Neutralizing antibodies from the sera of human immunodeficiency virus type 1-infected individuals bind to monomeric gp120 and oligomeric gp140

Antibodies that neutralize primary isolates of human immunodeficiency virus type 1 (HIV-1) appear during HIV-1 infection but are difficult to elicit by immunization with current vaccine products comprised of monomeric forms of HIV-1 envelope glycoprotein gp120. The limited neutralizing antibody response generated by gp120 vaccine products could be due to the absence or inaccessibility of the relevant epitopes. To determine whether neutralizing antibodies from HIV-1-infected patients bind to epitopes accessible on monomeric gp120 and/or oligomeric gp140 (ogp140), purified total immunoglobulin from the sera of two HIV-1-infected patients as well as pooled HIV immune globulin were selectively depleted of antibodies which bound to immobilized gp120 or ogp140. After passage of each immunoglobulin preparation through the respective columns, antibody titers against gp120 and ogp140 were specifically reduced at least 128-fold. The gp120- and gp140-depleted antibody fraction from each serum displayed reduced neutralization activity against three primary and two T-cell line-adapted (TCLA) HIV-1 isolates. Significant residual neutralizing activity, however, persisted in the depleted sera, indicating additional neutralizing antibody specificities. gp120- and ogp140-specific antibodies eluted from each column neutralized both primary and TCLA viruses. These data demonstrate the presence and accessibility of epitopes on both monomeric gp120 and ogp140 that are specific for antibodies that are capable of neutralizing primary isolates of HIV-1. Thus, the difficulties associated with eliciting neutralizing antibodies by using current monomeric gp120 subunit vaccines may be related less to improper protein structure and more to ineffective immunogen formulation and/or presentation.     

The evaluation of normal corneal topography in emmetropic eyes with computer-assisted videokeratography

Positron emission tomography (PET) has been widely used in the study of stroke and related cerebrovascular diseases. It has shown the various stages leading to cerebral infarction and defined the significance of the ischaemic penumbra. PET scan can predict the clinical outcome of patients with acute ischaemic stroke. Several types of diaschisis can also be demonstrated by PET. They reflect different pathophysiological changes in supratentorial infarcts. Post-apoplectic seizures are shown to increase the ischaemic damage in the affected cerebral hemisphere. PET has contributed also to the concept of multi-infarct dementia, although the significance of chronic ischaemia in the pathogenesis of vascular dementia has not been fully investigated.     

Influence of dosage form on the gastroenteropathy of flurbiprofen in the rat: evidence of shift in the toxicity site

PURPOSE: Gastroduodenal and intestinal permeability were compared after single doses of sustained release and regular release flurbiprofen in the rat to assess possible site-specific formulation-dependent toxicity. METHODS: Pharmacokinetics was assessed and gastrointestinal permeability was evaluated using sucrose and 51Cr-EDTA as gastroduodenal and intestinal permeability probes, respectively. RESULTS: The two formulations demonstrated equal areas under the flurbiprofen concentration-time curve. The sustained release formulation peaked 2-3 h slower with 57-74% lower concentrations than regular release formulation. In comparison, the regular release powder induced greater gastroduodenal permeability while sustained release granules induced greater intestinal permeability. When S-flurbiprofen concentrations were plotted versus intestinal permeability, a linear relationship and an anti-clockwise hysteresis were obtained for regular and sustained release formulations, respectively. CONCLUSIONS: Sustained release formulations of flurbiprofen demonstrate reduced gastroduodenal permeability but shift the site of this side-effect to the more distal intestine.     

The dexamethasone suppression test and treatment outcome in elderly depressed patients participating in a placebo-controlled multicenter trial involving moclobemide and nortriptyline

A 28-year-old woman was referred to us to undergo 131I therapy who had multiple pulmonary metastases from papillary thyroid carcinoma after total thyroidectomy. There was no increased accumulation of a tracer in the pulmonary metastatic foci on whole-body scanning using a 111 MBq diagnostic dose of 131I. However, the pulmonary metastases were gradually decreased in size, and then clearly reduced 8 months after the start of TSH suppression therapy, which was maintained by T3 instead of T4 to bring down the serum TSH level below 0.1 microU/ml. Reduction rates of the foci were 33-76% on chest X-ray. The reduction was confirmed and no new lesions were found on the serial CT scans. Serum thyroglobulin level was lowered 80 to 25 ng/ml by this suppression therapy and progression of disease was not observed under a 54 months' T3 treatment. Thus, TSH suppression therapy might improve survival of patients with differentiated thyroid cancer.     

Comparison of results and risk factors of cardiac surgery in two 3-year time periods in the 1990s

With the increasing number of treatment options for heart disease, decision-making requires profiles of risk for conventional cardiac surgery. Refinements in techniques and clinical practices seem to have reduced surgical risk. This study was performed to determine current risk factors. From July 1, 1990, to June 30, 1996, 1,036 consecutive patients underwent 1,042 heart operations using standard incisions and cardiopulmonary bypass with cardioplegia. Univariate and multivariate analyses using a logistic regression model were performed to determine factors significant for combined 30-day and hospital mortality. To determine if there were trends in the results and the risk factors, the last 500 consecutive cases in the series were analyzed separately. Overall, 30-day mortality was 17 of 1,042 (1.6%) and combined 30-day and hospital mortality was 27 of 1,042 (2.6%). Significant risk factors for combined 30-day and hospital mortality by multivariate analyses were: emergent/resuscitative status, preoperative dialysis, left ventricular ejection fraction < or = 30%, valve operation, and creatinine > or = 1.5 mg/dl. Comparison with baseline characteristics of the patients undergoing the last 500 consecutive operations to the earlier 542 operations in the study group showed that risk factors had a very similar profile for the 2 groups. The overall 30-day mortality for the last 500 consecutive operations was 5 of 500 (1.0%) and combined 30-day and hospital mortality was 8 of 500 (1.6%). The significant risk factors by multivariate analyses were reduced to left ventricular ejection fraction < or = 30% and creatinine > or = 1.5 mg/dl. These results indicate that modern techniques and clinical practices have mitigated well-recognized risk factors in conventional cardiac surgery and this trend is ongoing.