The effects of erythropoetic activity and iron burden on hepcidin expression in patients with thalassemia major

Hepcidin production is homeostatically regulated by iron stores, anemia and hypoxia. We evaluated the effect of iron overload and of ineffective erythropoeisis on hepcidin expression in patients with thalassemia major. Liver hepcidin mRNA levels correlated with hemoglobin concentration and inversely correlated with serum transferrin receptor, erythropoietin and non-transferrin-bound iron. They did not correlate with indices of iron load. Urinary hepcidin levels were disproportionably suppressed in regards to iron burden. We conclude that hepcidin expression is regulated mainly by increased erythropoietic activity rather than by iron load and that hepcidin plays a central regulatory role in iron circulation and iron toxicity in patients with thalassemia.     

Establishment of human T-cell leukemia virus type I T-cell lymphomas in severe combined immunodeficient mice

Human T-cell leukemia virus type I (HTLV-I) is recognized as the etiologic agent of adult T-cell leukemia (ATL), a disease endemic in certain regions of southeastern Japan, Africa, and the Caribbean basin. Although HTLV-I can immortalize T lymphocytes in culture, factors leading to tumor progression after HTLV-I infection remain elusive. Previous attempts to propagate the ATL tumor cells in animals have been unsuccessful. Severe combined immunodeficient (SCID) mice have previously been used to support the survival of human lymphoid cell populations when inoculated with human peripheral blood lymphocytes (PBL). SCID mice were injected intraperitoneally with PBL from patients diagnosed with ATL, HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), or from asymptomatic HTLV-I-seropositive patients. Many of these mice become persistently infected with HTLV-I. Furthermore, after human reconstitution was established in these mice, HTLV-I-infected cells displayed a proliferative advantage over uninfected human cells. Lymphoblastic lymphomas of human origin developed in animals injected with PBL from two ATL patients. The tumor cells represented outgrowth of the original ATL leukemic clone in that they had monoclonal or oligoclonal integrations of the HTLV-I provirus identical to the leukemic clone and predominantly expressed the cell surface markers, CD4 and CD25. In contrast, cell lines derived by HTLV immortalization of T cells in vitro did not persist or form tumors when inoculated into SCID mice, indicating differences between in vitro immortalized cells and ATL leukemic cells. This system represents the first small animal model to study HTLV-I tumorigenesis in vivo.     

Population receptive field analysis of the primary visual cortex complements perimetry in patients with homonymous visual field defects

Injury to the primary visual cortex (V1) typically leads to loss of conscious vision in the corresponding, homonymous region of the contralateral visual hemifield (scotoma). Several studies suggest that V1 is highly plastic after injury to the visual pathways, whereas others have called this conclusion into question. We used functional magnetic resonance imaging (fMRI) to measure area V1 population receptive field (pRF) properties in five patients with partial or complete quadrantic visual field loss as a result of partial V1+ or optic radiation lesions. Comparisons were made with healthy controls deprived of visual stimulation in one quadrant [“artificial scotoma” (AS)]. We observed no large-scale changes in spared-V1 topography as the V1/V2 border remained stable, and pRF eccentricity versus cortical-distance plots were similar to those of controls. Interestingly, three observations suggest limited reorganization: (i) the distribution of pRF centers in spared-V1 was shifted slightly toward the scotoma border in 2 of 5 patients compared with AS controls; (ii) pRF size in spared-V1 was slightly increased in patients near the scotoma border; and (iii) pRF size in the contralesional hemisphere was slightly increased compared with AS controls. Importantly, pRF measurements yield information about the functional properties of spared-V1 cortex not provided by standard perimetry mapping. In three patients, spared-V1 pRF maps overlapped significantly with dense regions of the perimetric scotoma, suggesting that pRF analysis may help identify visual field locations amenable to rehabilitation. Conversely, in the remaining two patients, spared-V1 pRF maps failed to cover sighted locations in the perimetric map, indicating the existence of V1-bypassing pathways able to mediate useful vision.Cortical damage of the visual pathway often results from posterior or middle cerebral artery infarcts, hemorrhages, and other brain injuries. The most common visual cortex lesions involve the primary visual cortex (V1), the chief relayer of visual information to higher visual areas. Damage to area V1 or its primary inputs leads to the loss of conscious vision in the corresponding region of the contralateral visual hemifield, producing a dense contralateral scotoma that often covers a hemifield (hemianopia) or a single visual field quadrant (quadrantanopia).A much-debated issue is whether the adult V1 is able to reorganize after injury. Reorganization refers to long-term changes in the neuronal circuit (1) and generally requires the growth of new anatomic connections or a permanent change in the strength of existing connections. Several studies report significant remapping in area V1 of patients suffering from macular degeneration and other retinal lesions (2–12). The extent of this remapping has recently been called into question, however (1, 13–19). Less is known about how the visual system remaps to cover the visual field after injury to area V1 or its input projection from the lateral geniculate nucleus (LGN). Enlarged receptive fields have been found in areas surrounding chronic V1 lesions in cats (20–22), and visual point spread functions were seen to enlarge over time in the areas surrounding focal V1 lesions in kittens (23). Smaller, short-term changes (2 d after the lesion) have been reported as well (24). As expected, reorganization is more extensive in young animals (23, 25) compared with adults (26). A change in the balance between excitation and inhibition may underlie this functional reorganization (27–31).In humans, V1 injury is typically followed by a brief period of spontaneous recovery, which rarely lasts beyond 6 mo (32). Whether this recovery is the result of true visual system plasticity or is related to the gradual resolution of perilesional edema and general clinical improvement of the patients is unclear. A recent study in an adult human subject suggested that large-scale reorganization occurs in area V1 after partial deafferentiation by an optic radiation lesion (33); however, quantitative measurements were not performed. To date, there has been no systematic study in humans investigating how spared V1 cortex covers the visual field after chronic V1 injury. The present work is an effort in this direction.We used the population receptive field (pRF) mapping method (34) to study how spared area V1 covers the visual field after chronic injury in five adult human subjects suffering from partial or complete quadrantanopia. Our findings suggest that there is at best a limited degree of reorganization in the spared part of area V1 after partial V1 injury. Interestingly, the pattern of coverage of the visual field measured in spared V1 cortex by functional magnetic resonance imaging (fMRI) typically does not match predictions derived from perimetry maps. Identifying the patterns of mismatch and how they relate to the capacity of early visual areas to reorganize after injury will eventually allow the adoption of more rational strategies for visual rehabilitation.     

云南边境地区氯喹及与青蒿琥酯伍用治疗前后恶性疟原虫pfcrt 和pfmdr1抗药性有关基因点突变的变化特征

目的　了解氯喹单用及与青蒿琥脂伍用治疗恶性疟前后 ,pfcrt和 pfmdr1抗药性有关基因的点突变变化特征。　 方法　使用PCR RFLP技术检测基因点突变。　结果　氯喹及与青蒿琥脂伍用治疗前后的所有样本都发现有恶性疟原虫pfcrt基因氨基酸编码 76突变为苏氨酸的特征。但是 ,氯喹治疗前 ,5 0 % pfmdr1基因氨基酸编码 86为天冬酰氨酸 (野生型 ) ,而剩余的 5 0 %为野生型和突变型 (苏氨酸 )的特征。氯喹治疗后 ,在 18个复燃的病例中 ,83 .3 %的 pfmdr1基因 86位点为野生型 ,剩余的 16.7%是混合型。氯喹与青蒿琥脂伍用治疗前 ,3个样本携带混合型基因型 ,剩余的 (86% )为野生型 ,但治疗后 ,所有样本只携带野生型。　结论　这些结果可能支持这样的假说 :pfcrt基因突变起主导作用 ,但 pfmdr1基因突变增强了氯喹抗药性的效果。     

New Interview and Observation Measures of the Broader Autism Phenotype: Impressions of Interviewee Measure

A 20 item observational measure of social functioning, the Impression of Interviewee rating scale, is one of three measures devised to assess the broader autism phenotype. The sample studied included families containing at least two individuals with autism spectrum disorder; observations were undertaken by the researcher who interviewed the subject. An exploratory factor analysis suggested a single factor was most appropriate (Cronbach’s α of 0.78). There was a modest but significant retest correlation of 0.42. Correlations between live ratings and blind consensus ratings of vignettes were high (0.93). Correlations with the interview measures were moderate but statistically significant. In conclusion, the observational scale provides a promising start but further work is required before general use can be recommended.