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Circadian rhythms in the rat: constant darkness, entrainment to T cycles and to skeleton photoperiods.

Free running activity and drinking rhythms of male Sprague-Dawley rats were observed in constant darkness (DD) for up to 44 days. The average period of the rhythms (tau DD) was 24.2 hr (+/- 0.12 hr) and the activity time was near one half of the circadian cycle. In the second experiment, rats were entrained to T cycles (T = period) with 2 hr of light per cycle. At T = 23 and T = 26 about one half of the rats entrained indicating that these periods are near the limits of entrainment. T = 23 induced a lasting aftereffect on tau DD while T = 26 affected tau DD only briefly. In contrast to some other nocturnal rodents, activity time was not compressed as T neared the limits of entrainment. In the third experiment, rats and hamsters were entrained to 24 hr skeleton photoperiods (two 1 hr light pulses/cycle). Rats phase jumped to the longer subjective night when the interval between the light pulses was reduced to 6 or 5 hr, while most hamsters phase jumped at 3.5 hr. Furthermore, all rats phase jumped by means of delaying transients while most hamsters showed advancing transients. Finally, while skeleton photoperiods compressed activity time in hamsters to 6 hr or less, activity time remained fairly constant in rats. These results demonstrate considerable differences in the organization of the circadian system among commonly studied nocturnal rodents.

Animals↗

Effects of melatonin in blocking the response to a skeleton photoperiod in the blackheaded bunting.

This investigation examined whether a long-day photoperiodic response induced in an interrupted-night (skeleton) photoschedule could not be induced if a short-day melatonin signal was maintained by exogenous melatonin. Three experiments, lasting for 30 days, were performed using photosensitive adult male birds. In Experiment 1, two groups (n = 12 each) were exposed to a skeleton photoperiod (6L:6D:1.5L:10.5D) and received daily either melatonin (10 micrograms bird-1 day-1) or saline (controls) in between 0.5 and 0.25 h prior to the onset of 1.5 h light pulse. Experiments 2 and 3 were similar to the Experiment 1, except in that the duration of the light break was reduced to 1 h (i.e., 6L:6D:1L:11D) and the dose of melatonin was increased to 25 micrograms bird-1 day-1 (Exp. 2) or 100 micrograms bird-1 day-1 (Exp. 3). In addition, one group of 12 birds was maintained on 6L:18D and served as noninjected controls. Although all melatonin treatments reduced fattening and weight gain (p < 0.05, compared to vehicle-treated controls), and the suppressive effects progressively increased with increasing dose of melatonin, in none of the groups were these reduced to the values found in short-day controls. Gonadal growth occurred in all groups but in birds that received 100 micrograms of melatonin photostimulated testes were significantly smaller than the vehicle-treated controls. In buntings exogenous melatonin, which encounters the suppressive effects of mid-night light pulse on melatonin peak (elevated nocturnal melatonin levels), seems not to completely block the inductive effects of light pulse. It is suggested that melatonin may not be involved in the circadian system regulating photoperiodic responses in birds, but may have peripheral effects on the neuroendocrine circuitry.

Animals↗

Hemolytic anemias due to disorders of red cell membrane skeleton.

During the past 10 years, knowledge of the composition, function and supramolecular assembly of the red cell membrane has been greatly expanded by progress in molecular and cell biology. Detailed information on the organization of membrane cytoskeletal proteins and their molecular characterization has allowed us to correlate a number of protein abnormalities with clinical symptoms that are peculiar to hereditary hemolytic anemias (HHA). In particular, three general principles emerge that can help us to understand the pathogenetic mechanisms of HHA: (a) protein-protein and protein-lipid interactions greatly influence the correct assembly of the membrane skeleton; (b) the red blood cell (RBC) membrane skeleton mostly determines the shape (discocyte), deformability (rheologic properties) and durability (half-life and resistence to shear stress) of the erythrocytes; (c) changes in cytoskeletal composition and/or organization can produce alterations in all of the above properties, and therefore they are responsible for the onset of the hemolytic damage.

Anemia, Hemolytic↗

MESA is a Plasmodium falciparum phosphoprotein associated with the erythrocyte membrane skeleton.

The mature-parasite-infected erythrocyte surface antigen (MESA) of Plasmodium falciparum is an antigenically variable, high molecular weight protein of trophozoites and schizonts that is located at the erythrocyte surface membrane. It is first synthesized at the late ring stage and continues to be synthesized until late schizogony. MESA cannot be detected on the external surface of erythrocytes infected by trophozoites and early schizonts but is located at the internal surface in association with the erythrocyte membrane skeleton. The degree of association with the membrane skeleton varies among parasite lines, being greater in knobby parasite lines. MESA is phosphorylated and is present in a similar location to another phosphoprotein, the ring-infected erythrocyte surface antigen (RESA). However, it differs from RESA in being detected at a later stage of asexual development of the parasite.

Animals↗

Multifocal central giant cell lesions of the maxillofacial skeleton: a case report.

The classification of giant cell lesions of the maxillofacial skeleton is one that remains controversial. Classifying giant cell lesions of the jaw as granulomatous based solely on location seems inappropriate. The categories of benign or malignant are more realistic. Benign lesions may then be subdivided into aggressive and nonaggressive. Multifocal giant cell lesions strongly suggest the brown tumor of hyperparathyroidism. Serum chemistry tests including calcium, phosphorus, ionized calcium, and PTH levels should routinely be obtained when a giant cell lesion is suspected. A case of benign, aggressive, multifocal central giant cell lesions of the maxillofacial skeleton, in the absence of either primary or secondary hyperparathyroidism is presented. Whether this represents metastasis from the initial lesion, metabolic osteoclastic dysfunction, or a new entity, craniofacial giant cell dysplasia, is unknown.

Adult↗

Limited proteolysis of the erythrocyte membrane skeleton by calcium-dependent proteinases.

The action of purified calcium-dependent proteinases on human erythrocyte membrane skeleton proteins has been examined. Preferential cleavage of proteins 4.1 a and b and band 3 and limited cleavage of alpha- and beta-spectrin occur when either calcium-dependent proteinase I or calcium-dependent proteinase II has access to the cytoplasmic side of the ghost membrane skeleton in the presence of calcium. Thus, when these proteinases are incubated with sealed ghosts they do not cleave these proteins. Leupeptin, mersalyl, the specific cellular protein inhibitor of these enzymes, and calcium chelators can inhibit proteolysis of the red cell ghost proteins by Ca2+-dependent proteinases. Each proteinase has also been loaded into erythrocyte ghosts in the absence of calcium at low ionic strength and subsequently trapped inside by resealing the ghosts. The proteinases were activated by incubating these ghosts in the presence of the calcium ionophore A23187 and calcium. Examination of the ghost proteins by electrophoresis demonstrated calcium-dependent proteolysis of Bands 4.1 and 3 and limited cleavage of alpha- and beta-spectrin similar to that observed on proteolysis of the open, leaky ghosts. In the presence of calcium each calcium-dependent proteinase appears to associate with the erythrocyte ghost membrane.

Anion Exchange Protein 1, Erythrocyte↗

Locally challenging osteo- and chondrogenic tumors of the axial skeleton: results of combined proton and photon radiation therapy using three-dimensional treatment planning.

PURPOSE: Tumors of the axial skeleton are at high risk for local failure. Total surgical resection is rarely possible. Critical normal tissues limit the efficacy of conventional photon therapy. This study reviews our experience of using combined high dose proton and photon radiation therapy following three-dimensional (3D) treatment planning. METHODS AND MATERIALS: Between December 1980 and September 1992, 47 patients were treated at the Massachusetts General Hospital and Harvard Cyclotron Laboratory for primary or recurrent chordomas and chondrosarcomas (group 1, 20 patients), osteogenic sarcomas (group 2, 15 patients) and giant cell tumors, osteo-or chondroblastomas (group 3, 12 patients). Radiation treatment was given postoperatively in 23 patients, pre- and postoperatively in 17 patients, and 7 patients received radiation therapy as definitive treatment modality following biopsy only. The proton radiation component was delivered using a 160 MeV proton beam and the photon component using megavoltage photons up to 23 MV energy with 1.8-2.0 Cobalt Gray Equivalent (CGE) per fraction, once a day. Total external beam target dose ranged from 55.3 CGE to 82.0 CGE with mean target doses of 73.9 CGE (group 1), 69.8 CGE (group 2), and 61.8 CGE (group 3). RESULTS: Group 1 (chordoma and chondrosarcoma): Five of 14 patients (36%) with chordoma recurred locally, and 2 out of 5 patients developed distant metastasis, resulting in 1 death from disease. A trend for improved local control was noted for primary vs. recurrent tumors, target doses > 77 CGE and gross total resection. All patients with chondrosarcoma achieved and maintained local control and disease-free status. Five-year actuarial local control and overall survival rates were 53% and 50% for chordomas and 100% and 100% for chondrosarcomas, respectively. Group 2 (osteogenic sarcoma): Three of 15 patients (20%) never achieved local control and died within 6 months of completion of radiation treatment. Only 1 out of 12 patients who were controlled for more than 6 months failed locally, yielding a 5-year local control rate of 59% for 15 patients. Overall, 4 patients (27%) developed distant metastasis (two in patients with uncontrolled primary); 4 patients succumbed to their disease, 3 patients died of intercurrent disease, resulting in overall survival of 44% at 5 years. Group 3 (giant cell tumors, osteo- and chondroblastoma): One of 8 patients with giant cell tumor failed locally, 1 patient distantly, and all patients are alive. Three of 4 patients with osteo- or chondroblastoma are alive and well. One patient suffered local recurrence and died of disease. Local control rate and overall survival for this group of 12 patients was 76% and 87% and local control for patients with giant cell tumors 83% at 5 years. In the majority of cases radiotherapy was well tolerated. However, one patient with a large base of skull tumor developed retinopathy, one patient required enucleation of a previously blind eye, and another patient with sacral tumor developed chronic diarrhea. CONCLUSION: Combined proton and photon radiation therapy optimized by 3D treatment planning, allows the delivery of higher radiation doses to tumors of the axial skeleton, while respecting normal tissue constraints. High radiation doses can result in improved long-term local control.

Adolescent↗

CT studies of tumors of the skull base, facial skeleton and nasopharynx.

Fifty cases of tumors of the base of the skull, facial skeleton and nasopharynx were studied by CT. The tumoral densities were measured and compared to the pterygoid muscle density which was used as reference. Results showed no relationship between tumoral density and histology, and intravenous contrast medium injection was not useful. CT, however, does offer many advantages in the diagnosis of nasopharynx tumors, (5 cases) and in the determination of the extension of facial skeleton tumors.

Humans↗

Relationship between the carbon skeleton length of ketonic solvents and potentiation of chloroform-induced hepatotoxicity in rats.

Previous studies have suggested that ketonic solvents potentiate the hepatotoxic action of CHCl3 in rats. In addition, the relative potentiating capacity of the ketones appeared to be related to the length of their carbon skeleton. To test this hypothesis CHCl3-induced liver injury was evaluated in male Sprague-Dawley rats pretreated (15 mmol/kg, p.o.) with acetone (Ac), 2-butanone (Bu), 2-pentanone (Pn), 2-hexanone (Hx) or 2-heptanone (Hp). After 18 h, a challenging dose of CHCl3, (0.50 or 0.75 ml/kg, i.p.) was given. Liver damage was evaluated 24 h after CHCl3 administration by determining elevations in plasma GPT and OCT activity. Neither Ac, Bu, Pn, Hx, Hp or the CHCl3 challenging dosages produced marked liver injury when given alone. However, each of the ketones potentiated CHCl3-induced liver damage. The severity of the potentiated hepatotoxic response was significantly (positively) correlated with the ketone carbon chain length. These observations suggest that carbon skeleton length may play a role in determining the relative potentiating capacity of ketonic solvents.

Alanine Transaminase↗

Anatomically guided surgery to the AV node. AV nodal skeletonization: experience in 46 patients with AV nodal reentrant tachycardia.

We report our combined experience with operative therapy for atrioventricular nodal tachycardia using an anatomically guided procedure. The operative rationale was to dissect the AV node with the intent of modifying perinodal tissues (skeletonization). The anterior septal and posterior septal regions were initially approached epicardially to facilitate endocardial dissection. Under normothermic cardiopulmonary bypass, the right atrial septum was mobilized and the intermediate AV node was exposed anterior to the tendon of Todaro. Ablation of concomitant accessory pathways was done prior to AV nodal skeletonization. Forty-six patients aged 9-71 years (mean 36) were operated upon. Five patients had accessory pathways in addition to AV nodal reentry. At electro-physiological study prior to discharge, no patient had an AV block although anterograde and retrograde Wenckebach cycle lengths were significantly prolonged. Ten patients had a retrograde AV block. The 46 patients were free of arrhythmia and not taking antiarrhythmic medication after a follow-up of 1-45 months (mean 17). Three patients had a recurrence of the tachycardia 10 days, 2 months and 7 months post-operatively, respectively. All patients had a subsequently successful reoperation.

Adolescent↗

Neural net applied to anthropological material: a methodical study on the human nasal skeleton.

A new information processing method, an artificial neural net, was applied to characterise the variability of anthropological features of the human nasal skeleton. The aim was to find different types of nasal skeletons. A neural net with 15*15 nodes was trained by 17 standard anthropological parameters taken from 184 skulls of the Aachen collection. The trained neural net delivers its classification in a two-dimensional map. Different types of noses were locally separated within the map. Rare and frequent types may be distinguished after one passage of the complete collection through the net. Statistical descriptive analysis, hierarchical cluster analysis, and discriminant analysis were applied to the same data set. These parallel applications allowed comparison of the new approach to the more traditional ones. In general the classification by the neural net is in correspondence with cluster analysis and discriminant analysis. However, it goes beyond these classifications because of the possibility of differentiating the types in multi-dimensional dependencies. Furthermore, places in the map are kept blank for intermediate forms, which may be theoretically expected, but were not included in the training set. In conclusion, the application of a neural network is a suitable method for investigating large collections of biological material. The gained classification may be helpful in anatomy and anthropology as well as in forensic medicine. It may be used to characterise the peculiarity of a whole set as well as to find particular cases within the set.

Adult↗

Incidence of vocal cord dysfunction after fluoroscopically guided steroid injections in the axial skeleton.

OBJECTIVE: To report on the incidence of dysphonia and/or associated throat symptoms after steroid injections in the axial skeleton. DESIGN: A prospective cohort study. SETTING: Academic spine center. PARTICIPANTS: Patients (N = 100) undergoing a diagnostic injection followed by a therapeutic injection in the axial skeleton. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Presence or absence of dysphonia and/or associated throat symptoms, as determined by completion of a predetermined 10-item questionnaire. This questionnaire was administered before participation in the study and at specific intervals after a diagnostic injection and, again, after a therapeutic spinal injection. RESULTS: There was a 12% incidence of transient dysphonia and/or associated throat symptoms in this study population after a therapeutic injection. CONCLUSIONS: Throat symptoms are a potential, albeit transient side effect, after an epidural space corticosteroid injection. The mechanism through which dysphonia or other throat symptoms develop is unknown but appears to be mediated by a systemic steroid effect.

Adult↗

Multivessel, all-arterial, off-pump surgical revascularization without disruption of the thoracic skeleton.

PURPOSE: To evaluate the feasibility of performing multivessel off-pump surgical revascularization without manipulation of the thoracic cage. DESCRIPTION: The technique consists of bilateral thoracoscopic internal mammary artery harvesting followed by a nonrib-spreading, muscle-sparing opening in the soft tissue of the thorax. An endoscopic cardiac positioner and stabilizers exposes and steadies the target arteries beneath a small opening. Anastomoses are constructed off-pump through the natural width of the intercostal space without the need for rib spreading. EVALUATION: Fifty-two patients underwent all-arterial, off-pump revascularization through incisions avoiding manipulation of the thoracic skeleton. The mean number of grafts per patient was 2.2 +/- 0.4. Transit time flow measurements verified graft patency before closure in all cases. The mean operating time was 4.4 hours (range, 3.4 to 5.6). Hospital length of stay was 2.6 +/- 1.9 days. There was no early or late mortality. Postoperative angiography performed in 63.8% of the grafts (74 of 116) revealed an overall patency rate of 98.6%. CONCLUSIONS: A grafting approach that avoids any manipulation of the thoracic skeleton offers significant patient value and may not be limited to single-graft cases.

Aged↗

Routine use of bilateral skeletonized internal thoracic artery grafts in middle-aged diabetic patients.

BACKGROUND: The purpose of this study was to determine whether middle-aged diabetic patients aged less than 70 years could have routine use of bilateral skeletonized internal thoracic artery grafting without an increased surgical risk. METHODS: Between January 1997 and December 2003, 712 consecutive patients aged less than 70 years underwent bilateral internal thoracic artery grafting. Among these, 164 were diabetic and underwent bilateral internal thoracic artery grafting without other preoperative selection than age. The postoperative results of these 164 nonselected consecutive diabetic patients were compared to these of the 548 nondiabetic patients. RESULTS: The operative mortality rate was 4.3% (7 patients) in the diabetic group and 2.4% (13 patients) in the nondiabetic group (p = not significant [NS]). Deep sternal wound infection was observed in 2 patients (1.1%) in the diabetic group and in 6 patients (1.2%) in the nondiabetic group (p = NS). There were no significant difference in the morbidity rate between the two groups except for renal failure without dialysis (6.7% in the diabetic group vs 2.0% in the nondiabetic group, p < 0.01). CONCLUSIONS: Routine use of bilateral internal thoracic artery grafting was performed in nonselected middle-aged diabetic patients without increased morbidity. The low rate of deep wound infections could be related to the skeletonized technique of internal thoracic artery harvesting.

Aged↗

UVB radiation prevents skeleton growth and stimulates the expression of stress markers in sea urchin embryos.

Ozone depletion results in an increased flux of biologically damaging radiations reaching the earth. Although ultraviolet (UV) penetration is attenuated by the seawater, harmful effects can be still observed at low depths where sea urchin embryos are living. We have used Paracentrotus lividus embryos to study the impacts of UV radiation on their development. Blastula cultures were exposed to different doses of UVB (312 nm) radiations and the resulting endpoint effects were evaluated in terms of embryonic morphological abnormalities, variations in specific gene expression, and changes in the levels of stress proteins. We found that embryos were moderately sensitive to 50 J/m2 UVB radiation; an increase in the number of developmentally delayed and malformed embryos was detected when increasing doses, up to 1000 J/m2, were used. Major developmental defects, observed 24 and 48 h after exposure, consisted in the failure of skeleton elongation and patterning. Accordingly, we found a reduction in the number of primary mesenchyme cells that expressed Pl-SM30, a gene coding for one of the specific matrix proteins of the skeleton. The morphological effects observed 1, 24, and 48 h after exposure were correlated with a dose-dependent increase in the level and in the activation of two recognized stress markers, namely hsp70 and p38 MAPk, respectively, consistent with their role in mediating cellular response to stress and suggesting a function in embryo survival.

Abnormalities, Radiation-Induced↗

Magnetic resonance imaging of the axial skeleton in rheumatoid disease.

The axial skeleton is a target for both spondyloarthritis and rheumatoid arthritis. While conventional radiography allows the clear documentation of the late stages of inflammatory changes, magnetic resonance imaging (MRI) is sensitive enough to depict early inflammatory lesions. It is, therefore, of particular importance for radiologists and clinicians to know the MRI appearances of inflammatory changes of the axial skeleton in rheumatoid diseases. Typical lesions in ankylosing spondylitis and related conditions comprise spondylitis (Romanus lesion), spondylodiscitis (Andersson lesion), arthritis of the apophyseal joints, the costovertebral and costotransverse joints, and insufficiency fractures of the ankylosed vertebral spine (non-inflammatory type of Andersson lesion). Sacroiliitis is associated with chronic changes such as sclerosis, erosions, transarticular bone bridges, periarticular accumulation of fatty tissue and ankylosis. In addition, acute findings include capsulitis, juxta-articular osteitis and the enhancement of the joint space after contrast medium administration. Another important sign of spondyloarthritis is enthesitis, which affects the interspinal and supraspinal ligaments of the vertebral spine and the interosseous ligaments in the retroarticular space of the sacroiliac joints. The main site of manifestation of spinal involvement in rheumatoid arthritis is the cervical spine. Typical changes are the destruction of the atlantoaxial complex by pannus tissue with subsequent atlantoaxial subluxation, basilar impression and erosion of the dens axis. Changes in the lower segments of the cervical spine are destruction of the apophyseal joints resulting in the so-called stepladder phenomenon. Because of the uniform response of the discovertebral complex to different noxae, a number of different conditions must be distinguished on the basis of the patient's clinical findings and history in combination with their imaging appearance. These conditions comprise degenerative disc disease, septic spondylodiscitis, Scheuermann's disease, Paget's disease and diffuse idiopathic skeletal hyperostosis (DISH).

Humans↗

Mechanosensitivity of the rat skeleton decreases after a long period of loading, but is improved with time off.

After the initial adaptation to large mechanical loads, it appears as though the skeleton's responsiveness to exercise begins to wane. To counteract the waning effects of long-term mechanical loading, "time off" may be needed to improve the responsiveness of bone cells to future mechanical signals and reinitiate bone formation. The aim of this study was to determine whether bone becomes less sensitive to long-term mechanical loading and whether time off is needed to improve mechanosensitivity. Fifty-seven female Sprague-Dawley rats (7-8 months of age) were randomized to one of following groups: Group 1 loading was applied for 5 weeks followed by 10 weeks of time off (1 x 5); Group 2 loading was applied for 5 weeks, followed by time off for 5 weeks and loading again for 5 weeks (2 x 5); Group 3 loading was applied continuously for 15 weeks (3 x 5); Group 4 age-matched control group; and Group 5 baseline control group. An axial load was applied to the right ulna for 360 cycles/day, at 2 Hz, 3 days/week at 15 N. At the end of the intervention, all three loaded groups showed similar increases in bone mass, cortical area, and I(MIN) in response to mechanical loading(.) Bone formation rate of the loaded ulna was increased in the first 5 weeks of loading for all three loaded groups; however, during the last 5 weeks, it was only significantly increased in the group that had time off (2 x 5) (P < 0.05). The group that had time off (2 x 5) also showed greater improvements in work to failure compared to the group loaded for 5 weeks (1 x 5) and the entire 15 weeks (3 x 5). A second experiment showed that the waning effect of long-term loading on the skeleton is not a result of aging. In conclusion, mechanical loading of the rat ulna results in large improvements in bone formation during the first 5 weeks of loading, but continual loading decreases the osteogenic response. Having time off increases bone formation and improves the resistance to fracture.

Animals↗