Distinct variants of erythrocyte protein 4.1 inherited in linkage with elliptocytosis and Rh type in three white families

Hereditary elliptocytosis is a heterogeneous disorder resulting from defects in the erythrocyte membrane skeleton. Although some cases of elliptocytosis result from defects in spectrin, the specific structural abnormality has yet to be identified in the majority of cases. Protein 4.1 plays an essential role in erythrocyte membrane physiology, and deficiencies have been implicated in only a few rare cases of elliptocytosis. By using 4.1 immunoblots and a 4.1 radioimmunoassay we identified distinct variants of protein 4.1 in 15 elliptocytic members of three US white families with the Rh-linked form of elliptocytosis. Elliptocytic members of family G were heterozygotes for a low-molecular weight (mol wt) 4.1 variant (65,000 to 68,000 daltons; normal, 80,000) inherited in linkage with the Rz phenotype. Elliptocytic members of family C expressed a simple partial deficiency of protein 4.1 (63% of the normal level) that was inherited in linkage with the r phenotype. Elliptocytic members of family N were heterozygotes for a high-mol wt 4.1 variant (100,000 daltons) also inherited in linkage with the r phenotype. These studies indicate that mutant forms of protein 4.1 are not uncommon in elliptocytosis among whites and that different kindreds probably express different mutations. The observed linkage of elliptocytosis and Rh blood type most likely results from the close proximities of the 4.1 gene (site of the mutation) and the Rh gene, which is located nearby on the short arm of chromosome 1.     

Erythroid failure in Diamond-Blackfan anemia is characterized by apoptosis

Programmed cell death, also known as apoptosis, is frequently initiated when cells are deprived of specific trophic factors. To investigate if accelerated apoptosis contributes to the pathogenesis of Diamond- Blackfan anemia (DBA), a rare pure red blood cell aplasia of childhood, we studied the effect of erythropoietin (epo) deprivation on erythroid progenitors and precursors from the bone marrow of DBA patients as compared with hematologically normal controls. Apoptosis in response to epo deprivation was evaluated by enumeration of colony-forming unit- erythroid (CFU-E)- and burst-forming unit-erythroid (BFU-E)-derived colonies in plasma clot semisolid culture and by the identification of typical DNA oligosomes by gel electrophoresis from marrow mononuclear cells in liquid culture. In all DBA patients there was a marked decrease in CFU-E- and BFU-E-derived colony formation compared with normal controls at comparable time points of epo deprivation, with a complete loss of CFU-E-derived colonies in semisolid culture by 9 hours of epo deprivation versus 48 hours in controls. The BFU-E-derived colony response to epo deprivation displayed a similar pattern of decrement. Apoptotic changes assessed by the presence of characteristic DNA fragmentation began in the absence of epo deprivation and were readily detected within 3 hours of epo deprivation in DBA cultures versus 9 hours in controls. We conclude that DBA is characterized by accelerated apoptosis as measured by the loss of erythroid progenitor clonogenicity and increased progenitor and precursor DNA fragmentation leading to the formation of characteristic oligosomes, consistent with an intrinsic erythroid-progenitor defect in which increased sensitivity to epo deprivation results in erythroid failure.     

薄荷醇与樟脑对烟酰胺的促皮渗透作用的研究

目的:研究薄荷醇和樟脑对烟酰胺透皮吸收的影响。方法:用两室扩散池体外透皮实验装置,以兔皮为屏障,使用不同浓度的薄荷醇和樟脑,测定烟酰胺的透皮百分率。结果:含1％薄荷醇组和含1％樟脑组的烟酰胺透皮百分率无显著增加,而含1％薄荷醇和1％樟脑组,含3％薄荷醇组,含3％樟脑组,含3％薄荷醇和3％樟脑组的烟酰胺透皮百分率明显增加。结论:薄荷醇和樟脑均对烟酰胺有促皮渗透作用,两药作用强度相似,两药使用时具有协同作用。     

神经节苷脂GM1对乙醇引起的神经膜磷脂脂肪酸参入变化的影响

研究神经节苷脂ＧＭ１对乙醇引起的神经膜磷脂的脂肪酸参入变化的影响。使用同位素标记的脂肪酸测定其对神经膜磷脂不同组分的参入率，比较ＧＭ１和乙醇对参入率的影响。慢性乙醇暴露发迹了不饱和脂肪酸「油酸，亚油酸，花生四烯酸和二十二碳六烯酸」参入到旨酰肌醇，磷脂酰丝氨酸和磷脂酰胆碱。     

Exudative macular degeneration and intravitreal triamcinolone: 18 month follow up

Purpose: To evaluate the safety and efficacy of intravitreal triamcinolone after 18 months of follow up in patients with age-related macular degeneration and subfoveal or juxtafoveal choroidal neovascularization considered unsuitable for laser photocoagulation. Methods: Thirty eyes of 28 patients, referred from general eye clinics as well as the private clinic of one of the authors to a hospital-based retinal out-patient clinic, were treated with an intravitreal injection of triamcinolone (4mg). The primary outcome measure was the proportion of eyes with loss of six or more lines on a Bailey-Lovie Chart. The incidence of adverse events associated with treatment was also observed. Results: Of the 20 eyes with initial visual acuity (VA) of 6/60 or better, the vision was maintained (± 1 Bailey-Lovie lines) in 11 eyes (55%), while six eyes (30%) suffered severe visual loss (six or more lines). The VA improved by five to six lines in three of 10 eyes with initial vision of 3/60 or worse. Three of four eyes receiving a second injection suffered either progressive cataract or elevated intra-ocular pressure (IOP) requiring cataract surgery and/or filtering surgery. One of 26 eyes (3%) receiving a single injection showed progression of cataract and elevation of IOP within 6 weeks of treatment and required anti-glaucoma medication for 6 weeks. Progression of nuclear sclerosis 8–12 months after treatment was observed in six of 26 eyes (23%) receiving a single injection. Conclusions: The results of the present study suggest that a single intravitreal injection of 4 mg triamcinolone is reasonably well tolerated by the human eye. The rate of development of severe visual loss was less than reported for historical controls. Because the results are preliminary and uncontrolled, the treatment should not be used routinely until its benefit to patients is established by a prospective, randomized controlled study.     

T1N0M0 bronchogenic carcinoma: assessment by CT

We reviewed medical records and conventional chest radiographs that showed a solitary T1N0M0 nodule in 23 patients who had non-oat-cell bronchogenic carcinoma. No patient had evidence of metastases, either on the chest radiograph or clinically. All patients underwent computed tomography (CT) examination of the thorax, including the adrenal glands. Only one patient (4%) had mediastinal lymph nodes greater than 1 cm in diameter accessible to mediastinotomy; anterior mediastinotomy confirmed metastatic spread in this patient, which precluded curative resection. Three patients each had a mildly enlarged (2 cm or less) adrenal gland; however, follow-up study suggested that metastasis was not the cause of adrenal enlargement in these patients. This study reinforces concern over whether CT is warranted in the preoperative assessment of T1N0M0 bronchogenic carcinoma.