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The Leu-8/TQ1 antigen, recently shown to be the human equivalent of the murine MEL-14 lymph node homing receptor and now designated as leucocyte-endothelial cell adhesion molecule, LECAM-l, has been used to dissect T, B and natural killer (NK) cells into various subpopulations with different functional properties, such as suppressor-inducer (CE4+ Leu-8/TQ1+) or helper (CD4+ Leu-8/TQ1-) T lymphocytes. Diminished Leu-8/TQ1 antigen density has been reported after lymphocyte activation with B- or T-cell specific stimuli for several days. In the present study, we sought to determine the signal requirements for altered Leu-8/TrQ1 expression. Exposure of freshly isolated peripheral blood lymphocytes to phorbol 12-myristate 13-acetate (PMA) and/or calcium ionophores was found to cause rapid down-regulation of the Leu-8 antigen, with little or no Leu-8 reactivity remaining I hr after simultaneous addition of PMA and calcium ionophores to the culture medium. TQ1 reactivity was changed in parallel with that of Leu-8. Leu-8 expression oft and B cells was sensitive to both PMA and calcium ionophores, whereas Leu-8 expression of NK cells was affected by PMA but not by the calcium ionophore A23187. The effect of PMA on Leu-8/TQ1 expression could be antagonized by pretreatment with the protein kinase C inhibitor, H7, whereas that of A23187 could not. Partial re-expression of the Leu-8 antigen was seen 3 days after addition of PMA alone but not when it was given together with calcium ionophores. After Leu-8 down regulation induced by I hr treatment with PMA or calcium ionophores, Leu-8 re-expression was observed within 24 hr when stimuli were removed by washing. Activation oft cells with anti-CD3 antibody resulted in a partial reduction of Leu-8/TQ1 expression, first detectable after 1-3 hr of stimulation and maximal at 24 hr. Fully mitogenmic concentrations of concanavalin A (Con A) did not affect Leu-8 expression within the first hours of culture. Transient reduction of Leu-8 expression was seen 24 hr after supraoptimal dosages of Con A, but Con A-stimulated lymphocytes cultured for 4-12 days with interleukin-2 (IL-2) retained Leu-8/TQ1 reactivity to a similar degree as fresh cells. In contrast to Leu-8/TQ1, CD45RA expression was not altered after I hr treatment with PMA and/or calcium ionophores but gradually disappeared during I week after Con A stimulation. Thus, Leu-8/ TQ1+ CD45RA+ lymphocytes could be rapidly converted into Leu-8/TQ1 CD45RA+ cells by PMA and/or calcium ionophores in vitro within 1 hr, whereas Leu-8/TQ1+ CD45RA- cells were generated by Con A stimulation over several days. [ABSTRACT FROM AUTHOR]

Cases are presented which show the clinical utility of recording an electrocochleographic response to bone-conducted stimuli. The procedure is fraught with problems of acoustic control and artifact generation, but has distinct although limited values in clarifying masking dilemmas in patients with bilateral hearing loss. [ABSTRACT FROM AUTHOR]

Our experience with an application and technique for electrocochleography, specifically in retardates, is reported. A case is presented in detail; that is, a mongoloid child with many overlapping otological and audiological diagnostic problems. With the combined use of cochleography and tympanometry much of this diagnostic confusion was resolved and management was simplified. This technique is also compared with late evoked cortical audiometry. [ABSTRACT FROM AUTHOR]

Directed migration of lymphocytes from blood into lymph nodes and gut-associated lymphatic tissue, also referred lo as homing, is subject to change following activation. Lymphocyte migration into lymphoid organs in vivo and binding to high endothelial venules in vitro is largely suppressed after short-term stimulation with phorbol esters. The observed functional alterations were correlated with changes in the expression of three putative homing receptors. LECAM-1 (MEL-14 antigen), LPAM-l/2 (α4-integrin) and the murine CD44 (Pgp-1, H-CAM, Hermesantigen equivalent) upon different modes of cellular activation. Expression of LECAM-I (gp90 MEL-14), a lymphocyte adhesion molecule implicated in targeting extravasation into lymph nodes, was found to be lost almost completely within minutes after protein kinase C activation. LECAM-1 re-expression occurred within less than 24 h. Rapid loss of LECAM-1 was also observed after calcium ionophores whereas anti-CD3 or concanavalin A elicited a gradual and heterogeneous loss of LECAM-1 becoming detectable after several hours only. A number of cytokines tested were not able to induce alterations in LECAM-1 expression. In contrast, expression of LPAM-1/2 (α-integrin) and CD44 (Pgp-1. H-CAM), two adhesion molecules supposed to direct extravasation into Peyer's patches, remained stable for hours after every stimulus tested; CD44 expression gradually increased 24 h after mitogenic activation, whereas a small reduction only was observed for the expression of the α4-chain under certain conditions. Thus, reduced extravasation of lymphocytes into Peyer's patches after activation is not due to a decline in the surface density of LPAM-1/2 α-chain or CD44 whereas alterations in migration into lymph nodes parallel the expression of LECAM-1. [ABSTRACT FROM AUTHOR]

Genetic and auditory studies of 731 children with severe-to-profound hearing loss in US schools for the deaf and 46 additional children receiving clinical services for hearing loss ranging from moderate to profound demonstrated that mutations in the connexin 26 (GJB2) and connexin 30 (GJB6) genes explain at least 12% of those with nonsyndromic sensorineural deafness. Otoacoustic emissions (OAEs) testing to detect functional outer hair cells indicated that 76 of the children had emissions and therefore may have (as yet unconfirmed) auditory neuropathy/dys-synchrony (AN/AD). Five of these children with OAEs were GJB2 homozygotes or compound heterozygotes with the genotypes 35delG/35delG, W77X/W77X, 35delG/360delGAG, 35delG/V95M, and V84M/M34T. In particular, unilateral AN/AD was confirmed in a child with moderate hearing loss and the 35delG/V95M genotype. Detecting OAEs in individuals with GJB2 mutations suggests that lack of functional gap junctions as a result of GJB2 mutations does not necessarily destroy all outer hair cell function.

Objective: To describe and compare women and health care professionals' preferences for Down's Syndrome screening tests with different test characteristics., Design: Cross sectional questionnaire based conjoint analysis study., Setting: London teaching hospital., Sample: 291/383 women in their first or second trimester of pregnancy and 98/122 health care professionals (41 obstetricians, senior house officers and above and 57 qualified midwives) providing care at the same hospital., Methods: Women completed a questionnaire while attending a clinic visit for a dating scan or a routine 20-week anomaly scan. Health care professionals completed a postal questionnaire., Main Outcome Measures: The relative values participants attach to Down's Syndrome screening test attributes: time of test, detection rate and risk of miscarriage of a baby unaffected by Down's Syndrome as a result of subsequent diagnostic tests., Results: Pregnant women and health care professionals shared broadly similar relative values regarding the importance of safe tests, conducted early and with high detection rates. When asked to choose between different Down's Syndrome screening tests, health care professionals valued earlier tests more highly than did women., Conclusions: While pregnant women and health care professionals share similar relative values regarding optimal prenatal tests, health care professionals place a higher value on earlier tests. This may result in screening policies that overweight timing in the selection of a test to the relative neglect of tests associated with lower miscarriage rates and higher detection rates but conducted later in pregnancy.