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Biomedical subjects

G Murdoch

Publications and source records attributed to G Murdoch.

12 recordsLinked to original sources

Molecular characterization of a protein-tyrosine-phosphatase enriched in striatum.

A cDNA clone encoding a neural-specific putative protein-tyrosine-phosphatase (protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48) has been isolated from a rat striatal cDNA library. The deduced amino acid sequence predicts a protein of approximately 369 amino acids with a strong homology to other members of the family of protein-tyrosine-phosphatases. In vitro translation produces a protein with an apparent molecular mass of 46 kDa. A potential attachment mechanism to the cytoplasmic membrane is suggested by a myristoylation amino acid-consensus sequence at the N terminus of the protein. RNA analyses of various regions of rat brain reveal a 3-kilobase (kb) and a 4.4-kb mRNA. The 3-kb mRNA is highly enriched within the striatum relative to other brain areas and has been termed a "striatum enriched phosphatase" (STEP). In contrast, the 4.4-kb message is most abundant in the cerebral cortex and rare in the striatum. These two messages appear to be alternatively processed RNA transcripts of a single gene.

Amino Acid Sequence

Potential involvement of retroviral elements in human dementias.

Creutzfeldt-Jakob disease (CJD) is a dementia of humans caused by a class of infectious agents with several biological properties similar to those of conventional viruses. The molecular nature of this group of agents is enigmatic, for neither an agent-specific nucleic acid nor a non-host protein has yet been identified. Recent transmissions of familial CJD dementias to rodents suggest that this class of agent can be integrated into the germline. Furthermore, tissue culture studies indicate that CJD causes transformation of cells in a manner reminiscent of slowly oncogenic retroviruses. Currently characterized retroviral-like elements include many forms that do not have 'typical' retroviral ultrastructural morphology; several forms are also known to be resistant to various types of standard physicochemical inactivation. We suggest that CJD agents are either constituted by retroviral-like nucleic acids or interact with endogenous retroviral sequences to elicit a slowly progressive disease of the central nervous system. Several overlapping properties between infectious CJD and 'non-infectious' dementias, such as Alzheimer's disease, implicate potential common pathogenic mechanisms.

Alzheimer Disease

Further experience in the healing rate of lower limb amputations.

Results of lower limb amputation in the Tayside Region in the years 1981-1985 have been analysed. Three-hundred and twenty-four amputations were performed on three-hundred and eight patients. Two-hundred and thirty-six amputations were attempted at the below-knee level. Only 19 required proximal revision. Prior to amputation, all patients should have a detailed vascular assessment, and the operation should be performed by experienced amputation surgeons using meticulous technique.

Adult

Growth factor production by Creutzfeldt-Jakob disease cell lines.

Creutzfeldt-Jakob disease (CJD), a progressive dementia of humans, is caused by an infectious agent that is closely related to the scrapie agent of sheep. Although the molecular nature of these "unconventional" agents is still a matter of speculation and controversy, even less is known concerning the mechanism(s) of their effects on the central nervous system. To gain insight into the cellular effects of these agents, we have examined a series of cell lines derived directly from CJD-infected hamster brain or produced from nontransformed rodent lines by exposure to CJD infectious fractions in vitro. These cell lines appear transformed by a variety of criteria and secrete growth factors into the culture medium. All CJD lines produce a factor that is like alpha-transforming growth factor (alpha-TGF). Conditioned medium from these CJD lines also stimulates the synthesis of glial fibrillary acidic protein in normal astrocytic cells in vitro. This effect is mimicked by purified alpha-TGF and platelet-derived growth factors. Further study of CJD-induced growth factor production may elucidate fundamental properties of these unconventional agents.

Animals

Fate of the vascular patient after below-knee amputation.

50 below-knee amputations were carried out in 45 patients (25 men and 20 women), mean (SD) age 73 (10.5) years. The mean survival time was 22(16) months after the operation. In each patient the healing potential of a below-knee amputation was determined preoperatively by segmental pressure studies and thermographic delineation of skin perfusion. 33 of the stumps healed by first intention, in 14 healing was delayed but occurred without the need for further surgery, and 3 stumps healed after local wedge excision. The initial mobilisation rate was 90%. Thus, there are no grounds for carrying out an initial above-knee amputation to save the patient a further operation.

Aged

Decrease in human quadriceps muscle protein turnover consequent upon leg immobilization.

Quadriceps muscle protein turnover was assessed in the post-absorptive state in six men immediately after the end of unilateral leg immobilization (37 +/- 4 days) in a plaster cast after tibial fracture. A primed-constant intravenous infusion of L-[1-13C]leucine was administered over 7 h. Quadriceps needle biopsies, taken bilaterally at the end of the infusion, were analysed for muscle protein leucine enrichment with 13C. Quadriceps muscle protein synthetic rate, calculated from the fractional incorporation of [13C]leucine into protein compared with the average enrichment of blood alpha-ketoisocaproate, was 0.046 +/- 0.012%/h in the uninjured leg, but was only 0.034 +/- 0.007%/h in the quadriceps of the previously fractured leg (P less than 0.05, means +/- SD). Muscle RNA activity (i.e. protein synthetic rate per RNA) fell from 0.27 +/- 0.08 microgram of protein synthesized h-1 microgram-1 of RNA in the control leg to 0.14 +/- 0.03 microgram of protein synthesized h-1 microgram-1 of RNA in the immobilized leg (P less than 0.02). Immobilization was associated with a significant atrophy of type I muscle fibres (mean diameter 69.5 +/- 21 microns immobilized, 81.1 +/- 18 microns control, P less than 0.05), but no significant change occurred in type II fibre diameter. Mean quadriceps fibre volume calculated from the values for fibre diameter and percentage of each fibre type, was smaller in the injured leg by 10.6%; this value was near to the calculated difference in muscle thigh volume (calculated from thigh circumference and skin-fold thickness) which was less by 8.3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The pharmacokinetics of R- and S-tocainide in patients with acute ventricular arrhythmias.

The pharmacokinetics of R(-) and S(+)- tocainide were studied in twelve patients requiring intravenous tocainide. In all patients, a progressive increase in the S(+):R(-) ratio was observed during the infusion. Mean +/- s.d. ratios increased from 1.03 +/- 0.05 at 2 min to 1.76 +/- 0.35 at 48.5 h. Data from eight patients were fitted to a two-compartment model and there was a significant difference (Wilcoxon matched-pairs test P less than 0.01) in the clearance estimates for the two enantiomers. The median values were: S(+)-tocainide = 6.25 l h-1 and R(-)-tocainide = 9.31 l h-1. There was no differences in V1 or Vss.

Acute Disease