Lipid hydroperoxides induce apoptosis in T cells displaying a HIV-associated glutathione peroxidase deficiency

8E5 is a chronically human immunodeficiency virus (HIV)-infected human T cell line, which we have previously shown to be extremely susceptible to hydrogen peroxide (H2O2)-induced apoptosis due to a HIV-associated catalase deficiency. Here we report that HIV gene expression additionally renders 8E5 cells 10-fold more sensitive than either uninfected A3.01 cells or HIV-infected but nonexpressing 8E5L cells to killing by 15-hydroperoxyeicosatetraenoic acid (15-HPETE), as well as several other hydroperoxy fatty acids. Whereas the viability of A3.01 and 8E5L cells was relatively unaffected by exposure to 10 microM 15-HPETE, similarly treated 8E5 cells underwent apoptosis, as demonstrated by morphological changes and the presence of fragmented DNA. The unique susceptibility of 8E5 cells was attributable to their inability to convert 15-HPETE to 15-hydroxy-eicosatetraenoic acid (15-HETE) owing to a marked reduction in glutathione peroxidase activity. Since oxidized lipids have been reported to accumulate in oxidatively stressed, HIV-infected individuals, a HIV-associated glutathione peroxidase deficiency may contribute to the depletion of CD4 T cells that occurs in the acquired immune deficiency syndrome (AIDS).     

Specific serological diagnosis of leprosy with a recombinant Mycobacterium leprae protein purified from a rapidly growing mycobacterial host

In this report we demonstrate the utility of an monoclonal antibody inhibition enzyme-linked immunosorbent assay based on the Mycobacterium leprae 35-kDa protein, purified from the rapidly growing host Mycobacterium smegmatis, for the serodiagnosis of multibacillary leprosy. The assay proved highly specific (97.5%) and sensitive (90%) and compared favorably with two other established methods routinely utilized for leprosy serodiagnosis.     

Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas

The goal of multimodality therapy for localized pancreatic cancer is to maximize local-regional disease control and patient survival. In contrast to surgery for other solid tumors, prolonged recovery following pancreaticoduodenectomy may prevent the timely delivery of postoperative adjuvant therapy. Therefore, efforts at The University of Texas, M.D. Anderson Cancer Center have focused on the delivery of chemotherapy and radiation therapy prior to surgery in patients with localized pancreatic cancer. Clinical trials have emphasized the use of altered-fractionation schedules of radiation therapy combined with novel radiation-sensitizing agents. All treatment schemes aim to decrease toxicity and treatment time while improving therapeutic efficacy.     

A novel helix termination mutation in keratin 10 in annular epidermolytic ichthyosis, a variant of bullous congenital ichthyosiform erythroderma

Annular epidermolytic ichthyosis is a distinct phenotypic variant of bullous congenital ichthyosiform erythroderma that has recently been described in two separate kindreds. Individuals with this variant present with bullous ichthyosis in early childhood and hyperkeratotic lichenified plaques in the flexural areas and extensor surfaces at later ages. Characteristically, they also develop intermittent bouts of annular and polycyclic, erythematous, scaly plaques on the trunk and proximal extremities. We now describe a third kindred with annular epidermolytic ichthyosis. Molecular analysis of this family revealed a novel mutation resulting in an isoleucine to threonine substitution at residue 107 (codon 446) within the highly conserved helix termination motif at the end of the rod domain of keratin 10.     

Continuous purification of porcine lipase by rotating annular size-exclusion chromatography

Non-accidental head injury, be it shaking, impact(s) or a combination of the two, is characterised by subdural and/or subarachnoid haemorrhages with retinal haemorrhages, but minimal or absent external cranio-facial trauma. The classical assault scenario depicts the infant being gripped around the head, face, chest and abdomen and shaken or being gripped by a limb and swung. This gripping might be expected to leave physical evidence in the form of bruising. A study was undertaken to establish the prevalence, distribution and pathological association of external bruising in 24 cases of fatal non-accidental head injury in children. At autopsy, 17 cases had new external bruises, 15 old external bruises and 13, a combination of both. However, seven (29%) cases showed no fresh external bruising and five (21%) showed no external bruising at all. Thus, external bruising may be absent in children with fatal intracranial injury. The face was shown to be the commonest site of bruising followed by the forehead and buttocks. Limb, chest and abdominal bruising were found to be uncommon. Retinal haemorrhages were confirmed in 23 (96%) cases. It is hypothesised that bruising, when present, may be a result of abuse in the form of punches and slaps rather than due to gripping during the assault. We discuss why gripping does not necessarily result in external bruising.     

Treatment of an isolated outer table frontal sinus fracture using endoscopic reduction and fixation

A case of an isolated frontal sinus fracture, reduced, fixed with miniplates and screws, and using the endoscopic technique, was presented. This case demonstrates the safety, efficacy, and economy of the endoscopic technique in properly selected cases that do not involve posterior table fractures or injury to the nasofrontal duct. The technique avoids the use of general anesthesia and the potential morbidities of coronal flaps.     

Alpha-2 adrenoceptor subtype causing nitric oxide-mediated vascular relaxation in rats

The alpha-2 adrenoceptor subtype and its signal transduction pathway mediating vascular relaxation in rats were studied in vitro using rings of superior mesenteric arteries. Removal of endothelium or incubation with NG-nitro-L-arginine completely blocked relaxant responses to UK14,304, suggesting endothelium-derived nitric oxide mediates relaxation. The order of potency for full (F) or partial (P) agonists causing relaxation was guanabenz (P) > UK14,304 (F) > clonidine (P) > epinephrine (F) > norepinephrine (F). Affinities (Ka) of alpha-2 adrenoceptor subtype-selective drugs for blocking relaxation were obtained in side-by-side experiments comparing rat mesenteric arteries with pig coronary arteries. Relaxation of pig coronary arteries is known to be mediated by the alpha-2A adrenoceptor subtype. Ka values in nM for rauwolscine (19), WB-4101 (265), SKF-104078 (197), spiroxatrine (128), and prazosin (1531) for blocking relaxation in rat arteries were consistent with their affinities for binding at the alpha-2D adrenoceptor subtype. Ka values for rauwolscine and WB-4101, drugs distinguishing the alpha-2D from the alpha-2A adrenoceptor subtype, were significantly higher in blocking relaxation of rat arteries compared with pig arteries, suggesting the alpha-2D adrenoceptor subtype mediates NO-induced relaxation in rat arteries. We used forskolin to oppose alpha-2 adrenoceptor-mediated inhibition of cAMP formation by directly stimulating cAMP formation in endothelium. Forskolin did not affect the relaxant response to UK14,304, suggesting that cAMP is not involved in the coupling of alpha-2 adrenoceptors to nitric oxide-induced vascular relaxation.