Biomedical subjects

K A West

Publications and source records attributed to K A West.

At least 37 records · Page 2Linked to original sources

PubMed1995

Functional effects of a natural polymorphism in the transcriptional regulatory sequence of HLA-DQB1.

DNA sequence polymorphism in the genes encoding HLA class II proteins accounts for allelic diversity in antigen recognition and presentation and, thus, in the role of these cell surface glycoproteins as determinants of the scope of the T-cell repertoire. In addition, sequence polymorphism in the promoter-proximal transcriptional regulatory regions of these genes has been described, particularly for the HLA-DQB1 locus, where these differences may contribute to variation in locus- and allele-specific expression. In this study, we measured the effect of such regulatory sequence polymorphism on the expression of endogenous alleles of DQB1 in heterozygous cells. Quantitative reverse transcriptase-mediated PCR analysis showed that expression of the DQB1*0301 allele responded more rapidly to gamma interferon induction than that of DQB1*0302. We have analyzed functional effects of a prominent allelic polymorphism that consists of a TG dinucleotide present between the W and X1 consensus elements in the DQB1*0302 allele but missing in the DQB1*0301 allele. The dominant effect of this polymorphism was to introduce a variation in the spacing between the W and X1 elements of these two alleles. A secondary compensatory effect was specific for the TG dinucleotide itself, which was essential for the binding of a nuclear protein complex to the *0302 regulatory region immediately 5' of the X1 element. Derivatives of the DQB1 5' regulatory region were used to drive expression of the chloramphenicol acetyltransferase gene in transient transfections of human B-lymphoblastoid and gamma interferon-treated melanoma cell lines, demonstrating that the additional spacing between the W and X1 elements caused by the presence of the TG dinucleotide in the *0302 allele resulted in reduced expression compared with that driven by the *0301 fragment; this difference overshadowed an up-regulating effect on expression which corresponded to the binding of the TG-dependent nuclear protein complex. The presence of this polymorphism in multiple HLA-DQB1 alleles and in several species suggests selection for two alternative transcriptional regulatory mechanisms influencing expression of alleles of the same HLA locus.

Alleles↗

PubMed1993

Mitochondrial HSP60 (P1 protein) and a HSP70-like protein (mortalin) are major targets for modification during S-(1,1,2,2-tetrafluoroethyl)-L-cysteine-induced nephrotoxicity.

The potent and site-selective nephrotoxicity of S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC) in vivo has been associated with difluorothioamidyl-L-lysine formation on critical mitochondrial target proteins. Dose-response studies in the Fischer 344 rat indicate that five proteins with apparent molecular masses of 99, 84, 66, 52, and 48 kDa are predominantly adducted in vivo after nephrotoxic doses of TFEC (> 10 mg/kg, intraperitoneally). Microsequence analysis of the major difluorothioamidyl-L-lysine proteins indicated that P66 is identical, over 14 NH2-terminal residues, to mitochondrial P1 protein (HSP60, a chaperonin) and that P84 is identical, over 14 residues, to a recently isolated novel member of the HSP70 family known as mortalin. These studies indicate that mitochondrial heat shock proteins are major targets for modification by reactive metabolites of TFEC. The implications of these data in relation to the nephrotoxicity of cysteine conjugates are discussed.

Amino Acid Sequence↗

PubMed1989

Human epidermal growth factor (EGF) receptor sequence recognized by EGF competitive monoclonal antibodies. Evidence for the localization of the EGF-binding site.

Epitopes recognized by three epidermal growth factor (EGF) competitive monoclonal antibodies, LA22, LA58, and LA90, have been localized to a 14-amino acid region in the extracellular domain of the human EGF receptor. The binding of each of these mutually competitive antibodies to A431 epidermoid carcinoma cells was inhibited up to 87% by EGF. Furthermore, binding to A431 cells was inhibited 100% by the EGF competitive monoclonal antibody 528 IgG. The EGF receptor monoclonal antibody 455 IgG, which recognizes a blood group A-related carbohydrate modification of A431 receptors and does not inhibit EGF binding, did not inhibit the binding of these three antibodies to A431 cells. Antibodies LA22, LA58, and LA90 were unusual in that they bound to recognized denatured and endoglycosidase F-treated antigenic determinants in Western blots. This suggested that the antibodies recognized continuous peptide epitopes. The epitopes for these antibodies were first localized in cyanogen bromide- and V8 protease-generated fragments of a truncated form of the EGF receptor secreted by A431 cells. In experiments with synthetic peptides, all three antibodies were found to bind to the 14 amino acids from Ala-351 to Asp-364 of the mature human EGF receptor. These amino acids are located between the two Cys-rich regions of the extracellular domain of the receptor, and they include an Arg-Gly-Asp-Ser recognition site for adhesion molecule receptors. The homologous sequence in the chicken EGF receptor, which binds mouse EGF with a 100-fold lower affinity than the human EGF receptor, contains four amino acid differences including two in the Arg-Gly-Asp-Ser tetramer. The mutually competitive binding of EGF and antibodies LA22, LA58, and LA90 implied that the amino acids between Ala-351 and Asp-364 participated in the formation of the EGF-binding site of the human EGF receptor.

Amino Acid Sequence↗

PubMed1984

Retrospective analysis of 162 consecutive cases of ruptured intracranial aneurysms. Total mortality and early surgery.

A retrospective analysis of 162 consecutive cases with ruptured intracranial aneurysm treated during the years 1979-1981 is presented. Total mortality was 33%. Eighty-four patients were in Botterell grades I-II and 62 were operated with a direct attack on the aneurysm. Thirty-eight were operated early with a mortality of 5% compared with 13% for those operated late. There was no difference in morbidity between the two groups. Of the patients operated with clipping, 66% made a "complete recovery" and 21% were classified as independent. Signs of delayed ischaemia were recorded in 42% of patients operated early as compared with 25% in the late surgery group. The frequency of rebleedings in the total material was 15%. Hospitalization time was significantly reduced in the early operated group. The importance of analysing the total management mortality and morbidity for evaluation and comparison between early and delayed surgery is discussed.

Adult↗

PubMed1984

Clinical experience with the use of a temporary clip for intracranial aneurysm surgery. Analysis of eighteen cases.

Although the use of a temporary clip in intracranial aneurysm surgery has been proposed by several Neurosurgeons in the past, its use today is not generally accepted. Modern surgical techniques have contributed to safer exposure and direct attack on the aneurysm. However, aneurysm surgery continues to be a direct attack on the aneurysm. However, aneurysm surgery continues to be a challenge to the Surgeon and occasionally demands the use of a temporary clip. Eighteen cases operated on with the use of a temporary clip have been analysed. The occlusion time of the feeding vessel and location of the temporary clip have been related to the outcome. There was no relationship between occlusion time of the feeding vessel and outcome in this material, whereas location of the temporary clip seemed to be of importance for the outcome in cases with aneurysms located in the middle cerebral artery.

Adult↗

PubMed1982

Treatment of chronic obsessive compulsive states with stereotactic anterior capsulotomy or cingulotomy.

A neuropsychological model on how to evaluate patients subjected to stereotactic psychosurgery is presented. Four patients with chronic obsessive compulsive neurosis were randomly assigned to either stereotactic anterior capsulotomy or cingulotomy, and assessed pre-, peri-, and postoperatively according to this model. The best immediate and long-term follow-up results in reducing obsessional symptoms were obtained in the two capsulotomized patients. Psychosurgery should only be performed by a multidisciplinary team of specialists, with objective evaluation, adequate information on patients, and reliable test instruments.

Adult↗

PubMed1978

Cerebral aneurysm in an infant with fibromuscular hyperplasia of the renal arteries. Case report.

The authors report a case of subarachnoid hemorrhage in an 11-month-old infant with tragic outcome. Radiological investigation showed an anterior communicating aneurysm, and postmortem examination confirmed the aneurysm to be a so-called "berry" aneurysm. There were also typical signs of fibromuscular hyperplasia of the renal arteries. The microscopic findings are discussed. In view of the rarity of both aneurysms and fibromuscular hyperplasia in such a small child, a possible association of these entities suggested by several earlier investigators is reviewed.

Arterial Occlusive Diseases↗

PubMed1976

Effect of sympathetic denervation on chronic cold injuries in rabbit brain. A microangiographical and histological study.

Sympathetic denervation of the brain vessels was performed uni- or bilaterally in 13 adult rabbits, and cortical cold lesions were induced bilaterally 10-18 days afterwards. After a further 4-35 days the vascular and morphological changes in the lesion areas were studied histologically and with angiography. No difference was observed between the denervated and the non-denervated lesion areas. The results are discussed with regard to a proposed functional plasticity of the chronically denervated brain vessels and/or to possible changes in metabolic demands of the brain tissue.

Angiography↗

PubMed1975