Biological activity of monoclonal antibodies to operationally defined antigenic regions on the hemagglutinin molecule of A/Seal/Massachusetts/1 /80 (H7N7) influenza virus

Monoclonal antibodies to the hemagglutinin (HA) molecule of A/Seal/Mass/1/80 (H7N7) have been prepared and used to establish an operational antigenic map. Four nonoverlapping antigenic areas on the HA of seal influenza viruses were defined. Monoclonal antibodies belonging to two of the groups (III and IV) failed to inhibit hemagglutination of intact virus yet effectively neutralized viral infectivity. These findings could not be explained by differences in affinities and were interpreted in terms of functional differences between the assays. Antibodies that failed to inhibit hemagglutination may bind nearer to the hydrophobic end of the HA molecule and might not block the receptor binding site for erythrocytes. Antibodies to these areas may inhibit infectivity by interference with cell fusion or viral replication. The monoclonal antibodies that failed to inhibit hemagglutination of intact virus nevertheless did inhibit HA activity of purified isolated rosettes of hemagglutinin. The mechanism of inhibition is not resolved but may involve the access of a larger number of antibody molecules to the HA when it is in the form of rosettes compared to when it is located on the viral membrane. The reactivity of seal influenza virus and other H7 viruses from birds with the monoclonal antibodies show that some avian strains possess HA molecules that are closely related to those of seal virus and may therefore be related to viruses that were important in the evolution of this strain. Since HI tests do not necessarily detect all antibodies that neutralize viral infectivity, the question is raised as to whether HI assays alone can be used for determining the efficacy of all influenza virus vaccines.     

B lymphocyte subset patterns and their significance in idiopathic glomerulonephritis.

The proportion of B lymphocyte subsets with surface immunoglobulin G (sIgG) was significantly increased in minimal change nephrotic syndrome (MCNS), membranous nephropathy, IgA nephropathy and mesangiocapillary glomerulonephritis (MCGN) and with sIgA in IgA nephropathy and MCGN, and with sIgE in MCNS. Increased subsets in membranous nephropathy, IgA nephropathy and MCGN corresponded to the immunoglobulins deposited in the glomeruli, and the increased subset of sIgE in MCNS was correlated with the elevation of serum IgE. These results suggest that each disease studied has a characteristic subset pattern of B lymphocyte response. This may have an important role in determining the histological type of idiopathic glomerulonephritis.     

Change in sonographic brightness can predict pathological response of triple-negative breast cancer to neoadjuvant chemotherapy

Introduction

Ultrasound (US) is conventionally performed to determine effects of neoadjuvant chemotherapy (NAC) on breast cancer. In patients with triple-negative breast cancer (TNBC), higher pathological complete response (pCR) predicts the most favorable survival outcome. We aimed to predict pCR to NAC using echogenicity changes in US region of interest (ROI) in patients with TNBC.

Methods and materials

We retrospectively determined clinicopathological characteristics of 52 patients with primary TNBC who underwent NAC. Changes in echogenicity for pCR and non-pCR patients were calculated from ratios of tumor to fat (T/F) in their ROIs, before and after NAC, as [T/F _After/T/F _Before] and [T/F _After ? T/F _Before].

Results

Of the 52 patients (median age: 52 years; range 26–77 years), 20 (38.5%) achieved pCR, which was significantly associated with change in ROI ratio (P < 0.01). The cut-off values for ROI ratio and ROI difference were 0.8 and 0.3. Sensitivity and specificity were 73.7 and 81.8% for ROI ratio, and 70.0 and 81.3% for ROI difference. Area under the curves (AUCs) for ROI ratio and ROI difference were 0.80 [95% confidence interval (CI) 0.67–0.92] and 0.78 (95% CI 0.64–0.92), respectively.

Conclusion

Quantification of echogenic changes by converting absolute values of tumor and fat regions can predict pCR and individual differences between tumors after NAC in patients with TNBC.

     

The role of monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein (MCP)-1 in subgroups of rapidly progressive glomerulonephritis

To elucidate the role of monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein(MCP)-1 in the pathogenesis of rapidly progressive glomerulonephritis (RPGN), we determined the urinary levels of MCAF/MCP-1 in 20 healthy subjects, 30 patients showing RPGN with crescents, and 39 patients with various types of renal diseases without crescents. We divided RPGN into two subgroups, the acute type and the insidious type, with regard to the declination rate of reciprocals of serum creatinine with time as previously reported. In addition, we divided the patients with RPGN into anti-neutrophil cytoplasmic antibody(ANCA)-related diseases and immune complex(IC)-mediated diseases with regard to etiology. Urinary levels of MCAF/MCP-1 were significantly higher in patients with RPGN as compared with those of other renal diseases and healthy volunteers(21.8 +/- 4.5 vs. 11.6 +/- 3.5, 1.0 +/- 0.1 pg/ml creatinine, respectively, p < 0.01, mean +/- SEM). There was no difference in the urinary levels of MCAF/MCP-1 between the acute and insidious types of RPGN patients. In addition, there was no difference in the urinary levels of MCAF/MCP-1 between the patients with ANCA-related and IC-mediated diseases. Urinary levels of MCAF/MCP-1 in patients with RPGN were correlated well with the percentage of both total crescents and fibrocellular/fibrous crescents and the number of CD68-positive infiltrating cells in the interstitium. Immunohistochemical examinations revealed that MCAF/MCP-1 positive cells were detected in tubular epithelial and endothelial cells and mononuclear infiltrated cells in the interstitium. Moreover, elevated urinary MCAF/MCP-1 levels in patients with RPGN, regardless of subgroups, were dramatically decreased during methylprednisolone pulse therapy induced convalescence. These results suggest that MCAF/MCP-1 may be involved in the pathogenesis of RPGN via macrophage recruitment and activation.     

Increased urinary excretion of pyridinoline and deoxypyridinoline in a girl with congenital contractural arachnodactyly

Congenital contractural arachnodactyly (CCA) is caused by mutations in the gene for fibrillin 2 glycoprotein, a component of connective tissue. The causes of osteodystrophy or osteodysplasia in CCA are unknown. We report bone metabolism in a 28 month-old girl with CCA. Serum alkaline phosphatase and osteocalcin levels were 650 IU/l and 22 ng/ml at 1.5 months old (control: 530+/-65, 16.5+/-4.3), and 580 IU/l and 21 ng/ml at 28 months old (control: 465+/-58, 15.0+/-3.5), i.e. in upper-normal levels. The urinary pyridinoline and deoxypyridinoline levels were 1176 and 194 micromol/mol creatinine at 1.5 months old (control: 329+/-76, 63+/-12), and 407 and 111 micromol/mol cr at 28 months old (control: 231+/-49, 50+/-11), apparently higher than the control values. These findings may indicate that abnormal fibrillin may impair bone metabolism and cause the osteodystrophy or osteodysplasia in CCA.     

The ramification of the superficial branch of the superior gluteal artery. Anatomical basis of a new gluteus maximus myocutaneous flap

Summary In order to design a new gluteus maximus myocutaneous flap, the ramification of the superficial branch of the superior gluteal artery was investigated in 56 sides of 33 Japanese cadavers. The superficial branch constantly divides into two main branches, which are called the ascending and transverse branches in this study. Of the ascending and transverse branches, one or both usually give off at least one well developed division running on the undersurface of the gluteus maximus muscle (98.2%). This division, which is called the intermediate branch in this study, generally reaches the superior edge of the muscle giving off only a couple of muscular branches and pierces the muscle and its deep fascia to supply skin (83.6%). Perforators of the intermediate branch constantly emerge from the fascia near the middle or lower one-third point on a line extending from the middle of the iliac crest to the tip of the greater trochanter.

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Les ramifications de la branche superficielle de l'artère gluteale supérieure. Bases anatomiques d'un nouveau lambeau myocutane de muscle grand fessier

Résumé Dans le but de créer un nouveau lambeau myocutané de muscle grand fessier, les ramifications de la branche superficielle de l'artère glutéale supérieure ont été étudiées chez 33 sujets japonais (56 cotés). La branche superficielle se divise de façon constante en deux rameaux principaux, qui seront appelés dans cette étude les branches ascendante et transverse. De l'une de ces deux branches, ou parfois des deux, naît souvent au moins un rameau bien développé courant sous le muscle grand fessier (98,2%). Cette branche de division, qui est nommée dans cette étude le rameau intermédiaire, atteint généralement la limite supérieure du muscle, en abandonnant seulement quelques rameaux musculaires, et perfore le muscle et son fascia profond pour vasculariser la peau (83,6%). Les branches perforantes du rameau intermédiaire traversent le fascia, de façon constante, au niveau du milieu ou du tiers inférieur d'une ligne tendue du milieu de la crête iliaque au sommet du grand trochanter.

     

Anti-rat CD45RA monoclonal antibodies cross-react with glucagon

Anti-rat CD45RA monoclonal antibody (MAb) has been used as a marker for rat B-lymphocytes (B-cells). When we applied the MAb to identify B-lymphocytes among immune cells infiltrating pancreatic islets of the BB rat, which is an animal model for human type 1 diabetes mellitus, a subpopulation of islet cells was immunostained as well. Our immunohistochemical investigations demonstrated that the stained islet cells are pancreatic alpha-cells and the MAb cross-reacts with glucagon.     

Pathways of Fluid Drainage from the Brain - Morphological Aspects and Immunological Significance in Rat and Man

There is firm physiological evidence for the lymphatic drainage of interstitial fluid and cerebrospinal fluid from the brains of rats, rabbits and cats. The object of this review, is to describe firstly the morphological aspects of lymphatic drainage pathways from the rat brain and secondly, to explore through scanning and transmission electron microscope techniques, the possibility of similar lymphatic drainage pathways in man. Interstitial and oedema fluid spreads diffusely through the white matter in the rat and appears to drain into the ventricular cerebrospinal fluid. In grey matter, however, tracers pass along perivascular spaces to the surface of the brain and into the cerebrospinal fluid. Paravascular compartments in the subarachnoid space follow the course of major arterial branches to the circle of Willis and thence along the ethmoidal arteries to the cribriform plate of the ethmoid bone. Particulate tracers, such as Indian ink, enter channels in the arachnoid beneath the olfactory bulbs and connect directly with nasal lymphatics through channels which pass through holes in the cribriform plate. Proteins and other solutes may also drain along other cranial nerves. Thus, there is a bulk flow pathway for interstitial and cerebrospinal fluid from the rat brain into cervical lymphatics. In man, it is probable that diffuse interstitial drainage of fluid from the white matter occurs in a similar way to that in the rat. Furthermore, the anatomical pathways exist by which bulk drainage of fluid could occur along perivascular spaces from the grey matter into perivascular spaces of the leptomeningeal arteries and thence into the cerebrospinal fluid (CSF).(ABSTRACT TRUNCATED AT 250 WORDS)