The hyperglycosylation of HIV envelope: An opportunity to alter virus infectivity?

Summary Glycosylation represents 50% of the molecular mass of the human immunodeficiency virus mature envelope glycoproteins (Env). The functional significance of this unusually high level of glycosylation has been partially clarified through a variety of experimental approaches and this has resulted in a demonstrable role for glycans in posttranslational events, including efficient intracellular routing and the functional folding of the molecule. Alteration of Env glycosylation may, therefore, modulate biological activity and offers the possibility of reducing virus pathogenicity; indeed, removal of glycosylation sites or alteration of the pattern of glycosylation by drug treatment have both been shown to lead to impaired virus infectivity. As a target for antiviral therapy based on the alteration of glycosylation, therefore, HIV Env represents an attractive target.     

Two novel cases of cerebral haemorrhages at the neonatal period associated with inherited factor VII deficiency, one of them revealing a new nonsense mutation (Ser52Stop).

Factor VII (FVII) is a plasma glycoprotein that plays a key role in the initiation of blood coagulation cascade. Inherited FVII deficiency is a rare autosomal recessive disorder with a wide heterogeneous clinical pattern. The severe form may be associated with intracranial haemorrhages occurring closely to birth with a high mortality rate. In the present article, we report two novel cases of neonatal intracerebral bleeding associated with FVII activity levels below 1% of normal. FVII genotyping investigations revealed particular genotypes including the deleterious Cys135Arg mutation and a novel Ser52Stop nonsense mutation at the homozygous state. Both mutations, through different mechanisms, are expected to be inconsistent with the production of functional FVII. These putative mechanisms are discussed through a review of the literature on phenotypic and genotypic characteristics of cerebral haemorrhages in severe inherited FVII deficiency.     

Clinical B12 deficiency in one case of recurrent spontaneous pregnancy loss.

Moderate hyperhomocysteinaemia (HHcy) and the homozygous mutation C677T in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene are associated with increased risk of recurrent pregnancy loss. This HHcy is currently reported as a consequence of folate rather than of vitamin B12-deficient status. We describe one case of recurrent early pregnancy loss with HHcy caused by B12 deficiency. A 38-year old woman had four episodes of early spontaneous pregnancy loss. Biological data: no haemostasis disorders, HHcy (25.9 micromol/l), normal folate (5 ng/ml), B12 deficiency (< 150 pg/ml) and the MTHFR C677T homozygote genotype. A bone marrow biopsy gave evidence of moderate megaloblastosis. Parenteral B12 therapy led to normal homocysteine level within 2 months and to a successful pregnancy. In conclusion, vitamin B12 deficiency is one of the causes of recurrent pregnancy loss associated with HHcy, and serum B12 should be measured systematically in this circumstance.     

Guidelines on the management of stable angina pectoris.

We read with great interest the recently published guidelineson the management of     

Associations between renal function, volume status and endotoxaemia in chronic kidney disease patients.

Inflammation is an important predictor of increased cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD), but the mechanisms behind the chronic activation of the immune system are not clearly understood. CKD patients develop fluid overload, which has been proposed to be a stimulus for inflammatory activation due to the translocation of macromolecules from the gut. We hypothesize that fluid overload is associated with signs of systemic inflammation and endotoxaemia in stages 1-5 CKD patients. The aim of this prospective study was to evaluate the associations between renal function, fluid status [evaluated by the inferior vena cava diameter (IVCD) and the collapsibility index (CI)], systemic inflammation [plasma levels of C-reactive protein (CRP), fibrinogen and albumin] and endotoxaemia (through the Limulus amebocyte lysate enzymatic assay) in a group of CKD patients in our out-patient clinic. The population consisted of 74 (mean of 57; range 23-83 years of age; 47% males) CKD patients with glomerular filtration rate (based on the mean of urea and creatinine clearances) of 34 ml/min. Both albumin (Rho = 0.25; P = 0.05) and fibrinogen (Rho= - 0.48; P < 0.0001) were significantly correlated to glomerular filtration rate (GFR). According to the IVCD, 84% of the patients were fluid overloaded, while 83% were considered overloaded by the CI. Signs of endotoxaemia were detected in all patients. Endotoxin levels were higher in patients with signs of fluid overload (0.85 +/- 0.11ng/l) when compared with patients with normal values of IVCD (0.61 +/- 0.05 ng/l; P < 0.05). Endotoxin levels correlated to both IVCD (Rho=0.33, P < 0.005) and CI (Rho = -0.25, P < 0.05). There was no correlation between endotoxin levels and GFR, CRP or fibrinogen. In summary, although most CKD patients presented signs of fluid overload that was associated with endotoxaemia, there was no association between endotoxaemia and systemic inflammation, suggesting the endotoxaemia may not be the main determinant of the inflammatory status in this group of patients.     

The pattern of metabolism of 2-acetylaminofluorene in carcinogen-induced hepatocyte nodules in comparison to normal liver

This study was designed to test further the hypothesis thatthe special biochemical pattern seen in hepatocyte nodules duringliver carcinogenesis could be of fundamental importance in theirselective metabolism of one carcinogenic xenobiotk, 2-AAF, asrelated to their resistance to xenobiotics. Nodules of a certainstage were induced using the resistant hepatocyte model. Themetabolism of a single small dose of 2-AAF in hepatocyte nodulesin comparison to normal liver was studied at different timeintervals up to 30 h. The levels of free 2-AAF in nodules andin normal liver were approximately the same over the whole timeperiod. However, the nodules showed a large decrease in thebinding of 2-AAF to DNA, RNA and proteins as well as in themetabolic conversion to hydroxylated forms, both free and conjugatedwith glucuronic acid. The patterns of metabolic conversion tometabolites and of conjugation of the metabolites are in harmonywith the known biochemical patterns in nodules, a decrease inphase I components involved in the metabolism of carcinogensand other xenobiotics and an increase in most phase II componentsinvolved in conjugation and detoxification.     

Source monitoring deficits in hallucinating compared to non-hallucinating patients with schizophrenia.

In two source memory tests, hallucinating patients with schizophrenia (N=30), compared to non-hallucinating (N=31), are impaired in recognizing internal self-generated items and misattribute them to an external event. They are not impaired in recognizing events from two internal sources. Results support a selective source-monitoring deficit in the occurrence of auditory hallucinations.     

Bariatric Surgery and Multiple Personality Disorder: Complexities and Nuances of Care

Background: Multiple personality disorder (MPD) can occur in patients with morbid obesity in need of bariatric surgery, though few reports noting this association exist in the literature. Herein we address MPD in morbid obesity, in the context of a patient presenting to us seeking surgical treatment of her morbid obesity. Methods: A 31-year-old morbidly obese (BMI 49 kg/m²) Hispanic female presented in early 1994 requesting bariatric surgery. She had been a victim of violent sexual abuse as a young girl. Subsequently, she developed at least three personalities, including one male personality. Results: Although she has lost nearly 45 kg after gastroplasty, her care has been complicated by her named multiple personalities. While MPD are infrequent and unfamiliar to most care providers, successful outcomes can be promoted with a proper approach. Conclusions: This patient's care illustrates that: (1) all personalities must agree to proposed operative intervention; (2) consent must be obtained from the ‘true’ patient; and (3) postoperative care and follow-up must address all personalities for an optimal outcome.