Coronary risk factor reduction through biofeedback-aided relaxation and meditation

The effects of behaviour modification through education and biofeedback-aided relaxation and meditation on the levels of blood pressure, pulse rate, smoking habits as well as serum cholesterol, triglycerides, and free fatty acids were studied in 18 normotensive, 18 smoking, and 22 hypertensive patients with 18 normotensive controls.

The results showed significant reduction in blood pressure, in all the treated groups; highly significant reduction in the number of cigarettes smoked by smokers; and reduction in some of the lipids in all the treated groups, but particularly in the hypertensive group. The therapy appears to be feasible and suitable for wider application. This approach is economical, acceptable to patients, and should be explored further.

     

Cellular content of amniotic fluid as predictor of central nervous system malformations.

Prospective observations on 442 consecutive samples have confirmed that pregnancies with CNS malformations are regularly associated with an abnormal cellular content of amniotic fluid. A crude semiquantitative test of the cell content can give valuable clinical information in relation to borderline amniotic fluid alpha-fetoprotein values, and help to detect false positive AFP's.     

Enhancement of cALL immunogenicity by co-culture with a CD154 expressing 293 cell line

Pre-B cell acute lymphoblastic leukaemia (cALL) commonly occurs in young patients and although successful conventional therapies are available (such as cytotoxic drugs and bone marrow transplantation) for a proportion of patients (approximately 30%) these are ultimately unsuccessful. Recurrence of disease is a result of the failure of the immune system to recognize these abnormal cells and down-regulation of crucial molecules required for cognate CD4(+) T cell recognition has been postulated as a means of immune escape. In this study we show that an embryonic kidney cell line (293 cells) transfected with CD154 (40 L.1) are capable of not only maintaining the viability of primary ALL cells in culture but can also up-regulate the expression of a number of crucial molecules involved in antigen recognition. We show that 40 L.1 cell stimulation of primary ALL cell cultures can not only enhance the allogeneic and autologous MLR response to such cells but will also induce CTL effectors which are capable of lysing wild-type autologous ALL cells. It is therefore conceivable that such an approach could be used to generate an active anti-tumour response in patients, following conventional therapy, reducing the incidence of recurrence.     

Effect of cetirizine on histamine- and leukotriene D4-induced bronchoconstriction in patients with atopic asthma.

Cetirizine, a derivative of hydroxyzine, is a new compound with potent antihistaminic property without antiserotonin and anticholinergic activities. The effect of both a single dose (15 mg) and 7 days of treatment (15 mg twice daily) with cetirizine, a potent H1 antagonist on bronchoconstriction induced by histamine and leukotriene D4 (LTD4) has been examined in 10 patients with mild atopic asthma in a placebo-controlled, double-blind, crossover study. Cetirizine, after a single dose and 7 days of treatment with placebo, the geometric mean values of the provocative concentration of histamine causing a 20% fall in FEV1 (millimolars) were 1.60 (95% confidence interval, 0.82 to 3.11) and 1.67 (0.77 to 3.65), compared with 118.07 (77.22 to 180.54) (p less than 0.0001) and 53.16 (20.50 to 137.84) after cetirizine administration (p less than 0.0002). The mean inhibition after a single dose was twofold higher than after 1 week of treatment (p less than 0.05). After a single dose and 7 days of treatment with placebo, the geometric mean values of the provocative concentration of LTD4 causing a 20% fall in FEV1 (micromolars) were 2.26 (1.74 to 2.94) and 2.37 (1.77 to 3.17), compared with 3.90 (2.60 to 5.86) (p less than 0.05) and 3.21 (2.28 to 4.52) after cetirizine administration. This result suggests that cetirizine is a potent H1 antagonist in the human airways. Diminished activity after 1 week of treatment suggests subsensitivity of H1 receptors developing in human airways. The small protective effect after a single dose against LTD4-induced bronchoconstriction indicates a nonspecific rather than a specific receptor antagonism.     

Gene deletions in spinal muscular atrophy.

Two candidate genes (NAIP and SMN) have recently been reported for childhood onset spinal muscular atrophy (SMA). Although affected subjects show deletions of these genes, these deletions can lead to either a very mild or a severe phenotype. We have analysed a large number of clinically well defined patients, carriers, and normal controls to assess the frequency and extent of deletions encompassing both of these genes. A genotype analysis indicates that more extensive deletions are seen in the severe form of SMA than in the milder forms. In addition, 1 center dot 9% of phenotypically normal carriers are deleted for the NAIP gene; no carriers were deleted for the SMN gene. Our data suggest that deletions in both of these genes, using the currently available assays, are associated with both a severe and very mild phenotype.     

Polyglutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2 chaperone

Spinal bulbar muscular atrophy is a neurodegenerative disorder caused by a polyglutamine expansion in the androgen receptor (AR). We show in transiently transfected HeLa cells that an AR containing 48 glutamines (ARQ48) accumulates in a hormone-dependent manner in both cytoplasmic and nuclear aggregates. Electron microscopy reveals both types of aggregates to have a similar ultrastructure. ARQ48 aggregates sequester mitochondria and steroid receptor coactivator 1 and stain positively for NEDD8, Hsp70, Hsp90 and HDJ-2/HSDJ. Co-expression of HDJ-2/HSDJ significantly represses aggregate formation. ARQ48 aggregates also label with antibodies recognizing the PA700 proteasome caps but not 20S core particles. These results suggest that ARQ48 accumulates due to protein misfolding and a breakdown in proteolytic processing. Furthermore, the homeostatic disturbances associated with aggregate formation may affect normal cell function.     

T cell subsets in idiopathic glomerulonephritis

Determination of T lymphocyte subsets using monoclonal antibodies revealed a deficiency of suppressor cells and an elevated helper:suppressor T cell ratio in 7 patients with untreated idiopathic immune complex glomerulonephritis and nephrotic syndrome. Possible pathogenetic mechanisms of immunoregulatory cell imbalance and their implications specifically in reference to idiopathic glomerulonephritis are discussed.     

Monoclonal antibodies to human secretory "pregnancy-associated endometrial alpha 1-globulin," an insulin-like growth factor binding protein: characterization and use in radioimmunoassay, Western blots, and immunohistochemistry

Monoclonal antibodies were raised against pregnancy-associated endometrial alpha 1-globulin (alpha 1-PEG), a 32 KD insulin-like growth factor binding protein (IGF-BP), which represents a major secretory product of the human decidualized endometrium during pregnancy. This class of IGF-BP has been implicated in the modulation of action, inhibitory and stimulatory, of insulin-like growth factors. Immunization with the protein purified from pregnancy endometrium resulted after myeloma fusion in the isolation of six hybridoma clones and the antibodies produced were characterized. The Ka of the antibodies ranged between 4.75 x 10(9) M-1 and 0.7 x 10(8) M-1. In Western blots all monoclonal antibodies reacted with purified protein of molecular weight 32 KD and specifically detected this IGF-BP species in culture medium and cytosolic extracts of pregnancy endometrium and amniotic fluid. The monoclonal antibodies appear to define three epitope-bearing regions as evidenced by their reactivity to polypeptide fragments of the protein. After synthesis and secretion by tissue explants in vitro the protein is susceptible to cleavage into fragments possessing different monoclonal antibody-defined reactivity. Employing immunohistochemical techniques the protein was principally localized to decidual cells in tissue sections of pregnancy endometrium and solely to these cells after enzymic digestion of the tissue. The implications of these results are discussed with respect to potential role of IGF-BP in the action of IGF upon the IGF-1 receptor-bearing populations, including lymphocytes and trophoblast cells, D in the decidua.     

On the ultrastructural diversity and essence of residual bodies in neuronal ceroid-lipofuscinosis.

In 4 patients with neuronal ceroid-lipofuscinoses (NCL) (3 patients with the junvenile type, 1 patient with the late infantile type), the ultrastructural spectrum of residual bodies in the central and peripheral nervous system presented curvilinear profiles in all cases and regions investigated and many more ultrastructural patterns within and beyond regions commonly accessible to biopsy, probably due to age dependence, local tissue and cellular biochemical factors. Sampling from basal ganglia especially yielded combined curvilinear-fingerpint bodies, from peripheral ganglia additional membranous bodies. Residual bodies in NCL were present in almost every cell type, similar to the distribution of regular lipofuscin. Although the classical subgroups of NCL contain electronmicroscopically well defined residual bodies, permitting distinction of the late infantile type from the juvenile type, the ultrastructural differences are more of a quantitative than of a qualitative nature. However, they are not pathognomonic. N.m.r. spectra of ceroid and lipofuscin support the concept of their biochemical similarity, and argue against the proposition that they contain a single major component.