Mitochondrial tRNALeu isoforms in lung carcinoma cybrid cells containing the np 3243 mtDNA mutation

We have investigated the representation of structural isoforms of the two mitochondrial leucyl tRNAs in lung carcinoma cybrid cell lines containing the np 3243 (MELAS) mtDNA mutation, alone or in combination with the np 12300 suppressor mutation. The mutant tRNALeu(UUR) is aminoacylated very poorly or not at all, whereas the suppressor tRNALeu(CUN) is efficiently aminoacylated. Deacylated mitochondrial tRNALeu(CUN) is present, in all human cells tested, in two structural isoforms that are separable on denaturing gels, indicating a difference in primary structure. The ratio of the two isoforms differs between cell types and is strongly biased towards one isoform in lung carcinoma cybrids containing high levels of the np 3243 mutation, compared with control cybrids. We propose that structural modification of tRNALeu(CUN) could be a natural suppression mechanism for the np 3243 and other mitochondrial tRNALeu(UUR) mutations and could underlie some of the phenotypic variability of np 3243 disease.      

ANGIOTENSIN II- AND PHORBOL ESTER-INDUCED STEROIDOGENESIS BY OVINE ADRENOCORTICAL CELLS: EFFECT OF SEX AND THE GONADAL STATUS OF THE DONOR ANIMAL

1. Angiotensin II (Angll) is well recognized as a regulator of adrenal Cortisol production in the sheep in vivo, but studies to date have failed to reveal this action on cultured ovine adrenocortical cells. Similarly, phorbol myristate acetate (PMA), an activator of protein kinase C, also has little effect on Cortisol production from ovine adrenocortical cells in vitro. Previous studies have, however, only looked at the responses to single concentrations of Angll or PMA, but have led to the suggestion that important differences exist between adrenocortical cells of the sheep and other species. 2. We have extended previous studies by examining Cortisol production by ovine adrenocortical cells over 3h in response to a broad range of concentrations of either Angll (10^?10 to 10^?6mol/L) or PMA (10^?10 to 10^?5mol/L). In addition, we have investigated the possible role of gonadal factors in regulating these responses by comparing cultures derived from intact and gonadectomized male and female sheep. 3. Angiotensin II caused concentration-dependent increases (P<0.05) in Cortisol production in all cultures, with Cortisol production in response to Angll being greater (P < 0.05) in cultures from intact male sheep than in the cultures from orchid-ectomized males or intact females. Cortisol production in response to Angll was modest in all groups (two- to 2.6-fold increases). 4. Phorbol myristate acetate elicited a concentration-dependent inhibition (P<0.01) of basal Cortisol production in adrenocortical cultures from all groups. Phorbol myristate acetate produced a greater inhibition (P<0.05) of Cortisol production in cultures from intact male sheep than either the orchidectomized males or intact females. 5. These findings demonstrate that ovine adrenocortical cells are responsive in a concentration-dependent fashion to Angll and PMA. In addition, sex and gonadal factors may play an important role in regulating the responsiveness of adrenocortical cells to these factors.     

Tongue Metastasis from a Poorly Differentiated Urothelial Carcinoma of the Bladder

Chemotherapy may cause oral ulceration but a thorough investigation of symptoms and signs is important to determine the underlying diagnosis accurately. We describe a case of a patient with a poorly differentiated urothelial carcinoma of the bladder developing a tongue metastasis. This is a challenging diagnosis to make given the rarity of the presentation but it illustrates the need to evaluate any new symptoms fully.     

Progressive dysfunction of monocytes associated with iron overload and age in patients with thalassemia major

We evaluated phagocytic and lytic activities of peripheral blood monocytes (PBMo) from patients with thalassemia major (ThP) using C pseudotropicalis as the target. PBMo from ThP showed decreased lytic activity (P less than .001), whereas the phagocytic activity did not differ from that of the controls. Significant inverse correlations were found between lytic activity of PBMo and age of patients (r2 = .47; P less than .01) and also between lytic activity and serum ferritin levels (r2 = .65; P less than .001). No association was found between lytic activity and other variables (blood transfusion regimens, therapy with desferrioxamine, liver damage, and the presence of sHBAg). Splenectomy showed no positive effect on PBMo functions from ThP. Our results suggest that PBMo from ThP have an intracellular defect in their microbicidal mechanisms associated with iron overload. This cell dysfunction could be responsible, at least in part, for the increased susceptibility to infections reported in ThP.     

辐射增敏研究动向

目前在肿瘤的临床放射治疗中,如果采用正常组织可耐受的照射剂量进行治疗,肿瘤的平均治愈率仅40%,提高射线对肿瘤的杀伤率之关键,仍在于克服那些对射线敏感性较差的乏氧细胞。     

Factor X deficiency in the neonatal period

An infant with a severe deficiency of factor X presened in the neonatal period with uncontrollable bleeding from heel prick sites, spontaneous bruising, and haematoma. The deficiency was controlled by infusions of dried human factors II, IX, and X concentrate; the half-life of the infused factor X material is only 18 hours. Despite prophylactic weekly infusions of factor X concentrate, the child developed a fatal intracerebral haemorrhage when only 4 months old. Coagulation studies on both parents and the elder sister showed no obvious coagulation abnormality.     

WIDE ANGLE ATTACHMENT FOR FUNDUS CAMERAS

A simple and inexpensive method for increasing the angle of view of existing fundus cameras used for fluorescein angiography is described. The addition of a concavo-convex positive lens extends the usefulness of the camera and contributes to the efficiency of diagnosis.