Humanization of high affinity anti-HBs antibody by using human consensus sequence and modification of selected minimal positional template and packing residues

We had earlier reported the construction and characterization of a high affinity recombinant scFv generated from a potential neutralizing mouse monoclonal antibody against the Hepatitis B surface antigen. In this report we describe the humanization of this scFv by grafting its antigen binding site onto framework of the human consensus sequence of highest similarity. We have used molecular modeling to alter not only the clearly permissible residues but also several minimal positional template and V_H/V_L interface residues. The humanized scFv retains the binding characteristic of the mouse monoclonal even under conditions that usually destabilize antigen antibody interactions. This high affinity humanized scFv provides a basis for the development of prophylactic/therapeutic molecules.     

Cytokeratins in primary cutaneous amyloidosis

The expression of keratins was investigated immunohistochemically on formalin-fixed and snap-frozen primary cutaneous amyloidosis tissue with a panel of monospecific and polyspecific antikeratin antibodies which recognized keratins K1, K5, K6, K7, K8, K10, K14, K16, K17, K18, and K19. Amyloid deposits in frozen section of seven cases of macular amyloidosis and lichen amyloidosus always reacted with antibodies LP34 (labeling K5, K6 and K18) MNF (labeling K5, K6, K8, K10, K17 and K18) and RCK 102 (labeling K5 and K8); frozen section in one case each of the seven cases also reacted with antibodies LL001 (labeling K14), Lp1K (labeling K7 and K17), and LP2K (labeling K19), LP1K (labelling K7 and K17), and LP2K (labelling K19), In formalin fixed section of 13 cases of macular amyloidosis and lichen amyloidosus amyloid deposits were labeled with LP34 in three section LL020 ()labelling keratins K5 and K6) in one section and LP2K in two section. In nodular primary cutaneous amyloidosis amyloid deposits were not labeled with any antikeratin antibodies. These data confirm that amyloid in macular amyloidosis and lichen amyloidosus contains keratin epitopes, and suggests derivation of the fibrillar component from keratin intermediate filaments Several different keratins appear to undergo conversion to amyloid, LP34, MNF 116 and RCK 102 antibodies, which have in common the labelling of keratin K5, may be useful in the diagnosis of macular and popular amyloidosis with frozen tissue section.     

What do all personality disorders have in common? Ineffectiveness and uncooperativeness

We still lack operative and theoretically founded definitions of what a personality disorder (PD) is, as well as empirically validated and feasible instruments to measure the disorder construct. The Temperament and Character Inventory (TCI) is the only personality instrument that explicitly distinguishes personality style and disordered functioning. Here, we seek to (1) confirm in a clinical sample that the character dimensions of the TCI capture a general construct of PD across all specific PD subtypes, (2) determine whether such core features can be used to detect the presence of PD, and (3) analyze whether such detection is affected by the presence and severity of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I symptoms. Two hundred five anxious/depressed outpatients were evaluated with the Structural Clinical Interview for DSM-IV Axis I and II Disorders. Assessment also included the TCI, the Hamilton rating scales for depression and anxiety, and the Panic and Agoraphobia Scale. Sixty-one patients (29.8%) were diagnosed as having a DSM-IV PD. Self-directedness and Cooperativeness, but no other TCI dimensions, predicted the presence of PD (Nagelkerke R(2) = 0.35-0.45) and had a moderate diagnostic utility (kappa = 0.47-0.58) when Axis I symptoms were absent or mild. However, accuracy decreased in anxious or depressed patients. Our study supports the hypothesis of a disorder construct that is not related to the intensity of any specific PD subtype but which is common to all PDs. This construct relies largely on internal representations of the self revealing ineffectiveness and uncooperativeness.     

Live/Real Time Three‐Dimensional Transthoracic Echocardiographic Assessment of Pericardial Disease

We studied 19 patients with pericardial disease using two‐dimensional and three‐dimensional transthorathic echocardiography (2DTTE and 3DTTE, respectively) in order to determine whether 3DTTE provides incremental value on top of 2DTTE in the evaluation of these patients. With 3DTTE a more comprehensive assessment of pericardial effusion can be made and both the parietal and visceral layers of the pericardium can be visualized en face and examined for pathologies and fibrin deposits. In our series of patients, 3DTTE was superior to 2DTTE in uncovering mass lesions involving the pericardium such as tuberculous granulomas and metastatic disease. Furthermore, it provided a better assessment of the nature of pericardial lesions, such as pericardial and mediastinal hematomas, pericardial cysts, and metastatic disease to the pericardium by sequential cropping of the 3D data sets and visualizing the interior of the lesions in a manner not possible with 2DTTE. It was also valuable in determining the extent of pericardial calcification in pericardial constriction and in measuring the size of pericardial masses. These preliminary results suggest the superiority of 3DTTE over 2DTTE in the evaluation of pericardial diseases and that it provides incremental knowledge to the echocardiographer. (ECHOCARDIOGRAPHY, Volume 26, November 2009)     

Anti-HIV, antimycobacterial and antimicrobial studies of newly synthesized 1,2,4-triazole clubbed benzothiazoles

In an attempt to synthesize pharmacologically active molecules, we report here the synthesis and in vitro anti-HIV, antimycobacterial and antimicrobial activity of various series of 3-(3-pyridyl)-5-(4-substitutedphenyl)-4-(N-substituted-1,3-benzothiazol-2-amino)-4H-1,2,4-triazole. The anti-HIV activity of the title compounds was evaluated as selective human immunodeficiency virus type-1 and -2 (HIV-1, HIV-2 RT) inhibitors, antitubercular activity against H₃₇Rv using Lowenstein-Jensen agar method and antimicrobial activity against certain bacterial and fungal strains using the broth microdilution method. The synthesized compounds were characterized by FTIR,¹H-NMR,¹³C-NMR and mass spectral data together with elemental analysis.     

A latent variable approach in simultaneous modeling of longitudinal and dropout data in schizophrenia trials

Dropouts impact clinical trial outcome analyses. Ignoring missing data is not an acceptable option when planning, conducting or interpreting the analysis of a clinical trial. Treatment related efficacy and safety data observed in the trial may not always be sufficient in explaining the dropouts' mechanism. Nevertheless, these dropout data may carry important treatment-related information and present as an outcome by itself. Traditional analyses involve the use of the time-to-event approach assuming that the dropouts' hazard is solely related to the efficacy or safety profiles observed in a study. A latent variable approach was developed to generalize this approach and to implement a more flexible dropout hazard function in a schizophrenia trial. This unobserved latent variable was used to jointly model the longitudinal efficacy data and dropout profiles across treatments. The analysis provides a framework to model informative dropouts simultaneously with primary efficacy outcomes and make intelligent decisions in drug development.     

Augmentation–Mastopexy Using an Autologous Parenchymal Sling

Background  

Mastopexy–augmentation is an important treatment to address breast deflation. Combining these two procedures is technique-sensitive, with a reported high revision rate and propensity for complications. We describe an approach to achieve aesthetic breast correction in an effective, reproducible, and safe manner while minimizing untoward sequela.     

Right Ventricular Dysfunction in Acute Myocardial Infarction Complicated by Cardiogenic Shock: A Hemodynamic Analysis of the Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) Trial and Registry

Background

The prevalence and significance of right ventricular dysfunction (RVD) in patients with cardiogenic shock due to acute myocardial infarction (AMI-CS) have not been well characterized. We hypothesized that RVD is common in AMI-CS and associated with worse clinical outcomes.