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91.
Peer Arts Jessica Garland Alicia B. Byrne Tristan S.E. Hardy Milena Babic Jinghua Feng Paul Wang Thuong Ha Sarah L. King‐Smith Andreas W. Schreiber April Crawford Nick Manton Lynette Moore Christopher P. Barnett Hamish S. Scott 《American journal of medical genetics. Part A》2020,182(5):1273-1277
Autosomal dominant (de novo) mutations in PBX1 are known to cause congenital abnormalities of the kidney and urinary tract (CAKUT), with or without extra‐renal abnormalities. Using trio exome sequencing, we identified a PBX1 p.(Arg107Trp) mutation in a deceased one‐day‐old neonate presenting with CAKUT, asplenia, and severe bilateral diaphragmatic thinning and eventration. Further investigation by droplet digital PCR revealed that the mutation had occurred post‐zygotically in the father, with different variant allele frequencies of the mosaic PBX1 mutation in blood (10%) and sperm (20%). Interestingly, the father had subclinical hydronephrosis in childhood. With an expected recurrence risk of one in five, chorionic villus sampling and prenatal diagnosis for the PBX1 mutation identified recurrence in a subsequent pregnancy. The family opted to continue the pregnancy and the second affected sibling was stillborn at 35 weeks, presenting with similar severe bilateral diaphragmatic eventration, microsplenia, and complete sex reversal (46, XY female). This study highlights the importance of follow‐up studies for presumed de novo and low‐level mosaic variants and broadens the phenotypic spectrum of developmental abnormalities caused by PBX1 mutations. 相似文献
92.
Attenuated LTP in hippocampal dentate gyrus neurons of mice deficient in the PAF receptor 总被引:8,自引:0,他引:8
Platelet-activating factor (PAF), a bioactive lipid (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) derived from phospholipase A(2) and other pathways, has been implicated in neural plasticity and memory formation. Long-term potentiation (LTP) can be induced by the application of PAF and blocked by a PAF receptor (PAF-R) inhibitor in the hippocampal CA1 and dentate gyrus. To further investigate the role of PAF in synaptic plasticity, we compared LTP in dentate granule cells from hippocampal slices of adult mice deficient in the PAF-R and their age-matched wild-type littermates. Whole cell patch-clamp recordings were made in the current-clamp mode. LTP in the perforant path was induced by a high-frequency stimulation (HFS) and defined as >20% increase above baseline of the amplitude of excitatory postsynaptic potentials (EPSPs) from 26 to 30 min after HFS. HFS-induced enhancement of the EPSP amplitude was attenuated in cells from the PAF-R-deficient mice (163 +/- 14%, mean +/- SE; n = 32) when compared with that in wild-type mice (219 +/- 17%, n = 32). The incidence of LTP induction was also lower in the cells from the deficient mice (72%, 23 of 32 cells) than in the wild-type mice (91%, 29 of 32 cells). Using paired-pulse facilitation as a synaptic pathway discrimination, it appeared that there were differences in LTP magnitudes in the lateral perforant path but not in the medial perforant path between the two groups. BN52021 (5 microM), a PAF synaptosomal receptor antagonist, reduced LTP in the lateral path in the wild-type mice. However, neither BN52021, nor BN50730 (5 microM), a microsomal PAF-R antagonist, reduced LTP in the lateral perforant path in the receptor-deficient mice. These data provide evidence that PAF-R-deficient mice are a useful model to study LTP in the dentate gyrus and support the notion that PAF actively participates in hippocampal synaptic plasticity. 相似文献
93.
S R Bloom A V Edwards R N Hardy K Malinowska M Silver 《The Journal of physiology》1975,253(1):135-155
A number of cardiovascular and endocrine responses which occur during and after feeding in the unweaned calf are described. 2. There was a substantial increase in both heart rate and mean aortic blood pressure during feeding in these animals. This occurred within the first few seconds and persisted throughout the period of ingestion. 3. The concentrations of glucose, insulin and gastrin in arterial plasma rose abruptly during, or immediately after, feeding and elevated values persisted for at least 2 hr. A transient increase in glucagon concentration was also observed. In contrast, feeding appeared to produce no immediate rise in enteroglucagon concentration. 4. The adrenal output of glucocorticoids rose transiently in response to feeding but that of catecholamines was unaffected. 5. Cardiovascular responses to feeding were also examined in other species. In unweaned kids the changes were essentially similar to those observed in the calf but were less pronounced. In lambs a persistent hypertension occurred which was associated with a brief initial tachycardia. In adult dogs ingestion of solid food also caused tachycardia but although the aortic blood pressure rose for a short period at the beginning of feeding, hypotension developed thereafter. 6. The possibility that both the cardiovascular and endocrine responses, which occur during or immediately after feeding, are mediated by the autonomic nervous system is discussed. 相似文献
94.
A review of 1H nuclear magnetic resonance relaxation in pathology: are T1 and T2 diagnostic? 总被引:3,自引:0,他引:3
The longitudinal (T1) and transverse (T2) proton (1H) nuclear magnetic resonance (NMR) relaxation times of pathological human and animal tissues in the frequency range 1-100 MHz are archived, reviewed, and analyzed as a function of tissue of origin, NMR frequency, temperature, species, and in vivo versus in vitro status. T1 data from specific disease states of the bone, brain, breast, kidney, liver, muscle, pancreas, and spleen can be characterized by simple dispersions of the form T1 = AvB in the range 1-100 MHz with A and B empirically determined pathology-dependent constants. Pathological tissue T2 values are essentially independent of NMR frequency. Raw relaxation data, best-fit T1 parameters A and B, and the mean T2 values, are tabulated along with standard deviations and sample size to establish the normal range of pathological tissue relaxation times applicable to NMR imaging or in vitro NMR examination. Statistical analysis of relaxation data, assumed independent, reveals that most tumor and edematous tissue T1 values and some breast, liver, and muscle tumor T2 values are significantly elevated (p greater than or equal to 0.95) relative to normal, but do not differ significantly from other tumors and pathologies. Statistically significant abnormalities in the T1 values of some brain, breast, and lung tumors, and most pathological tissue T2 values could not, however, be demonstrated in the presence of large statistical errors. Both T1 and T2 in uninvolved tissue from tumor-bearing animals or organs do not demonstrate statistically significant differences from normal when considered as a group, suggesting no appreciable systemic effects associated with the presence of tumors compared to the statistical uncertainty. Statistical prediction analysis for both T1 and T2 indicates that of all the tissues studied, only liver hepatoma can be reliably distinguished from normal liver based on a single T1 measurement (p greater than or equal to 0.95) given the scatter in the current published data. Indeed, data scatter, not easily attributable to temperature, species, in vivo versus in vitro status, the inclusion of implanted or chemical induced tumors, or the possible existence of multiple component relaxation, is recognized as the major factor inhibiting the diagnostic utility of quantitative NMR relaxation measurements. Malignancy indexes that combine T1 and T2 data as a diagnostic indicator suffer similar problems of uncertainty. The literature review reveals a dearth of information on the temperature and frequency dependence of pathological tissue relaxation and the possible existence of multiple relaxation components.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
95.
Isolation and Purification of Treponema pallidum from Syphilitic Lesions in Rabbits 总被引:1,自引:5,他引:1
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Treponema pallidum were extracted from testicular syphilomas of corticosteroid-treated rabbits and purified by differential centrifugation. The steroid therapy allowed a longer holding time for infected rabbits, which produced greater treponeme yields, averaging 1.58 × 1010 treponemes per rabbit. The treatment, which also diminished cellular infiltration and increased the extracellular mucoid material in lesions, produced much cleaner suspensions than preparations from nontreated animals. Most of the treponemes in the purified suspensions were still motile, and none carried demonstrable host immunoglobulin. The preparations were free of recognizable host tissue debris and they contained, on the average, 1.9 × 10−7 μg of protein per treponeme. 相似文献
96.
The effect of adrenalectomy or pharmacological inhibition of adrenocortical function on macromolecule uptake by the new-born rat intestine
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1. Bilateral adrenalectomy in 18-day-old rats resulted in an extension by approximately 4 days of the period during which the villous epithelial cells of the small intestine took up polyvinyl pyrrolidone (PVP) of mean mol. wt. 160,000.2. The eventual termination of PVP uptake (;closure') closely resembled normal closure in control animals: the time course of the decline in uptake and the histological changes indicated that more mature ;PVP-impermeable' cells progressively ascended the villi.3. Injection of Metopirone was ineffective in animals 10 days after birth, but when injected after day 13 caused closure within 3 days.4. Metopirone injection significantly reduced the plasma concentration of corticosterone and caused a marked rise in the plasma concentration of deoxycorticosterone.5. Aminoglutethimide injection also produced precocious closure and had an effect similar to Metopirone on the plasma concentrations of corticosterone and deoxycorticosterone.6. Injection of Metopirone or aminoglutethimide increased the relative adrenal weight compared with control animals. Aminoglutethimide was more effective and caused approximately a 100% increase in adrenal weight. 相似文献
97.
We have previously defined four murine CD4+ peripheral T cell subsets, fractions (Fr.) I – IV, based on expression of the 6C10 and 3G11 determinants (Hayakawa, K. and Hardy, R. R., J. Exp. Med. 1988. 168: 1825). These subsets also show distinctive levels of other cell surface markers: the two minor subsets, Fr. III and Fr. IV, are both CD45RBlow/-, L-selectin (Mel-14)? and CD44hi, characteristic of secondary T cells. The patterns and levels of cytokine production by individual cells in each subset were determined by bioassay for interleukin (IL)-2/IL-4 or IL-4/interferon (IFN)-γ production after anti-CD3 stimulation. Our data revealed that these four phenotypically defined subsets largely coincide with clusters of cells showing uniform distinctive cytokine profiles, i.e. IL-2+/IFN-γ?/IL-4? (Fr. I and Fr. II, L-selectin+), IL-2+/IFN-γ+/IL-4+ (Fr. III, L-selectin?), and IL-2?/IFN-γlow/-/IL-4+ (Fr. IV, L-selectin?). Besides these subsets, an L-selectin-negative cell subfraction within Fr. II appears to represent a transitional population between the IL-2+/IFN-γ?/IL-4? stage and the IL-2+/IFN-γ+/IL-4+ stage. Taken together, these results demonstrate the presence of two IL-4+ secondary T cell subsets with distinct cytokine production patterns, and show that the majority of IL-4+ cells found in healthy adult laboratory mice co-produce IFN-γ, and thus are not typical T helper type 2 cells. 相似文献
98.
Complex and simple coronary artery stenoses: a new way to interpret coronary angiograms based on morphologic features of lesions 总被引:1,自引:0,他引:1
For many years, atherosclerotic coronary artery lesions have been described by angiographers only in terms of location and degree of narrowing. However, it has become apparent that coronary stenoses generally have distinct morphologic features that can be recognized at angiography and that allow them to be classified as either "simple" or "complex" plaques. Complex plaques are those characterized by ulcerated or ruptured surfaces, subintimal hemorrhage, superimposed partially occluding thrombi, recanalized thrombi, or some combination. Pathologic studies have shown a very high frequency of these lesions at sites of total thrombotic occlusion of coronary arteries. Clinical and angiographic studies have demonstrated a high frequency of such lesions in living patients with both unstable angina and acute myocardial infarction. The presence of complex stenoses has also been found to increase the risk of future myocardial infarction. Plaque morphology thus appears to significantly affect the prognosis of patients with coronary disease and should be carefully evaluated in interpretation of all coronary angiograms. 相似文献
99.
Dr. Gurnam S. Basran John G. Hardy Sai P. Woo Ramiah Ramasubramanian Andrew J. Byrne 《European journal of nuclear medicine and molecular imaging》1986,12(8):381-384
Increased lung vascular permeability leading to increased plasma protein extravasation and accumulation (PPA) is a characteristic feature of acute lung injury. Using a previously described technique, PPA was monitored in the lungs of patients with the adult respiratory distress syndrome (ARDS) — an extreme example of acute lung injury in man. An external radiation probe detector was used to monitor the pulmonary accumulation of the plasma protein transferrin radiolabelled in-vivo with 113mIn. Ten patients with ARDS exhibiting increased PPA indices (>1.0x10-3/min) were given an intravenous infusion of terbutaline (7 g/kg) over 30 min. Of the four patients in whom the post-drug PPA indices remained within the ARDS range, none survived, whilst five of the six patients in whom the post-drug PPA indices were reduced to below 1.0x10-3/min survived. PPA indices prior to the administration of terbutaline were not significantly different between the survivor (n=5) and non-survivor (n=5) groups. There was a significant decrease in the PPA indices following terbutaline in survivors (p<0.01) but not in non-survivors. Thus beta-2-agonists in therapeutic doses can inhibit increased lung vascular permeability in man. These findings may have prognostic and therapeutic implication for beta-2-agonists in ARDS. 相似文献
100.