137 research outputs found
Synaptic Transmission from Horizontal Cells to Cones Is Impaired by Loss of Connexin Hemichannels
In the vertebrate retina, horizontal cells generate the inhibitory surround of bipolar cells, an essential step in contrast enhancement. For the last decades, the mechanism involved in this inhibitory synaptic pathway has been a major controversy in retinal research. One hypothesis suggests that connexin hemichannels mediate this negative feedback signal; another suggests that feedback is mediated by protons. Mutant zebrafish were generated that lack connexin 55.5 hemichannels in horizontal cells. Whole cell voltage clamp recordings were made from isolated horizontal cells and cones in flat mount retinas. Light-induced feedback from horizontal cells to cones was reduced in mutants. A reduction of feedback was also found when horizontal cells were pharmacologically hyperpolarized but was absent when they were pharmacologically depolarized. Hemichannel currents in isolated horizontal cells showed a similar behavior. The hyperpolarization-induced hemichannel current was strongly reduced in the mutants while the depolarization-induced hemichannel current was not. Intracellular recordings were made from horizontal cells. Consistent with impaired feedback in the mutant, spectral opponent responses in horizontal cells were diminished in these animals. A behavioral assay revealed a lower contrast-sensitivity, illustrating the role of the horizontal cell to cone feedback pathway in contrast enhancement. Model simulations showed that the observed modifications of feedback can be accounted for by an ephaptic mechanism. A model for feedback, in which the number of connexin hemichannels is reduced to about 40%, fully predicts the specific asymmetric modification of feedback. To our knowledge, this is the first successful genetic interference in the feedback pathway from horizontal cells to cones. It provides direct evidence for an unconventional role of connexin hemichannels in the inhibitory synapse between horizontal cells and cones. This is an important step in resolving a long-standing debate about the unusual form of (ephaptic) synaptic transmission between horizontal cells and cones in the vertebrate retina
Work-related allergy in medical doctors: atopy, exposure to domestic animals, eczema induced by common chemicals and membership of the surgical profession as potential risk factors
Purpose To investigate the risk factors associated with
work-related allergy-like symptoms in medical doctors.
Methods Self-administered questionnaire survey and CAP
test were conducted among medical school students in the
4th grade of their 6-year medical course in 1993–1996 and
1999–2001. Follow-up questionnaires were sent in 2004 to
the graduates. These questionnaires enquired into personal
and family history of allergic diseases, lifestyle, history of
allergy-like symptoms including work-relatedness and
occupational history as medical doctors. Relationships
between allergy-like symptoms and relevant factors were
evaluated by multivariate logistic regression analysis.
Results Of 261 respondents at the follow-up survey, 139
(53.3%) and 54 (20.7%) had a history of any allergy-like
symptoms and any work-related allergy-like symptoms,
respectively. Female gender and family history of allergic
diseases were signiWcantly associated with any allergy-like
symptoms. Personal history of allergic disease, exposure
to domestic animals, eczema caused by rubber gloves,
metallic accessories, or cosmetics during schooling days,
and membership of the surgical profession were signiW-
cant risk factors for work-related allergy-like symptoms.
On the contrary, to work-related allergy-like symptoms,
gender, age, and smoking status were not signiWcantly
related, and consumption of prepared foods was inversely
related.
Conclusions Personal history of atopy and eczema
induced by common goods and the history of keeping
domestic animals may be predictors of work-related
allergy-like symptoms in doctors. After graduation from
medical school, physicians start with exposure to various
allergens and irritants at work, which relate to work-related
allergy-like symptoms, especially for surgeons
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