.8% of hand phalanges exhibited pathological alterations. From 73 skeletons from 19 genomic studies, M. leprae single nucleotide polymorphism (SNP) type 3 was identified in 59 skeletons (80.8%), SNP type 2 in 11 (15.1%), type 4 in two, and type 1 in one. CONCLUSIONS: Four out of five archaeological skeletons with leprosy exhibited some degree of RMS, which is pathognomonic of the most severe form of the disease, irrespective of whether the skeleton was excavated from a leprosarium (leprosy hospital) or from a public cemetery or other burial site. The relatively small numbers of remains excavated over a wide geographical area and a long time period, and the focus of archaeological studies on skeletons already identified as having leprosy, mean that it is difficult to prove or disprove theories that aim to explain the decline and eventual disappearance of leprosy as a disease in Europe.

Humans↗
PubMed1999

Intraoperative and laboratory evaluation of skeletonized versus pedicled internal thoracic artery.

BACKGROUND: The skeletonization of internal thoracic artery is postulated to improve graft length, early blood flow, sternal blood supply, and postoperative respiratory function. Concern exists that skeletonization may injure internal thoracic artery, precluding good results of surgery. Reports on endothelial function of skeletonized internal thoracic artery are lacking. METHODS: A prospective assessment of early clinical outcomes of 357 consecutive patients undergoing coronary artery bypass grafting was performed: 287 patients with nonskeletonized and 70 with skeletonized left internal thoracic artery (LITA). The lengths of LITA and of its discarded distal segment, as well as free LITA blood flow, were measured. The dose-effect relationship for relaxation to acetylcholine was studied in the organ bath. RESULTS: Apart from a higher incidence of breaching the pleura with nonskeletonized LITA the clinical outcomes were comparable. The length of skeletonized LITA was 17.8+/-1.14 cm versus 20.3+/-0.52 cm skeletonized (p = 0.11). The length of discarded LITA was shorter in nonskeletonized artery (0.8+/-0.28 cm versus 2.6+/-0.49 cm; p = 0.022). The free LITA blood flow was 66.3+/-7.42 mL/min in nonskeletonized vessel versus 100.3+/-14.84 mL/min in skeletonized (p = 0.048). The acetylcholine-induced relaxation was similar in both groups (maximal relaxation, 80.7%+/-5.95% in nonskeletonized versus 72.9%+/-9.11% in skeletonized; not significant; negative logarithm of half-maximal effect, 7.43+/-0.18 versus 7.1+/-0.10, respectively; p = 0.063). CONCLUSIONS: Skeletonization does not damage the endothelial function of the LITA. Higher free blood flow and available LITA length should encourage the use of skeletonized LITA in clinical practice.

Acetylcholine↗
PubMed2006

Skeletonized internal thoracic artery harvest reduces pain and dysesthesia and improves sternal perfusion after coronary artery bypass surgery: a randomized, double-blind, within-patient comparison.

BACKGROUND: Observational studies suggest that skeletonization of the internal thoracic artery (ITA) can improve conduit flow and length and reduce deep sternal infections and postoperative pain. We performed a randomized, double-blind, within-patient comparison of skeletonized and nonskeletonized ITAs in patients undergoing coronary surgery. METHODS AND RESULTS: Patients (n = 48) undergoing bilateral ITA harvest were randomized to receive 1 skeletonized and 1 nonskeletonized ITA. Intraoperatively, ITA flow was assessed directly and with a Doppler flow probe before and after topical application of papaverine. ITA harvest time and conduit length were recorded. A blinded assessment of pain (visual analog scale) and dysesthesia (physical examination) was performed at discharge, at 2 weeks, and at a 3-month follow-up. Sternal perfusion was assessed with nuclear imaging (n = 7). Skeletonization required longer ITA harvest times (27 +/- 1 versus 24 +/- 1 minutes; P = 0.04). There was a trend toward increased ITA length in the skeletonized group (18.2 +/- 0.3 versus 17.7 +/- 0.3 cm; P = 0.09). In situ ITA flow was lower in skeletonized arteries (7.4 +/- 0.9 versus 10.1 +/- 1.0 mL/min; P = 0.01) and increased significantly after ITA division and papaverine application. Postanastomotic flows were similar between groups. Skeletonization was associated with decreased pain at the 3-month follow-up and a reduction in major sensory deficits at the 4-week and 3-month (17% versus 50%; P = 0.002) follow-ups. Baseline adjusted sternal perfusion was significantly greater by 17 +/- 6% (P = 0.03) on the skeletonized side. CONCLUSIONS: Skeletonization results in reduced postoperative pain and dysesthesia and increased sternal perfusion at follow-up but does not produce increased conduit flow. ITA skeletonization may be a strategy for reducing morbidity after CABG.

Coronary Artery Bypass↗
PubMed1986

Protective effect of the membrane skeleton on the immunologic reactivity of the human red cell Rho(D) antigen.

It has recently been shown that the 30,000 m.w. Rho(D) protein is associated with the membrane skeleton of the human red cell. We have studied the effects of the membrane skeleton on the immunoreactivity of the Rho(D) antigen present in Rho(D)+ membranes. Solubilization of the membranes with the Triton X-100 detergent and centrifugation of the extracts showed that more than 90% of the immunoreactive Rho(D) antigen sedimented with the membrane skeleton structures. The skeleton-bound Rho(D) antigen could be solubilized by disruption of the skeleton in low ionic strength medium. The removal of the membrane skeleton structure before the solubilization of the membranes with detergent resulted in the inactivation of the majority of the Rho(D) antigen. The effect of the membrane skeleton on the stability of the Rho(D) antigen was additionally studied in detergent extracts prepared from native and skeleton-free membranes. The assay of the Rho(D) antigen activity in the extracts showed that the Rho(D) antigen was 100 times more sensitive to the detergent inactivation in skeleton-free membranes than in native membranes. These results indicate that the membrane skeleton is important for stabilizing the immunoreactive form of the Rho(D) protein on the red cell membrane.

Antigen-Antibody Reactions↗
PubMed2006

[Okuda wooden human skeleton made in Edo era, Japan].

Probably in 1820 (late Edo era), a human skeleton for medical education was carved from cypress wood, based on a criminal's skeleton under the supervision of a medical doctor, Banri Okuda in Osaka City. The skeleton is called "Okuda wooden skeleton" and is now housed in the National Science Museum, Tokyo. The bones can be assembled into a skeleton by metal pivots or bamboo sticks. The thorax and pelvis were made of several pieces of wood and combined together, respectively. By and large, the wooden skeleton shows morphological characteristics usually seen in early middle-aged females of the Edo era. But the claviculae, distal ends of the femora, and the patellae are exceptionally larger than those of a female, implying that these bones of the original skeleton had already been lost or were deformed before the wooden skeleton was made. Actually the wooden skeleton might not have been used for medical education but rather for the promotion of European medicine, which was gradually developing in the Edo era.

Anatomy↗