Identification of amino acid residues involved in dendrotoxin block of rat voltage-dependent potassium channels

alpha-Dendrotoxin (DTX) is a 60-amino acid peptide belonging to the family of mamba snake neurotoxins; it is a potent blocker of some but not all voltage-gated potassium currents. Potassium currents recorded from oocytes injected with cloned potassium channel RNAs also vary in sensitivity to DTX. Expression of channels that were chimeras of the DTX-sensitive channel RBK2 and the DTX-insensitive channel RGK5 showed that the putative extracellular loop between transmembrane domains S5 and S6 contributes strongly to DTX sensitivity. Mutation of two residues (Ala352Glu353) in this region of RBK1 to conform to those at equivalent positions in RGK5 (Pro374Ser375) reduced the potency of DTX about 70-fold, and the substitution of Tyr379 in RBK1 by its counterpart in RGK5 (His401) caused an additional 2.5-fold decrease in sensitivity. Converse substitutions in RGK5 significantly increased sensitivity to DTX. The results suggest that these residues contribute significantly to the channel-toxin interaction, providing further evidence that the S5-S6 loop lies at or near the external mouth of the channel, where DTX binding leads to channel occlusion. They offer a molecular explanation for the differences in DTX sensitivity observed among native potassium channels.     

Branhamella catarrhalis as a cause of pneumonia in a patient with miliary tuberculosis

Branhamella catarrhalis is increasingly reported as a cause of pneumonia in the immunocompromised host. The authors here report what they believe to be a unique case of B catarrhalis bronchopneumonia in a patient who had previously acquired miliary tuberculosis. The patient initially responded to medication but died suddenly following a brief episode of febrile illness. At autopsy, several lines of evidence implicated B catarrhalis in the findings. The authors review the literature regarding cases of lower respiratory tract infection reportedly caused by B catarrhalis. Their own conclusion is that B catarrhalis infection is not necessarily caused by abnormal immunoglobulin, as some workers have suggested, but rather by damaged lung tissue in general and damaged bronchoalveolar cells in particular.     

The contribution of risk factors to the effect of early otitis media with effusion on later language, reading, and spelling

A cohort of 946 children who were screened for otitis media with effusion (OME) from the ages of 2 to 4 were studied for language, reading, and spelling at 7 years of age. The effects of OME in combination with single risk factors and with increasing numbers of risk factors were investigated. An interaction with an additional risk factor was found only for gender and OME, with boys' spelling influenced negatively by a history of OME. OME in combination with preterm birth and low birthweight also appears to put children at risk for later langauage and educational problems. Although a negative linear relation between the number of risk factors and later functioning was found, it is suggested that OME, even when combined with a number of other risk factors, produces only minor effects on later language, reading, and spelling.     

The psychiatrist''s role in behavioral pediatrics training programs

Behavioral pediatric fellowships are available in 15 major medical institutions in the United States. In general, these programs focus on the psychologic, social, and biologic determinants of behavior and learning disabilities in children. Child psychiatry's participation in the formulative stages of these programs is considered vital. The authors caution psychiatry to avoid concentrating its energies upon these socially and developmentally inclined behavioral pediatricians to the detriment of all pediatric house staff.     

Fibroblast growth factor signaling in the developing neuroendocrine hypothalamus

Fibroblast growth factor (FGF) signaling is pivotal to the formation of numerous central regions. Increasing evidence suggests FGF signaling also directs the development of the neuroendocrine hypothalamus, a collection of neuroendocrine neurons originating primarily within the nose and the ventricular zone of the diencephalon. This review outlines evidence for a role of FGF signaling in the prenatal and postnatal development of several hypothalamic neuroendocrine systems. The emphasis is placed on the nasally derived gonadotropin-releasing hormone neurons, which depend on neurotrophic cues from FGF signaling throughout the neurons’ lifetime. Although less is known about neuroendocrine neurons derived from the diencephalon, recent studies suggest they also exhibit variable levels of dependence on FGF signaling. Overall, FGF signaling provides a broad spectrum of cues that ranges from genesis, cell survival/death, migration, morphological changes, to hormone synthesis in the neuroendocrine hypothalamus. Abnormal FGF signaling will deleteriously impact multiple hypothalamic neuroendocrine systems, resulting in the disruption of diverse physiological functions.