Comparison of the ototoxic effect of kanamycin on albino and pigmented rats, studied using an operant method.

A study was made of the effect of daily administration of kanamycin (400 mg kg-1) on the hearing of Wistar albino and Lister hooded (pigmented) rats, which had been conditioned to discriminate an acoustic signal. In all animals except one, the drug caused severe, permanent hearing impairment and there was no difference between albino and pigmented rats in onset or degree. Other work has suggested a mediatory role for melanin pigment in such drug ototoxicity but the significance of this must be questioned in view of the failure to find any differences in functional deficit.     

具有三个CM公共值的亚纯函数的唯一性

本文指出仪洪勋和Brosch G在具有三个判别的CM公共值的亚纯函数的唯一性定理中,关于对数函数的导数是整函数的推导,可以用指数函数求导的方法来证明.改进了仪洪勋和Brosch G关于重值与唯一性定理.     

Comparison of the ototoxic effect of kanamycin on albino and pigmented rats,studied using an operant method

Summary A study was made of the effect of daily administration of kanamycin (400 mg kg^–1) on the hearing of Wistar albino and Lister hooded (pigmented) rats, which had been conditioned to discriminate an acoustic signal. In all animals except one, the drug caused severe, permanent hearing impairment and there was no difference between albino and pigmented rats in onset or degree. Other work has suggested a mediatory role for melanin pigment in such drug ototoxicity but the significance of this must be questioned in view of the failure to find any differences in functional deficit.This work was supported by a Fellowship toE. S. Harpur from the Department of Health and Social Services (Northern Ireland).     

Pain relief by xenograft of subarachnoid microencapsulated bovine chromaffin cells in cancer patients

The bovine chromaffin cells (BCC) implanted into the subarachnoid space can release analgesic substances such as opioid peptides and ealeeholamines. Clinical trials have provided the evidence that the implantation of polyvinylchloride ( PVC) hollow fiber encapsulated BCC by surgery can relief the pain in cancer patients. In the present study, BCC were encapsulated in alginate-polylysine-alginate (APA) mieroencapsules which protect the grafting of xenogeneic cells from host immune system anil allow BCC to function effectively without using immunosuppression agents. The microencapsulated BCCs (5 X 106~—8 X 106) were transplanted into the subarachnoid space I^._s of 17 patients who suffered from chronic cancer pain and had to have long-term administration of analgesics. The pain scores and morphine intake tesl showed that microencapsulated BCC graft totally stopped the chronic pain in three of the patients over a period of 200 days and in the other three over a period of 100 days. The resulls suggesl thai APA microencapsulated BCC xenotransplantation could be a novel alternative approach to managing pain of cancer patients.     

Killer cell immunoglobulin-like receptor 3DL1-mediated recognition of human leukocyte antigen B

Members of the killer cell immunoglobulin-like receptor (KIR) family, a large group of polymorphic receptors expressed on natural killer (NK) cells, recognize particular peptide-laden human leukocyte antigen (pHLA) class I molecules and have a pivotal role in innate immune responses. Allelic variation and extensive polymorphism within the three-domain KIR family (KIR3D, domains D0-D1-D2) affects pHLA binding specificity and is linked to the control of viral replication and the treatment outcome of certain haematological malignancies. Here we describe the structure of a human KIR3DL1 receptor bound to HLA-B*5701 complexed with a self-peptide. KIR3DL1 clamped around the carboxy-terminal end of the HLA-B*5701 antigen-binding cleft, resulting in two discontinuous footprints on the pHLA. First, the D0 domain, a distinguishing feature of the KIR3D family, extended towards β2-microglobulin and abutted a region of the HLA molecule with limited polymorphism, thereby acting as an 'innate HLA sensor' domain. Second, whereas the D2-HLA-B*5701 interface exhibited a high degree of complementarity, the D1-pHLA-B*5701 contacts were suboptimal and accommodated a degree of sequence variation both within the peptide and the polymorphic region of the HLA molecule. Although the two-domain KIR (KIR2D) and KIR3DL1 docked similarly onto HLA-C and HLA-B respectively, the corresponding D1-mediated interactions differed markedly, thereby providing insight into the specificity of KIR3DL1 for discrete HLA-A and HLA-B allotypes. Collectively, in association with extensive mutagenesis studies at the KIR3DL1-pHLA-B*5701 interface, we provide a framework for understanding the intricate interplay between peptide variability, KIR3D and HLA polymorphism in determining the specificity requirements of this essential innate interaction that is conserved across primate species.     

The influence of pigmentation of rats and guinea-pigs on the ototoxicity of kanamycin and neomycin.

Following the finding that melanin pigment played a role in the accumulation of ototoxic drugs in the inner ear, an investigation was made of the possible influence of the pigmentation of animals on their susceptibility to the ototoxic effects of drugs. Hearing acuity was assessed by measurement of acoustic startle reaction. Preliminary experiments suggested that pigmented animals might be more likely to suffer hearing impairment following ototoxic drug administration. However, in a controlled study using rats treated with kanamycin, it was not possible to confirm this and albino animals appeared no less vulnerable than pigmented animals to kanamycin-induced deafness.