Biomedical subjects
Publications and source records attributed to A Smith.
We report a retarded male with an unbalanced karyotype 45,XY,t(8;15) (p23;q12) showing small deletion of chromosome 8(p23 leads to pter) and 15(pter leads to q12). The same chromosome complement was also present in 4 normal family members over 3 generations.
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The clinical features of testicular feminization in the racoon dog (Nyctereutes procyonoides) are reported. The condition is characterized by a normal male karyotype, but a mixed phenotype consisting of vulva, enlarged clitoris and scrotal testes. Partial spermatogenesis with a relative arrest at the first meiotic division was observed. The likely underlying genetic defect and mode of inheritance are discussed, together with implications for breeding programmes.
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Investigation of factors affecting the speed of diagnosis, referral and treatment of 113 patients with colorectal cancer shows that failure to examine the patient was significantly associated with delay. Patients who were not given a rectal or abdominal examination at their first medical consultation experienced considerably more delay in being referred for specialist opinion. Factors affecting the decision to examine are described.
The NH2-terminal blocking group of the Ca2+-binding B-subunit of calcineurin (protein phosphatase-2B) has been identified as myristic acid by fast atom bombardment mass spectrometry and gas chromatography. The sequence, myristyl-Gly-Asn-Glu-Ala-, is very similar to that of the catalytic subunit of cyclic AMP-dependent protein kinase, the only other protein known to contain this fatty acid. This finding, and the elution of all myristyl peptides at 57% acetonitrile on reverse phase HPLC, may facilitate the identification of other proteins with this blocking group.
A new method is described for the measurement of oxalate in urine and urinary calculi using medium pressure ion-chromatography. The technique is simple, requires minimal sample preparation and only 20 min analysis time. The minimum detection limit for oxalate is 0.5 mumol/l in the diluted sample as applied to the analyser. The intra-run coefficient of variation for the chromatography stage alone is 3.8%. The overall intra-run and inter-run coefficients of variation, including the sampling and dilution of urine, are 6.5 and 8.3% respectively. The method compares well with an established colorimetric technique for the analysis of oxalate both in urine and in urinary calculi.
Single motor unit activity was recorded from human lower lip muscles while subjects maintained a firing rate of 20 ips using audio and visual feedback. Each motor unit was classified as belonging to one of three muscles, orbicularis oris inferior (OOI), mentalis (MENT), or depressor labii inferior (DLI). Reflex responses were elicited in single motor units by applying small mechanical displacements (0.5 mm) to the corner of the mouth. Reflex responses were analyzed by constructing peristimulus histograms. Of 130 units analyzed, 123 showed statistically significant changes in their probability of firing in the 50 ms period following the stimulus. Reflex responses were typically polymodal with both excitatory and suppression components present. The excitatory responses occurred at latencies consistent with previous descriptions of the perioral reflexes and were labelled E1 (means = 15.9 ms) and E2 (means = 35.6 ms). Reflex suppression responses (S) were also consistently observed. There was a tendency for the pattern and/or relative magnitudes of reflex response components to depend on the muscle classification of the motor unit; E1 responses predominating in OOI units, E2 responses in MENT units, and S responses in DLI units. This finding provides preliminary evidence for muscle-specific projections between the trigeminal sensory system and facial nucleus motoneurones in humans.
Anti-mouse lymphocyte globulin and normal immunoglobulin have been conjugated to abrin using two procedures, one involving linkage through an amide bond and a piperazine ring and the other the introduction of two amide bonds flanking a disulphide bridge. The four conjugates produced were equipotent as inhibitors of protein synthesis in rabbit reticulocyte lysates. Each antibody-containing conjugate was a more effective inhibitor of protein synthesis in cultured cells than the equivalent normal immunoglobulin-containing conjugate. In addition the conjugates with disulphide linkage groups were ten times more potent than their counterparts. The disulphide conjugates were also twice as toxic to mice in an acute toxicity test but when used to suppress their immune responses to sheep red blood cells it was the non-disulphide-linked conjugates that were superior. In all instances antibody-containing conjugates were more powerful immunosuppressants than those containing normal IgG. The results are taken to indicate a relative lack of stability of the disulphide conjugates in the tissues.
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Clinical features were noted and routine and non-routine laboratory variables were measured before elective major gastrointestinal surgery in 63 patients aged 40 years or more. Deep-vein thrombosis (DVT), detected by routine 125I-fibrinogen leg scanning, developed in 21 patients. Five clinical variables but no laboratory variables were significantly associated with DVT: age; percent mean weight for age, sex, and height (%MW); presence of varicose veins; cigarette-smoking; and sex. The most useful discriminant index of these variables was age in years plus 1.3 x %MW. The index was validated prospectively in a further 41 patients, in 18 of whom DVT developed. The value of the index in selective prophylaxis was then assessed in a further 40 patients, of whom 24 (60%) with high-risk index received low-dose heparin (5000 units twice daily). DVT developed in 4 of the 40 patients, an incidence of 10% compared with the incidence of 37.5% (39 of 104) in the earlier studies with no prophylaxis.
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Data relating to 1022 patients with early breast cancer who were entered into a clinical trial have been analysed to assess the importance of various factors in predicting prognosis. Clinical stage was the major determinant of prognosis, and in each stage patients with a breast tumour 2 cm or less in maximum diameter had a significantly better survival than patients with larger tumours. Patients aged between 40 and 49 years and premenopausal patients had relatively favourable prognosis. Site of the tumour within the breast, whether it was situated on the left or the right side, the patient's martial status and the number of pregnancies did not appear to have any influence.
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The blood clearances of three platinum compounds, cis-dichlorodiammine platinum II (DDP), cis, trans-dichloro-dihydroxy-bis-(isopropylamine) platinum IV (CHIP), and cis-dichloro-bis-cyclopropylamine platinum II (CP), were determined in nine patients with malignant disease. The complexes were prepared using radioactive platinum (191Pt and 193Pt). A 10-mu Ci dose of each complex, containing the equivalent of 1-2 mg elemental platinum, was injected IV into groups of three patients. Serial blood and urine samples were collected over 72 h. No obvious difference was found between the three complexes for blood clearance, median t1/2a being 16.8 (range 11.2-23.5) min and median t1/2 beta 89 (range 63.7-127) h. The urinary excretion was greatest for CHIP, 60% of injected dose as against 42.6% for CP and 38.8% for DDP. Differences in renal excretion of DDP analogues could indicate potentially less nephrotoxic agents. The use of radioactive Pt will allow in vivo dynamic imaging of the distribution of platinum compounds in areas of interest.
Mouse neuroblastoma cells (Clone NIR-115) were grown in serum-free (defined) medium, defined medium supplemented with serum, and control medium to determine whether serum-free medium could substitute for serum-containing medium in our studies of the histamine H1 and muscarinic acetylcholine receptors of these cells. The function of these receptors as determined by measurement of receptor-mediated cyclic [3H]GMP formation was absent in cells grown in serum-free medium and increased as the percentage of serum was increased in the defined medium, but never attained the levels found with control cells. Muscarinic receptor number for cells grown in defined medium was 60% above that found for control cells with no change in the affinity of the receptor for the radioligand (--)[3H]quinuclidinyl benzilate. Guanylate cyclase and acetylcholinesterase activities for cells grown in defined medium were 23 and 66% of those found in control cells, respectively. This marked reduction of guanylate cyclase activity in large part explains the lack of function of these receptors.
The Leyton Obsessional Inventory was administered to 69 orthopaedic patients in Glasgow, and their responses were compared with those of 77 similar subjects in London and 73 in Cork. The responses of the Scots and the English did not differ, but both of these groups were significantly less obsessional than the Irish subjects, who were particularly likely to regard cleanliness and tidiness as virtues in themselves. Obsessionality was unrelated to age, sex, social class, family size and birth order, but higher Leyton scores were found among bachelors, and among women living in the country and without outside employment. It is suggested that the common factor among these 3 subgroups is emotional or geographic isolation, and that this may enhance any tendency to obsessional ruminations and routines. This could also account for the higher Leyton scores and greater incidence of obsessional neurosis in the Irish.