Organotypic vasculature Augustin, Hellmut G.; Koh, Gou Young
Science (American Association for the Advancement of Science),
08/2017, Letnik:
357, Številka:
6353
Journal Article
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Blood vessels form one of the body's largest surfaces, serving as a critical interface between the circulation and the different organ environments. They thereby exert gatekeeper functions on tissue ...homeostasis and adaptation to pathologic challenge. Vascular control of the tissue microenvironment is indispensable in development, hemostasis, inflammation, and metabolism, as well as in cancer and metastasis. This multitude of vascular functions is mediated by organ-specifically differentiated endothelial cells (ECs), whose cellular and molecular heterogeneity has long been recognized. Yet distinct organotypic functional attributes and the molecular mechanisms controlling EC differentiation and vascular bed-specific functions have only become known in recent years. Considering the involvement of vascular dysfunction in numerous chronic and life-threatening diseases, a better molecular understanding of organotypic vasculatures may pave the way toward novel angiotargeted treatments to cure hitherto intractable diseases. This Review summarizes recent progress in the understanding of organotypic vascular differentiation and function.
Schizophrenia is a devastating neuropsychiatric syndrome associated with distributed brain dysconnectivity that may involve large-scale thalamo-cortical systems. Incomplete characterization of ...thalamic connectivity in schizophrenia limits our understanding of its relationship to symptoms and to diagnoses with shared clinical presentation, such as bipolar illness, which may exist on a spectrum. Using resting-state functional magnetic resonance imaging, we characterized thalamic connectivity in 90 schizophrenia patients versus 90 matched controls via: (1) Subject-specific anatomically defined thalamic seeds; (2) anatomical and data-driven clustering to assay within-thalamus dysconnectivity; and (3) machine learning to classify diagnostic membership via thalamic connectivity for schizophrenia and for 47 bipolar patients and 47 matched controls. Schizophrenia analyses revealed functionally related disturbances: Thalamic over-connectivity with bilateral sensory-motor cortices, which predicted symptoms, but thalamic under-connectivity with prefrontal-striatal-cerebellar regions relative to controls, possibly reflective of sensory gating and top-down control disturbances. Clustering revealed that this dysconnectivity was prominent for thalamic nuclei densely connected with the prefrontal cortex. Classification and cross-diagnostic results suggest that thalamic dysconnectivity may be a neural marker for disturbances across diagnoses. Present findings, using one of the largest schizophrenia and bipolar neuroimaging samples to date, inform basic understanding of large-scale thalamo-cortical systems and provide vital clues about the complex nature of its disturbances in severe mental illness.
•fALFF was used to study ECT response in MDD patients.•The pairwise comparisons were made between healthy controls, pre- and post-ECT MDD.•The antidepressant and side effects were related to the ...changes in specific regions.
Electroconvulsive therapy (ECT) is an important treatment option for patients with major depressive disorder (MDD). However, the mechanisms of ECT in MDD are still unclear.
Twenty-four patients with severe MDD and 14 healthy controls were enrolled in this study. Eight ECT sessions were conducted for MDD patients using brief-pulse square-wave signal at bitemporal locations. To investigate the regional cerebral blood flow in MDD patients before and after ECT treatments by resting-state functional magnetic resonance imaging (rs-fMRI), the patients were scanned twice (before the first ECT and after the eighth ECT) for data acquisition. Afterward, we adopted fractional amplitude of low-frequency fluctuations (fALFF) to assess the alterations of regional brain activity.
Compared with healthy controls, the fALFF in the cerebellum lobe, parahippocampal gyrus, fusiform gyrus, anterior cingulate gyrus, and thalamus in MDD patients before ECT (pre-ECT) was significantly increased. In another comparison, the fALFF in the cerebellum anterior lobe, fusiform gyrus, insula, parahippocampal gyrus, middle frontal gyrus, and inferior frontal gyrus in pre-ECT patients was significantly greater than the post-ECT fALFF.
Only two rs-fMRI scans were conducted at predefined times: before the first and after the eighth ECT treatment. More scans during the ECT sessions would yield more information. In addition, the sample size in this study was limited. The number of control subjects was relatively small. A larger number of subjects would produce more robust findings.
The fALFF of both healthy controls and post-ECT patients in cerebellum anterior lobe, fusiform gyrus, and parahippocampal gyrus is significantly lower than the fALFF of pre-ECT patients. This finding demonstrates that ECT treatment is effective on these brain areas in MDD patients.
BACKGROUND:Reports of more than two cutaneous perforator angiosome territories being raised successfully in distally based sural flaps are appearing in the literature. Previous anatomical studies ...have noted that cutaneous arteries, connected by true anastomosis without change in caliber, frequently parallel cutaneous nerves.
METHODS:Twenty-four (48 sides) total body lead oxide cadaver injection studies, including seven arterial and two venous neurovascular, were examined, and the results were compared with clinical thermography in Part II.
RESULTS:Long branches of cutaneous perforators, connected in a series by true anastomoses, paralleled at variable distances the main trunks of cutaneous nerves in the head, neck, torso, and upper and lower extremities. Specifically, in the leg, an average of 3.2 true anastomoses (range, 1 to 5) connected perforators that paralleled the sural nerve on the back of the calf; and 2.5 (range, 1 to 4) connected perforators on the medial side of the leg. These vascular freeways were paralleled by the short and long saphenous veins, respectively.
CONCLUSIONS:True anastomoses frequently connect skin perforators that course in parallel with cutaneous nerves and veins. They provide an explanation for the long viable flaps noted in the leg, and it will be shown in Part II that they can be detected preoperatively with thermography.
Mammalian organs continually exchange metabolites via circulation, but systems-level analysis of this shuttling process is lacking. Here, we compared, in fasted pigs, metabolite concentrations in ...arterial blood versus draining venous blood from 11 organs. Greater than 90% of metabolites showed arterial-venous differences across at least one organ. Surprisingly, the liver and kidneys released not only glucose but also amino acids, both of which were consumed primarily by the intestine and pancreas. The liver and kidneys exhibited additional unexpected activities: liver preferentially burned unsaturated over more atherogenic saturated fatty acids, whereas the kidneys were unique in burning circulating citrate and net oxidizing lactate to pyruvate, thereby contributing to circulating redox homeostasis. Furthermore, we observed more than 700 other cases of tissue-specific metabolite production or consumption, such as release of nucleotides by the spleen and TCA intermediates by pancreas. These data constitute a high-value resource, providing a quantitative atlas of inter-organ metabolite exchange.
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•A systems-level atlas of organ-specific metabolite production and consumption•700 quantitative measurements of organ-specific uptake or excretion•Kidneys burn circulating citrate and net-oxidize lactate to pyruvate•Liver preferentially consumes unsaturated over saturated fatty acids
Using metabolomics in the arterial blood and draining veins of 11 organs in fasted pigs, Jang et al. map more than 700 cases of organ-specific metabolite production or consumption. The resulting data resource provides a blueprint for the integrative function of mammalian metabolism.
In a significant fraction of breast cancer patients, distant metastases emerge after years or even decades of latency. How disseminated tumour cells (DTCs) are kept dormant, and what wakes them up, ...are fundamental problems in tumour biology. To address these questions, we used metastasis assays in mice and showed that dormant DTCs reside on microvasculature of lung, bone marrow and brain. We then engineered organotypic microvascular niches to determine whether endothelial cells directly influence breast cancer cell (BCC) growth. These models demonstrated that endothelial-derived thrombospondin-1 induces sustained BCC quiescence. This suppressive cue was lost in sprouting neovasculature; time-lapse analysis showed that sprouting vessels not only permit, but accelerate BCC outgrowth. We confirmed this surprising result in dormancy models and in zebrafish, and identified active TGF-β1 and periostin as tumour-promoting factors derived from endothelial tip cells. Our work reveals that stable microvasculature constitutes a dormant niche, whereas sprouting neovasculature sparks micrometastatic outgrowth.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
There are few data on the cerebral organization of motor aspects of speech production and the pathomechanisms of dysarthric deficits subsequent to brain lesions and diseases. The authors used fMRI to ...further examine the neural basis of speech motor control.
In eight healthy volunteers, fMRI was performed during syllable repetitions synchronized to click trains (2 to 6 Hz; vs a passive listening task). Bilateral hemodynamic responses emerged at the level of the mesiofrontal and sensorimotor cortex, putamen/pallidum, thalamus, and cerebellum (two distinct activation spots at either side). In contrast, dorsolateral premotor cortex and anterior insula showed left-sided activation. Calculation of rate/response functions revealed a negative linear relationship between repetition frequency and blood oxygen level-dependent (BOLD) signal change within the striatum, whereas both cerebellar hemispheres exhibited a step-wise increase of activation at approximately 3 Hz. Analysis of the temporal dynamics of the BOLD effect found the various cortical and subcortical brain regions engaged in speech motor control to be organized into two separate networks (medial and dorsolateral premotor cortex, anterior insula, and superior cerebellum vs sensorimotor cortex, basal ganglia, and inferior cerebellum).
These data provide evidence for two levels of speech motor control bound, most presumably, to motor preparation and execution processes. They also help to explain clinical observations such as an unimpaired or even accelerated speaking rate in Parkinson disease and slowed speech tempo, which does not fall below a rate of 3 Hz, in cerebellar disorders.
Abstract The aim of this study was to analyze and describe the intrapapillary capillary loops (IPCL), which are a feature of early oral neoplastic lesions, using a narrowband imaging (NBI) system. ...Forty-one patients (26 men, 15 women; mean age, 52.34 years; range, 23–83 years) presenting with non-neoplastic or neoplastic lesions, and normal cases, were examined using the prototype Evis Lucera Spectrum (Olympus Co.). The images were analyzed and an IPCL classification was devised. All normal cases ( n = 10) had regularly distributed capillary loops of the same shape (type I). Non-neoplastic lesions ( n = 8) had mild changes of the capillary loops (types II and III) and neoplastic lesions ( n = 23) were irregularly distributed and had several loop shapes (types III and IV). The microvascular organization of non-neoplastic lesions was notably different from that of neoplastic lesions. A brownish area was found in five cases of early carcinoma. The narrowband imaging system is a potential approach for clinically analyzing microvascular organization and IPCL. It could be useful for diagnosing oral squamous cell carcinoma at an earlier stage and for determining the margin of resection.
BACKGROUND:The first successful free vascularized bone flap was performed on June 1, 1974 (and reported in 1975), using the fibula. This was followed by the iliac crest based on the superficial ...circumflex iliac artery in 1975 and then the deep circumflex iliac artery in 1978.
METHODS:A total of 384 transfers using fibula (n = 198), iliac crest (n = 180), radius (n = 4), rib (n = 1), and metatarsal (n = 1) were used between June of 1974 and June of 2014 for reconstruction of the mandible (n = 267), maxilla (n = 20), clavicle (n = 1), humerus (n = 8), radius and ulna (n = 21), carpus (n = 3), pelvis (n = 2), femur (n = 11), tibia (n = 47), and foot bones (n = 4). Indications were tumor ablation (n = 286), trauma (n = 84), osteomyelitis (n = 2), and the congenital deformities hemifacial microsomia (n = 2) and pseudarthrosis of the tibia (n = 9) and ulna (n = 1).
RESULTS:Successful transfer was achieved in 95 percent of patients. Union varied with the recipient bone, from 6 to 8 weeks in the jaw, 2 to 3 months in the upper limb, and 3 to 4 months in the femur and tibia. Union was fastest with iliac crest. The fibula provided easier dissection; it could be raised on either peroneal or anterior tibial vessels; the skin flap could be designed distally; it could be placed centrally in the medullary cavity of long bones; and hairline stress fracture in the lower limb frequently preceded rapid subperiosteal hypertrophy. The fibula lacks sufficient height for osseointegration, whereas iliac crest is ideal. Osteotomies of either bone are possible to straighten or increase curvature.
CONCLUSIONS:The fibula is best for long bone or angle-to-angle jaw reconstruction, especially in edentulous patients. Iliac crest is best for hemimandible, curved bones (pelvis, carpus, and metacarpus), and as an alternative for short, straight, 6- to 8-cm-long bone defects.
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