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Biomedical subjects

M Harrison

Publications and source records attributed to M Harrison.

At least 217 records · Page 12Linked to original sources

Conjunctival and limbal tumours.

One hundred cases of histologically proven corneal and conjunctival tumours were extracted from the records at the Princess Alexandra Hospital and from the senior author's private practice in the last ten years. The tumours were analysed according to Duke-Elder's classification. There were 78 epithelial tumours, 15 pigmented naevi, four melanomas, two dermolipomas and one limbal dermoid. Fourteen of the 41 epithelial carcinomas were followed for three years or more. None of the 14 recurred.

Adult↗

Sheep elastin genes. Isolation and preliminary characterization of a 9.9-kilobase genomic clone.

A sheep genomic library containing sheep DNA in the bacteriophage vector Charon 4A was screened for elastin-gene sequences with partially purified, 32P-labelled elastin mRNA (mRNAE). A recombinant containing a 9.9-kb (kilobase) insert was selected from several positive clones by secondary and tertiary screening for further characterization. Positive identification of this elastin clone, designated SE1, was made with radiolabelled mRNAE by hydridization-selected translation and Southern blotting of restriction-enzyme fragments of SE1 DNA. Hybridization of either mRNAE or elastin complementary DNA to restriction fragments of SE1 showed that most of these fragments of SE1 contained elastin-coding sequences. Orientation of the insert was established by preferential hybridization of a short complementary elastin DNA to restriction fragments adjacent to the right arm of Charon 4A. Reciprocal hybridizations of nick-translated SE1 and sheep genomic DNA on Southern blots showed that two restriction fragments of SE1 contained sequence elements which were repeated at high frequency in a restriction-endonuclease-EcoR1 digest of total sheep genomic DNA. In the accompanying paper [Davidson, Shibahara, Boyd, Mason, Tolstoshev & Crystal (1984) Biochem. J. 220, 653-663], it is shown that a subcloned fragment of this elastin gene quantitatively and specifically hybridized to mRNAE sequences in sheep tissue RNA. Electron microscopy of SE1-mRNAE hybrids indicated the presence of at least seven large R-loops. Measurements of these structures indicated that SE1 is likely to contain less than 2 kb of coding sequence and more than 8 kb of intervening sequence, with an average exon size of 120 base-pairs. Thus the elastin gene is distributed over an extended region of the sheep genome and contains numerous intervening and coding sequences.

Animals↗

Lysine tRNAs from rat liver: lysine tRNA sequences are highly conserved.

The two major lysine tRNAs from rat liver, tRNA2Lys and tRNA5Lys, were sequenced by rapid gel or chromatogram readout methods. The major tRNA2Lys differs from a minor form only by a base pair in positions 29 and 41; both tRNAs have an unidentified nucleotide, U**, in the third position of the anticodon. Although highly related, the major tRNA2Lys and tRNA5Lys differ in four base pairs and four unpaired nucleotides, including the first position of the anticodons, but have the same base pair in positions 29 and 41. The three tRNAs maintain a m2G-U pair in the acceptor stem. Detection of this m2G is in contrast to other reports of lysine tRNAs. Sequences of lysine tRNAs are strongly conserved in higher eukaryotes.

Animals↗

Diazepam tapering in detoxification for high-dose benzodiazepine abuse.

The clinical characteristics and management of patients who abuse high doses of benzodiazepines are not well described. In a prospective open study, 23 subjects who abused high doses of benzodiazepines were admitted for detoxification. Urine or blood test results confirmed benzodiazepine use in all but one subject and multiple drug use in eight (35%). Median benzodiazepine dose was 150 mg (range 40 to 500 mg) of diazepam equivalent. Initial plasma concentrations (diazepam: median = 1245 ng/ml; desmethyldiazepam: median = 2961 ng/ml) were 400% to 800% higher than usual therapeutic concentrations. For detoxification, subjects were given a loading dose of diazepam equal to approximately 40% their reported daily consumption. This was followed with daily tapering of diazepam by 10%. This regimen resulted in a slow and gradual decline in drug concentrations. Withdrawal symptoms were assessed daily. Sixteen subjects completed detoxification in the hospital without complications. One subject became paranoid and confused on day 7 of withdrawal. This was attributed to a too-low initial loading dose and too-rapid tapering, which resulted in rapid drug elimination. Gradual reduction of diazepam dose appears to be an effective and safe approach for detoxifying abusers of high doses of benzodiazepines.

Adult↗

Burst of ethylene upon horizontal placement of tomato seedlings.

Seedlings of Lycopersicon esculentum Mill. cv Rutgers emit a pulse of ethylene during the first 2 to 4 minutes following horizontal placement. Because this burst appears too rapid and brief to be mediated by increase in net activity of 1-aminocyclopropane-1-carboxylic acid synthase, it might result form accelerated transformation of vacuolar 1-aminocyclopropane-1-carboxylic acid to ethylene.

Amino Acids↗

Gall stones and mortality: a study of all gall stone related deaths in a single health district.

In a prospective study of gall stone related deaths in a single Health District, the biliary tract was examined at necropsy in 1701 cases and 8078 death certificates were searched. Gall stones were identified as the cause of death in only 21 cases (0.26%) but in 291 subjects found to have gall stones or cholecystectomy at necropsy, the mortality was 3.4%. The necropsy prevalence of gall stones in the adult population was 17.1% but nine out of 10 subjects with gall stones had not had a cholecystectomy and women were three times more likely to have had their gall stones removed than men. There were five postoperative deaths (mean age 60 years) with an operative mortality for cholecystectomy in the district of 1.2%. Death due to unoperated gall stones was identified in 16 subjects, most of whom were very elderly women (mean age 81) but carcinoma of the gall bladder was only found in one woman of 90 with gall stones. The prevalence of gall stones rose with age in both sexes but the cholecystectomy rate per head of population at-risk declined sharply in the seventh decade in women and the eighth decade in men. There are a large number of people with unoperated gall stones in the population but gall stone related deaths are very uncommon. The cholecystectomy rate in Britain, however, seems to be rising and it is suggested that if this trend continues there may be an increased number of deaths.

Adult↗

Direct demonstration of the human parvovirus in erythroid progenitor cells infected in vitro.

The human parvovirus (HPV), the cause of transient aplastic crisis of hereditary hemolytic anemia, has been shown to be cytotoxic for erythroid progenitor cells and its presence in these cells demonstrated by morphologic techniques. A relatively pure population of progenitors, isolated by removal of immature erythroid bursts from primary culture, was the target of the virus infection. Infected cells failed to proliferate in secondary culture. Using a monoclonal antibody to HPV, specific fluorescence was demonstrated in a minority of cells 24-48 h after infection with virus. Infected cells examined by electron microscopy showed marked toxic ultrastructural alterations and parvovirus-like particles in crystalline arrays in the nucleus.

Antibodies, Monoclonal↗

Perturbation of the mitochondrial lysine tRNA population by virus-induced transformation or stress of mammalian cells: functional properties and nucleotide sequence of a mitochondrially associated lysine tRNA.

Eleven isoaccepting lysine tRNAs from mammalian sources are demonstrable by RPC-5 chromatography and polyacrylamide gel electrophoresis. The appearance and amounts of these isoacceptors varies with the source and growth state of cells. One isoacceptor, tRNALys6, observed in preparations of tRNA from some virus-transformed cells in culture, has been characterized by determining functional properties, cellular location, and its nucleotide sequence. tRNALys6 responds primarily to the lysine codon AAA, but it is not used efficiently in a wheat germ translational system in vitro. Compared with lysine isoacceptors 1, 2, 4, 5a, and 5, [3H]lysine appears in vivo in tRNALys6 with a delay of about 3 h. This delay may in part be a result of a less functional tRNA, but a compartmented state of tRNALys6 also appears to be important. tRNALys6 is associated with mitoplasts prepared from KA31 fibroblasts. The nucleotide sequence of tRNALys6 was determined by rapid postlabeling procedures involving limited hydrolysis in formamide, 32P-labeling of 5' ends of fragments with polynucleotide kinase, separation of the nested set of fragments in polyacrylamide denaturing gels, release of 5'-labeled nucleotides with RNase T2, and identification of the released nucleotides by chromatography on PEI cellulose. Confirmation of the positions of major nucleotides was done by using limited digestions by RNases of tRNALys6 labeled with 32P on the 3' terminus in a gel readout procedure. The nucleotide sequence of tRNALys6 differs from that of cytoplasmic lysine tRNAs and mammalian mitochondrial lysine tRNAs. It contains U*, an unidentified modified uridine occurring in the anticodon of some mitochondrial tRNAs. tRNALys6 appears to occur in very limited amounts, or not at all, in most cells unless stressed, but when present it is associated with mitochondria, although it is probably coded in the nucleus.

Animals↗

Diazepam loading: simplified treatment of alcohol withdrawal.

Alcohol withdrawal therapy can be simplified with a loading dose of diazepam, taking advantage of the kinetic tapering afforded by the drug's long t 1/2s and its metabolites, and of the effectiveness of nonpharmacologic maneuvers. In a double-blind trial, 50 inpatients in moderate to severe alcohol withdrawal received 20 mg oral diazepam and supportive care (n = 25) or placebo and supportive care (n = 25) every 2 hr until they were asymptomatic. Fifty-six percent of patients responded to placebo within 5 +/- 2.9 hr (mean +/- SD), whereas 72% responded to initial diazepam within 6.3 +/- 3.9 hr. Patients treated with diazepam had more rapid and greater improvement than those treated with placebo. Patients who did not respond to six doses of diazepam received further (unblinded) diazepam, 20 mg, every 1 to 2 hr. All patients who did not initially respond (n = 18) improved after more diazepam. Thus all patients who received diazepam (n = 36), during the experimental phase or subsequently, were effectively treated. There were no adverse effects. The median number of 20-mg diazepam doses to treat alcohol withdrawal were three, given over a period of 7.6 hr (range = 1 to 12 and 0.33 to 45 hr). Complications occurred only in those who received placebo during the experimental phase, indicating that delay in therapy may be responsible for the appearance of complications in alcohol withdrawal.

Adult↗

Aminooxyacetate stimulation of glycolate formation and excretion by chlamydomonas.

Aminooxyacetate (1 millimolar) did not inhibit photosynthetic (14)CO(2) fixation by Chlamydomonas reinhardtii Dangeard, (-) strain (N.90) but greatly stimulated the biosynthesis and excretion of glycolate. Similar results were obtained from cells grown with 5% CO(2) or low CO(2) (air). After 2 minutes with air-grown cells, [(14)C]glycolate increased from 0.3% of the total (14)C fixed by the control to 11.7% in the presence of aminooxyacetate and after 10 minutes from 3.8% to 41.1%. Ammonium nitrate (0.2 millimolar) in the media blocked the aminooxyacetate stimulation of glycolate excretion. Chromatographic analyses of the labeled products in the cells and supernatant media indicated that aminooxyacetate also completely inhibited the labeling of alanine while some pyruvate accumulated and was excreted. A high percentage (35%) of initial (14)CO(2) fixation was into C(4) acids. Initial products of (14)CO(2) fixation included phosphate esters as well as malate, aspartate, and glutamate in treated or untreated cells. Lactate was also a major early product of photosynthesis, and its labeling was reduced by aminooxyacetate. Inasmuch as lactate was not excreted, glycolate excretion seemed to be specific. When photosynthesis was inhibited by 3-(3,4-dichlorophenyl)-1,1-dimethylurea, labeled organic and amino acids but not phosphate esters were lost from the cells. Aminooxyacetate did not inhibit the enzymes associated with glycolate synthesis from ribulose bisphosphate.

Journal Article↗

Metronidazole v. cefoxitin in severe appendicitis--a trial to compare a single intraoperative dose of two antibiotics given intravenously.

In severe appendicitis, the effect of a single intravenous dose of metronidazole (500 mg) was compared with cefoxitin (1 g). The antibiotics were given by random allocation once the diagnosis had been established at operation. In the metronidazole group, 5 out of 48 patients developed a wound infection whilst in hospital compared with 13 out of 48 in the cefoxitin group (P = 0.036). However, 57% of wound infections became apparent after the patient went home and the overall infection rates were similar. The mean length of postoperative hospital stay was 5.0 days in the metronidazole group and 6.8 days in the cefoxitin group (P = 0.052), but of those who did develop a wound infection, the length of stay was almost double in the cefoxitin group. Anaerobic organisms were cultured from the wound in 7 out of 15 patients who received cefoxitin but in none of 5 patients in the metronidazole group. Whilst metronidazole only delayed the discharge of pus from the wound, it did seem to reduce the severity of infection. Cefoxitin appeared to be less effective, given as a single intravenous injection at a dose of 1 g.

Adult↗

Clinical trial of iohexol in lumbar myelography.

Iohexol containing 180 mg I/ml was used in 20 patients for lumbar myelography. By using an adequate volume up to a maximum of 15 ml, satisfactory films were obtained in all cases. Minor or moderate adverse effects occurred in 4 patients. There were no changes in vital signs or neurologic examination related to the examinations. No patient had difficulty with concentration, personality changes or seizures. Later encephalographies performed in all patients before and during 24 h after the iohexol injections, showed no seizure or abnormal activity or any significant change. Repeated lumbar puncture was performed in 9 patients 24 h after the injection of iohexol. One of these, a patient with symptoms due to disc prolapse, whose CSF was abnormal before the myelography, had a slightly increased cellular response. There was no significant change in any of the other patients. Iohexol is a very satisfactory contrast medium for myelography and compared favorably with other non-ionic contrast media.

Adult↗

Clinical trial of iohexol for lumbar myelography.

Iohexol containing 180 mg I/ml was used in 80 patients for myelography by lumbar injection. By using an adequate volume, between 10 and 20 ml, satisfactory films were obtained in all cases. Minor adverse effects occurred in 12 patients (15%) and were more frequent in women than men; they were headache (5), nausea (3), vomiting (2), back or limb pain (5), and skin rash (1) and were of minor degree in 10 cases, moderate in the other two and lasted more than 24 h in only one case. There was no change in vital signs or neurological examination related to the studies. No patient suffered difficulty with concentration, personality change or seizures. Electroencephalograms performed on 21 patients before and during the 24 h after iohexol showed no seizure or focal activity or any significant change. Repeat lumbar punctures were performed on ten patients during the 24 h following myelography. One of these, a patient with symptoms due to disc prolapse, whose CSF was abnormal prior to the myelogram, showed a slightly increased cellular response. There was no significant change in any other case. Iohexol is a very satisfactory contrast medium for myelography and compares favourably with other non-ionic contrast media.

Adolescent↗

Intronless human dihydrofolate reductase genes are derived from processed RNA molecules.

Three groups of recombinant bacteriophage containing coding sequences for dihydrofolate reductase (DHFR; tetrahydrofolate dehydrogenase; 5,6,7,8-tetrahydrofolate:NADP+ oxidoreductase, EC 1.5.1.3) were isolated from two human DNA clone libraries. One recombinant (lambda hDHFR-1) contains three exons that encode the COOH-terminal portion of human DHFR. The other two human DHFR genes (hDHFR-psi 1 and hDHRF-psi 2) lack introns. hDHFR-psi 2 contains several in-phase termination codons and is only 93% homologous to the normal human DHFR coding sequences, whereas hDHFR-psi 1 has an open reading frame and is virtually identical to the coding sequence of the normal DHFR gene. The region of DNA sequence homology between each intronless gene and the normal DHFR gene extends 2.9 kilobases beyond the end of the coding sequences. At the 3' end of this homologous sequence, each intronless gene has an A-rich tract. The lack of introns and the presence of the 3' A-rich tract suggest that hDHFR-psi 1 and hDHFR-psi 2 were derived from processed RNA molecules. A short DNA sequence, 60 nucleotides 5' to the ATG start codon in lambda hDHFR-psi 2, is directly repeated immediately after the 3' A-rich tract; such terminal direct repeats also flank integrated proretroviruses and transposable DNA elements and are thought to be the hallmark of inserted DNA sequences.

Base Sequence↗