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Biomedical subjects

T Porter

Publications and source records attributed to T Porter.

At least 37 records · Page 2Linked to original sources
PubMed1995

Modification of therapy based on videourodynamics in neurologically normal children: Southampton 1988-1993.

OBJECTIVE: To follow up a previously investigated group of enuretic children to assess their current situation and to determine if their previous treatment was appropriate. PATIENTS AND METHODS: A group of 57 neurologically normal, enuretic children (mean age 10 years) were followed for a mean of 19 months (range 3-54) after the establishment of a working diagnosis with videourodynamics. Many of these children had previously been under medical follow-up for long periods with no change in their enuresis. Depending on the urodynamic diagnosis, a therapeutic strategy was instigated and continued for an appropriate duration. Normal children were simply reassured. RESULTS: Currently, 44 patients (77%) are completely or very nearly dry. CONCLUSION: Videourodynamics, although a traumatic procedure, provides information unobtainable from other sources. Treatment based on this information gives good results and may prevent years of unnecessary or inappropriate therapy, and psychological problems. Ambulatory studies may yield more useful information.

Child↗
PubMed1994

Can total thyroidectomy be performed as safely by general surgeons in provincial centers as by surgeons in specialized endocrine surgical units? Making the case for surgical training.

OBJECTIVE: To determine whether surgeons who had received appropriate training in the technique of total thyroidectomy could continue to perform the procedure with minimal morbidity after moving to a provincial surgical practice. DESIGN: Comparison of the complication rates from total thyroidectomy between a specialized endocrine surgical unit and provincial centers. SETTING AND PATIENTS: Six hundred fifty patients undergoing total thyroidectomy by two surgeons over a 5-year period in the endocrine surgical unit at Royal North Shore Hospital, St Leonards, Australia, were compared with 120 patients undergoing total thyroidectomy by seven provincial surgeons who were former trainees in the unit. MAIN OUTCOME MEASURES: Indications for surgery and specific complications of thyroidectomy including recurrent laryngeal nerve palsy, permanent hypoparathyroidism, and postoperative bleeding. RESULTS: Each of the seven surgeons in provincial practice performed only between two and 16 thyroidectomies annually. The percentage of total thyroidectomies for benign and malignant disease was identical for both the endocrine surgical unit and provincial center groups (44%). There was no difference in the incidence of recurrent laryngeal nerve palsy, permanent hypoparathyroidism, or postoperative bleeding between the two groups. CONCLUSION: Total thyroidectomy is an operation that always engenders controversy relating to the morbidity of recurrent laryngeal nerve and parathyroid injury. Surgeons who have completed a well-designed training program and who have become proficient at total thyroidectomy as trainees will remain proficient at the procedure despite practicing in a provincial center. Achieving a low morbidity rate demands meticulous attention to operative technique and anatomical detail.

Clinical Competence↗
PubMed1994

EMG and cardiovascular responses to emotionally provocative photographs and text.

Previous studies on the psychophysiology of human emotion have repeatedly shown general and occasionally specific facial EMG (mu v) and covert cardiovascular response relationships to emotionally provocative photographs. Less clear are the relationships between psychophysiological response indices measured during the silent reading of emotionally charged versus emotionally neutral text. In this study, 12 adult subjects were presented two emotionally loaded color and black-and-white photographs and two brief newspaper articles, one emotionally charged and the other emotionally neutral in content. Each independent stimulus was presented for 1 min., preceded by a rest according to a multiple baseline-reversal design. Subjects evaluated each pictorial and textual stimulus condition according to adjective dimensions on 7-point rating scales. Mean values for corrugator supercilii EMG (mu v), upper trapezius EMG (mu v), surface temperature (degrees F), and heart rate (bpm) measured by finger photoplethysmography were measured during each rest and test period. Significant increases in the subjects' mean corrugator supercilii EMG (mu v) measures were observed during all color and black-and-white photograph presentations for both emotional and neutral content. As predicted, the subjects' mean corrugator supercilii EMG (mu v) measures increased significantly while silently reading text with an obvious unpleasant emotional tone. A significant positive relationship was observed between the subjects' mean ratings and mean corrugator EMG (mu v) difference values for the emotionally loaded color photographs.

Adult↗
PubMed1993

Mapping of neutralizing epitopes and the receptor binding site of human interleukin 1 beta.

Antibodies to synthetic peptides of human interleukin 1 beta (IL-1 beta) and to recombinant human IL-1 beta were used to identify epitopes of IL-1 beta associated with the neutralization of its biological activity. Analysis of antisera raised to 17 synthetic peptides derived from the mature IL-1 beta sequence showed that five regions (residues 6-15, 49-80, 58-80, 92-101, and 120-133) were both immunoprecipitating and neutralizing. Using a hexamer epitope mapping method, comparison of the regions recognized by four neutralizing rabbit antisera with those recognized by a rabbit antiserum raised to denatured IL-1 beta suggested two further neutralizing epitopes, residues 39-48 and 83-95. Finally, a neutralizing monoclonal antibody was shown to bind to the peptides 6-11 and 87-95 by peptide binding and mutagenesis. All of these regions appear predominantly on one face of IL-1 beta. The effect of mutations in residues 4-11 and 88-97, which lie within this face, on receptor binding and biological activity was determined. Most of the mutations tested affected both receptor binding and activity, whereas mutations in another face of IL-1 beta (residues 74-80) had no effect. Purification of two of the mutants with reduced bioactivity and receptor binding and analysis by two-dimensional NMR indicated no gross changes in tertiary structure. A third mutant had reduced bioactivity in two different bioassays but no change in receptor binding. Although two-dimensional NMR revealed no gross changes in conformation, small changes did occur at a site distal from that mutated. The data are consistent with other epitope mapping and receptor binding mutagenesis data and suggest that the neutralizing antibodies and receptor recognize different but overlapping regions of IL-1 beta.

Amino Acid Sequence↗
PubMed1993

Targeting vector configuration and method of gene transfer influence targeted correction of the APRT gene in Chinese hamster ovary cells.

A 21-bp deletion in the third exon of the APRT gene in Chinese hamster ovary (CHO) cells was corrected by transfection with a plasmid containing hamster APRT sequences. Targeted correction frequencies in the range of 0.3-3.0 x 10(-6) were obtained with a vector containing 3.2 kb of APRT sequence homology. To examine the influence of vector configuration on targeted gene correction, a double-strand break was introduced at one of two positions in the vector prior to transfection by calcium phosphate-DNA coprecipitation or electroporation. A double-strand break in the region of APRT homology contained in the vector produced an insertion-type vector, while placement of the break just outside the region of homology produced a replacement-type vector. Gene targeting with both linear vector configurations yielded equivalent ratios of targeted recombinants to nontargeted vector integrants; however, targeting with the two different vector configurations resulted in different distributions of targeted recombination products. Analysis of 66 independent APRT+ recombinant clones by Southern hybridization showed that targeting with the vector in a replacement-type configuration yielded fewer targeted integrants and more target gene convertants than did the integration vector configuration. Targeted recombination was about fivefold more efficient with electroporation than with calcium phosphate-DNA coprecipitation; however, both gene transfer methods produced similar distributions of targeted recombinants, which depended only on targeting vector configuration. Our results demonstrate that insertion-type and replacement-type gene targeting vectors produce similar overall targeting frequencies in gene correction experiments, but that vector configuration can significantly influence the yield of particular recombinant types.

Adenine Phosphoribosyltransferase↗
PubMed1990

A novel selection system for recombinational and mutational events within an intron of a eucaryotic gene.

In order to identify a poison sequence that might be useful in studying illegitimate recombination of mammalian cell chromosomes, several DNA segments were tested for their ability to interfere with gene expression when placed in an intron. A tRNA gene and its flanking sequences (267 bp) were shown to inhibit SV40 plaque formation 100-fold, when inserted into the intron in the T-antigen gene. Similarly, when the same DNA segment was placed in the second intron of the adenosine phosphoribosyl transferase (APRT) gene from CHO cells, it inhibited transformation of APRT-CHO cells 500-fold. These two tests indicated that the 267-bp DNA segment contained a poison sequence. The poison sequence did not affect replication since the replication of poisoned SV40 genomes was complemented by viable SV40 genomes and poisoned APRT genes were stably integrated into cell chromosomes. Cleavage of the poison sequence in the SV40 T-antigen intron by restriction enzymes indicated that the tRNA structural sequences and the 5' flanking sequences were not required for inhibition of SV40 plaque formation. Sequence analysis of viable mutant SV40, which arose after transfection of poisoned genomes, localized the poison sequence to a 35 bp segment immediately 3' of the tRNA structural sequences.

Adenine Phosphoribosyltransferase↗
PubMed1989

Effect of chronic maternal drug addiction on placental drug metabolism.

Microsomes were prepared from the term placentas of 5 drug-dependent and 4 normal (control) mothers and from the livers of 3 normal fetuses (gestational age = 22-24 weeks) to determine if chronic maternal drug addiction can induce metabolic pathways in the placenta which are utilized in the biotransformation of drugs of abuse. Using as model substrates aminopyrine for demethylation, aniline for hydroxylation, and bilirubin for conjugation, we observed little to none of substrate biotransformation in both drug-dependent and control placentas. Similarly, such enzymatic activity in the fetal liver was also low. We conclude that chronic maternal addiction does not induce metabolic pathways in the placenta for the biotransformation of drugs of abuse.

Biotransformation↗
PubMed1986

Influence of breast-feeding on the restoration of the low serum concentration of vitamin E and beta-carotene in the newborn infant.

Vitamin E and beta-carotene are two important natural antioxidants. However, the mean (+/- SD) serum concentrations of beta-carotene in the cord blood of term (17.9 +/- 4.4 micrograms/dl) and preterm (14.04 +/- 4.7 micrograms/dl) infants are one eighth the concentration in the maternal serum (131 +/- 43 micrograms/dl). Likewise the serum concentrations of vitamin E in the term (0.31 +/- 0.09 mg/dl) and preterm (0.29 +/- 0.08 mg/dl) infants are one-third the concentration in the maternal serum (0.97 +/- 0.16 mg/dl). Human breast milk, particularly colostrum, contains very high concentrations of both vitamin E (3.28 +/- 2.93 mg/dl) and beta-carotene (213 +/- 166 micrograms/dl). Thus the breast-fed, term infant attains serum levels of both vitamin E and beta-carotene comparable to those in the adult within 4 to 6 days of breast-feeding. This study shows that the seeming barrier in the fetus to access to the antioxidants vitamin E and beta-carotene, in rapidly corrected and the substances are replenished postnatally through breast-feeding. This study therefore alludes to the possible role of breast-feeding in providing for the infant's defense against oxygen toxicity.

Antioxidants↗
PubMed1984

Peripheral nerve extract promotes long-term survival and neurite outgrowth in cultured spinal cord neurons.

The hypothesis that peripheral, skeletal muscle tissue contains a trophic factor supporting central neurons has recently been investigated in vitro by supplementing the culture medium of spinal cord neurons with muscle extracts and fractions of extract. We extended these studies asking whether or not a trophic factor is present in peripheral nerves, the connecting link between muscle and central neurons via which factors may be translocated from muscle to neurons by the retrograde transport system. Lumbar, 8-day-old chick spinal cords were dissociated into single cells and then cultured in the presence of peripheral nerve extract. Cytosine arabinoside was added to inhibit proliferation of nonneuronal cells. In the presence of nerve extract, spinal cord neurons survived for more than a month, extended numerous neurites, and showed activity of choline acetyltransferase. In the absence of extract, neurons attached and survived for a few days but then died subsequently in less than 10 days. Neurite outgrowth did not occur in the absence of extract. Withdrawal of extract from the medium of established neuronal cultures caused progressive loss of both cells and neurites. Other tissues also contained neuron supporting activity but less than that found in nerve extract. These studies indicate that peripheral nerves contain relatively high levels of spinal cord neuron-directed trophic activity, suggesting translocation of neurotrophic factor from muscle to central target neurons. The neurotrophic factor has long-term (weeks) effects, whereas short-term (days) survival is factor independent.

Animals↗
PubMed1984

How damaged is the biologically active subpopulation of transfected DNA?

Relatively little is known about the damage suffered by transfected DNA molecules during their journey from outside the cell into the nucleus. To follow selectively the minor subpopulation that completes this journey, we devised a genetic approach using simian virus 40 DNA transfected with DEAE-dextran. We investigated this active subpopulation in three ways: (i) by assaying reciprocal pairs of mutant linear dimers which differed only in the arrangement of two mutant genomes; (ii) by assaying a series of wild-type oligomers which ranged from 1.1 to 2.0 simian virus 40 genomes in length; and (iii) by assaying linear monomers of simian virus 40 which were cleaved within a nonessential region to leave either sticky, blunt, or mismatched ends. We conclude from these studies that transfected DNA molecules in the active subpopulation are moderately damaged by fragmentation and modification of ends. As a whole, the active subpopulation suffers about one break per 5 to 15 kilobases, and about 15 to 20% of the molecules have one or both ends modified. Our analysis of fragmentation is consistent with the random introduction of double-strand breaks, whose cause and exact nature are unknown. Our analysis of end modification indicated that the most prevalent form of damage involved deletion or addition of less than 25 base pairs. In addition we demonstrated directly that the efficiencies of joining sticky, blunt, or mismatched ends are identical, verifying the apparent ability of cells to join nearly any two DNA ends and suggesting that the efficiency of joining approaches 100%. The design of these experiments ensured that the detected damage preceded viral replication and thus should be common to all DNAs transfected with DEAE-dextran and not specific for viral DNA. These measurements of damage within transfected DNA have important consequences for studies of homologous and nonhomologous recombination in somatic cells as is discussed.

Animals↗
PubMed1982

Identification of two different Q-binding sites in QH2-cytochrome c oxidoreductase, using the Q analogue n-heptadecylmercapto-6-hydroxy-5,8-quinolinequinone.

The pK and mid-point redox potential of the Q-analogue 7-(n-heptadecyl)mercapto-6-hydroxy-5,8-quinolinequinone (HMHQQ) in aqueous medium are so low that under the experimental conditions used for studying the inhibition of electron transfer in submitochondrial particles only the oxidized, anionic form is present. The KD of the analogue, determined by comparing its inhibitory effect with that of n-heptyl-4-hydroxyquinoline N-oxide, is (0.003 + 0.24 x mg protein/ml) microM. The inhibition of succinate oxidation is pH dependent, due to a pH-dependent change in the overcapacity of the QH2-oxidizing system above the Q-reducing system. If the terminal part of the respiratory chain is reduced with ascorbate, the analogue inhibits the reduction of cytochrome b by substrate in the presence of antimycin with a similar KD value. In the absence of ascorbate the KD value is 100-times higher. The reduction of cytochrome b by substrate in particles treated with 2,3-dimercaptopropanol (BAL) + O2 is also sensitive to HMHQQ, with a KD value in between the two values given above. It is concluded that the QH2 oxidase system contains two different sites for interaction with ubiquinone. The site responsible for the inhibition of steady-state electron transfer is near the Fe-S cluster, as is shown by the sensitivity to the redox state of this cluster and by the effect of HMHQQ on the EPR signal of the reduced cluster. The second site, which is similar to the antimycin-binding site, is occupied only at higher concentrations of inhibitor. The affinity of HMHQQ for this site is not affected by the redox state of the Fe-S cluster.

Animals↗