Differential contribution of the FcRγ chain to the surface expression of the T cell receptor among T cells localized in epithelia: analysis of FcRγ-deficient mice

The function of the Fc receptors γ chain (FcR_γ) for the expression of the T cell receptor (TCR) complex and for T cell development, especially for T cells localized in epithelia, was investigated by analyzing FcR_γ-deficient mice. In wildtype mice, CD8αα⁺β^?TCRαβ⁺ T cells of intestinal intraepithelial lymphocytes (i-IEL) utilized CD3ζ homodimers and ζ-FcR_γ heterodimers, whereas CD8α α⁺β^?TCR_γδ⁺ i-IEL used ζ-FcR_γ and FcR_γ homodimers in the TCR complex. On the other hand, these T cells in FcR_γ-deficient mice contained only ζ homodimers. The surface expression of the TCR complex was reduced in CD8αα⁺β^?i-IEL and dendritic epidermal T cells (DETC) in these mice, whereas the development of these T cells was normal. The degree of reduction appeared to depend on the expression level of FcR_γ. In contrast to these populations, TCR_γδ⁺ intraepithelial T cells in reproductive organs (r-IEL) were dramatically decreased, suggesting that the development of r-IEL is FcR_γ-dependent, probably due to the predominant usage of FcR_γ homodimers in the TCR complex. These results indicate that the FcR_γ chain contributes differently to the TCR expression and to the development of T cells localized in epithelia.     

Central atypical papillomas of the breast: a clinicopathological study of 119 cases

The clinicopathological features of central intraductal papillomas of the breast presenting with florid usual ductal hyperplasia or atypical ductal hyperplasia (ADH) were analyzed in a retrospective series of 119 patients, whose lesions were sent to the Armed Forces Institute of Pathology from 1976 to 1990. After histological review considering predefined morphological and quantitative criteria, the 119 central papillomas were classified into 22 papillomas with florid usual ductal hyperplasia (18%), 40 papillomas with focal atypia (34%), 24 atypical papillomas (20%) and 33 carcinomas arising in a papilloma (28%). After a median period of follow-up of 110 months, 16 recurrences (5 papillomas, 2 carcinomas arising in a papilloma, 4 ductal carcinomas in situ, 5 invasive carcinomas) occurred. No statistically significant difference was observed in relation to recurrence for the various categories of papillomas. The presence of epithelial hyperplasia, ADH or lobular neoplasia in the surrounding breast as well as infarction of the papilloma were significant predictive factors of recurrence (P=0.02 and P=0.005, respectively, log-rank test). The main reason for the observed low rate of significant recurrences in this series was that epithelial atypia (whether comprising 20% or 60% of the papillary lesion) was, in most of the cases, localized in a confined lesion that was completely excised.     

Morphological features of nerve terminal degeneration as part of the remodeling process in the motor endplate in adult muscles

With the exception of signs of retraction and withdrawal, there have been few morphological data concerning degenerated neural profiles in adult motor endplates. Here, investigation into the ultrastructure of the soleus motor endplates of adult rats (4 months old) turned up particular axonal degeneration in approximately 3% of the subjects. These axons occur as synaptic debris in the synaptic matrix of the motor endplate, adjacent to thin processes of the perisynaptic cells occupying the outer most layer of the motor endplate and were devoid of basal lamina. They often possessed dense-cored vesicles (50-80 nm). Axonal debris released from Schwann cell processes occurred during the period of acute sciatic neurectomy, when nerve terminals progressively disrupted within the motor endplate associated Schwann cells. Finally, immunohistochemical staining for antibodies to label macrophages (ED1 or ED2) has shown that nerve fiber-associated macrophages are located near the motor endplate. The results suggest that during the course of endplate remodeling, a few parts of the terminal branches are disposed of through spontaneous collapse, subsequent release from the Schwann cell investment, and eventual ingestion by macrophages in the perisynaptic space.     

2型糖尿病并血管病变患者免疫功能研究

目的 :探讨 2型糖尿病并血管病变患者血液中细胞免疫、体液免疫和C反应蛋白 (CRP)的变化。方法 :采用流式细胞术和免疫比浊法测定 42例糖尿病血管病变患者血液细胞免疫参数CD3、CD4、CD8、CD4/CD8、B细胞和NK细胞、血清免疫球蛋白 (IgG、IgA、IgM)、补体 (C3、C4)等体液免疫参数和作为炎症介质的CRP ,并与5 0例 2型糖尿病无血管病变者及 46例正常对照组比较。结果 :2型糖尿病无论是否并发血管病变 ,与正常对照组比较CD3、CD4、CD4/CD8、B、NK显著性减低 (P <0 .0 1) ,IgA、IgM、C3、C4、CRP显著升高(P <0 .0 1) ;并发血管病变组与不并发血管病变组比较C4、CRP显著增高 (P <0 .0 1)。结论 :2型糖尿病患者无论是否并发血管病变 ,机体细胞免疫和体液免疫都异常 ,且炎症介质CRP升高 ,并发血管病变患者机体的炎症介质进一步升高。     

Bronchiolar expression of aquaporin-3 (AQP3) in rat lung and its dynamics in pulmonary oedema

Aquaporins (AQPs) are water channel proteins that permit osmotically driven water movement. To determine their dynamics in pulmonary oedema, we examined the expression of mRNA and protein for AQP1, AQP3, AQP4, and AQP5 in the lungs of normal and thiourea-treated rats. In the thiourea group, lung water content increased significantly (vs. controls) with the peak at around 4 h. Semi-quantitative RT-PCR showed that AQP3 mRNA in the thiourea group rose significantly, peaking at around 4–8 h. The expression of AQP1, AQP4, AQP5, ENaC and CFTR mRNA each decreased significantly some time after the peak in lung water content. Immunoblot analysis showed that glycosylated AQP3 protein was increased 4–10 h after treatment. Expression of the other AQP proteins was not significantly altered, except for that of AQP4. Immunohistochemical examination revealed that AQP1 was expressed in endothelia, AQP3 in the basal cells of the large airways and in cuboidal cells in the bronchioles, AQP4 in the basolateral membrane of airway cells and AQP5 in type-I pneumocytes. Our results suggest that AQP3 is expressed not only in large airways, but also in bronchioles, and is related to water movement in pulmonary oedema.     

Sodium channels in ocular epithelia

Voltage-gated, tetrodotoxin(TTX)-blockable sodium channels are found in most excitable cells and are the primary contributors to action potentials generated by many of these cells. To date, there has only been one report of a non-cultured vertebrate epithelial cell type containing TTX-blockable Na⁺ channels: rabbit non-pigmented ciliary body epithelial cells [Cilluffo MC et al. (1991) Invest Opthalmol Vis Sci 32:1619–1629], and three reports of cultured epithelial cells containing TTX-blockable Na⁺ channels: rabbit non-pigmented and pigmented ciliary body epithelium [Ciluffo MC et al. (1991) Invest Opthalmol Vis Sci 32:1619–1629; Fain GL, Farahbakhsh (1989) J Physiol (Lond) 417:83–103] and human lens epithelium [Cooper K et al. (1990) J Membr Biol 117:285–298]. We report here the presence of sodium currents in two different non-cultured, freshly dissociated transporting epithelial cell types: the rabbit corneal endothelium and the frog lens epithelium. We also report the occurrence of sodium currents in six additional cultured ocular epithelial cell types from three different species. These currents have a current/voltage (I/V) relationship consistent with traditional voltage-gated Na⁺ currents, are quinidine- and TTX-blockable (of the low-affinity TTX-sensitive type), and disappear following bath substitution of Na⁺ with Cs⁺ or K⁺.     

Inhibition of sodium transport by angiotensin II in the main duct of the rabbit mandibular gland isolated and perfused in vitro

Summary The effect of angiotensin II on nett electrolyte transport by the main duct of the rabbit mandibular gland was investigated in vitro using a perfused duct preparation bathed in a Haemaccel^®-nutrient salt solution. In a bath concentration of 4×10^–10 M, angiotensin reduced nett absorption of Na⁺ and Cl^– by about 8% and depolarized the transepithelial electrical potential difference (P.D.) by about 13%; the drug had no effect on ductal transport of K⁺ and HCO ₃ ^– . In both lower (4×10^–11 M) and higher (4×10^–9 M) concentrations, angiotensin had qualitatively similar effects. After exposure to the hormone for about 30 min, Na⁺ transport and P.D. became unstable and gradually fell away towards zero. It is concluded that angiotensin in physiological concentrations has a specific inhibitory effect on Na⁺ absorption by salivary duct cells which could arise either from a change in the Na⁺ pump rate or from a conductance change in the apical or basal membrane of the epithelial cell.     

A Randomized Study of Epithelial Ovarian Cancer: Is Chemotherapy Useful after Complete Remission?

Objective. The aim of this study is to verify whether consolidation chemotherapy with Cisplatin improves disease-free survival and/or overall survival in patients affected by epithelial ovarian cancer.Methods. A multicenter study examined 122 randomized patients in complete remission as judged by laparoscopy or laparotomy following first-line chemotherapy consisting of ACy (Adriamycin + Cyclophosphamide), PCy (Cisplatin + Cyclophosphamide), or Mitoxantrone + Carboplatin. Sixty-one of these patients were treated with 3 cycles of 5-Fluorouracil (FU) 500 mg/m2 for 5 days followed by Cisplatin at 100 mg/m2 on the 6th or 7th day every 28 days; the other 61 received no further treatment (nihil group).Results. Sixty patients in the Cisplatin arm were evaluable. There were 36 relapses in the FU+Cisplatin arm and 30 in the nihil arm. Peritoneal relapses were 25% for Cisplatin treatment vs. 16.4 % for nihil. There were 29 deaths in the Cisplatin arm vs. 27 for nihil. Median overall survival time (95 months with Cisplatin vs. 96 months in the nihil group) and median disease-free survival (66 months with Cisplatin vs. 73 in the nihil group) were similar in both arms (p=0.66 and p=0.41, respectively). There were no significant differences in tumor stage and grade between the two arms. Seven patients presented a second neoplasm during follow-up: six in the nihil arm, but only one patient in the Cisplatin arm. Death in these patients was due to the second neoplasm and not to progression of ovarian cancer.Conclusion. Three courses of additional platinum+FU treatment after five cycles of first-line chemotherapy without FU produced no increase in overall survival or disease-free survival.     

Arsenic uptake,cytotoxicity and detoxification studied in mammalian cells in culture

The cytotoxicity of trivalent and pentavalent inorganic arsenic salts was determined in mouse fibroblasts in vitro. Concentrations of As (III) in the M range led to a reduction of proliferation and viability with a concomitant increase in LDH release and stimulation of lactic acid production. Similar effects were noted with approximately 10-fold greater molar concentrations of As(V). Cells pretreated with a low As(III) concentration are less sensitive to toxic doses of As(III) or As(V).Uptake of As(III) by the fibroblasts is greater than that of As(V). Both forms of inorganic arsenic are converted intracellularly to monomethylarsonic (MMA) and dimethylarsinic (DMA) acids, which are then released into the culture medium. In As-pretreated cells, which are more resistant to As toxicity, biotransformation of inorganic arsenic to MMA and DMA is increased.