Dysregulation of the alternative pathway (AP) of the complement system is a significant contributor to age-related macular degeneration (AMD), a primary cause of irreversible vision loss worldwide. ...Here, we assess the contribution of the liver-produced complement factor H-related 4 protein (FHR-4) to AMD initiation and course of progression. We show that FHR-4 variation in plasma and at the primary location of AMD-associated pathology, the retinal pigment epithelium/Bruch's membrane/choroid interface, is entirely explained by three independent quantitative trait loci (QTL). Using two distinct cohorts composed of a combined 14,965 controls and 20,741 cases, we ascertain that independent QTLs for FHR-4 are distinct from variants causally associated with AMD, and that FHR-4 variation is not independently associated with disease. Additionally, FHR-4 does not appear to influence AMD progression course among patients with disease driven predominantly by AP dysregulation. Modulation of FHR-4 is therefore unlikely to be an effective therapeutic strategy for AMD.
Familial partial lipodystrophy, Dunnigan type (FPLD), is a rare autosomal dominant genetic disorder characterized by gradual loss of sc fat from the extremities, commencing at the time of puberty. ...Excess fat deposition may occur in the face and neck area. Limited information is available about adipose tissue distribution in patients with FPLD. To investigate whether there is a unique pattern of fat distribution in both affected men and women with FPLD, we performed whole-body magnetic resonance imaging in one male and three female patients from two pedigrees. Magnetic resonance imaging studies confirmed the clinical findings of near-total absence of sc fat from all extremities. Reduction in sc adipose tissue from the truncal area was more prominent anteriorly than posteriorly. Increased fat stores were observed in the neck and face. Intermuscular adipose tissue in the extremities and pelvic area were subjectively increased. Intraabdominal and intrathoracic adipose tissue was not reduced. Bone marrow fat, as well as mechanical adipose tissue, was present in normal amounts. The pattern of fat distribution in the male and females was similar. We conclude that FPLD results in a characteristic absence of sc fat from the extremities, with preservation of intermuscular fat stores.
We report four patients with "dropped head syndrome," a recently described nonprogressive myopathy characterized by severe neck extensor weakness. This relatively benign condition may be confused ...with more ominous neuromuscular disorders that also present with prominent neck weakness. We compared clinical and laboratory data from the patients with dropped head syndrome with findings from patients with head drop caused by other neuromuscular conditions. Patients with "isolated neck extensor myopathy," a term we prefer to "dropped head syndrome," could be readily identified with electrophysiologic, radiographic, and histologic studies.
Autosomal recessive, complete TYK2 deficiency was previously described in a patient (P1) with intracellular bacterial and viral infections and features of hyper-IgE syndrome (HIES), including atopic ...dermatitis, high serum IgE levels, and staphylococcal abscesses. We identified seven other TYK2-deficient patients from five families and four different ethnic groups. These patients were homozygous for one of five null mutations, different from that seen in P1. They displayed mycobacterial and/or viral infections, but no HIES. All eight TYK2-deficient patients displayed impaired but not abolished cellular responses to (a) IL-12 and IFN-α/β, accounting for mycobacterial and viral infections, respectively; (b) IL-23, with normal proportions of circulating IL-17(+) T cells, accounting for their apparent lack of mucocutaneous candidiasis; and (c) IL-10, with no overt clinical consequences, including a lack of inflammatory bowel disease. Cellular responses to IL-21, IL-27, IFN-γ, IL-28/29 (IFN-λ), and leukemia inhibitory factor (LIF) were normal. The leukocytes and fibroblasts of all seven newly identified TYK2-deficient patients, unlike those of P1, responded normally to IL-6, possibly accounting for the lack of HIES in these patients. The expression of exogenous wild-type TYK2 or the silencing of endogenous TYK2 did not rescue IL-6 hyporesponsiveness, suggesting that this phenotype was not a consequence of the TYK2 genotype. The core clinical phenotype of TYK2 deficiency is mycobacterial and/or viral infections, caused by impaired responses to IL-12 and IFN-α/β. Moreover, impaired IL-6 responses and HIES do not appear to be intrinsic features of TYK2 deficiency in humans.
Coherent X-ray diffraction with a convergent beam Chapman, H. N.; Bajt, S.; Li, C. ...
Acta crystallographica. Section A, Foundations and advances,
08/2023, Letnik:
79, Številka:
a2
Journal Article
To assess correlations between muscle edema on magnetic resonance (MR) images and clinical indexes of muscle injury in delayed-onset muscle soreness (DOMS) produced by submaximal exercise protocols.
...Sixteen subjects performed 36 elbow flexions ("biceps curls") at one of two submaximal workloads that emphasized eccentric contractions. Changes in MR imaging findings, plasma levels of creatine kinase, and pain scores were correlated.
Both exercise protocols produced DOMS in all subjects. The best correlation was between change in creatine kinase level and volume of muscle edema on MR images, regardless of the workload. Correlations tended to be better with the easier exercise protocol.
Whereas many previous studies of DOMS focused on intense exercise protocols to ensure positive results, the present investigation showed that submaximal workloads are adequate to produce DOMS and that correlations between conventionally measured indexes of injury may be enhanced at lighter exercise intensities.
Cerebral infarction in eclampsia Zeeman, Gerda G; Fleckenstein, James L; Twickler, Diane M ...
American journal of obstetrics and gynecology,
03/2004, Letnik:
190, Številka:
3
Journal Article
Recenzirano
This study was undertaken to characterize the neuroimaging findings of cerebral edema associated with eclamptic seizures by use of diffusion-weighted magnetic resonance imaging (MRI).
During the ...3-year period ending March 2002, 27 nulliparous women with eclampsia were evaluated with diffusion-weighted MRI and apparent diffusion coefficient mapping. Those with findings of restricted diffusion suggestive of cytotoxic edema underwent neuroimaging again 6 weeks post partum.
All but 2 of these 27 women (93%) had reversible vasogenic edema. Six were also found to have areas of cytotoxic edema consistent with cerebral infarction. Five of these 6 women had persistent imaging findings of infarction when studied post partum, however, without clinical neurologic deficits.
The spectrum of cerebral lesions in eclampsia as seen with MRI varies from initially reversible areas of vasogenic edema that may progress to cytotoxic edema and infarction in up to a fourth of women.
Because determination of neurologic integrity after severe limb trauma is crucial in patient care, the authors assessed magnetic resonance (MR) imaging as a tool to map denervated motor units of ...skeletal muscle in patients with traumatic peripheral neuropathy. Denervation was confirmed in 22 patients with use of electromyography, surgery, or both. MR imaging was performed with moderately T1- and T2-weighted spin-echo and short-tau inversion-recovery (STIR) sequences. MR imaging was unreliable in depicting acute denervation. Muscles of patients with subacute denervation had prolonged T1 and T2, which contributed to conspicuous hyperintensity on STIR images. Chronically denervated muscles showed marked atrophy, variable changes on STIR images, and conspicuous fatty infiltration on T1-weighted images. Normal variants in motor unit anatomy were seen in denervated muscle volumes outside the expected distribution of the injured nerve. MR imaging is promising for the noninvasive mapping and monitoring of denervated muscle in subacute and chronic phases of peripheral neuropathy.
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