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Biomedical subjects

S Freeman

Publications and source records attributed to S Freeman.

At least 37 records · Page 2Linked to original sources
PubMed1990

Nondisjunction of chromosome 21.

Chromosome heteromorphisms and restriction fragment length polymorphisms were used to study the origin of the extra chromosome in 54 trisomy 21 conceptuses. The parental origin was determined in 43 cases, with 39 (91%) being maternally and 4 (9%) parentally derived. Analysis of recombination demonstrated the presence of one or two cross-overs in most cases for which sufficient information was available, suggesting that failure to pair/exchange at meiosis I is relatively unimportant in the genesis of trisomy 21.

Adult↗
PubMed1990

The influence of sound stimulus parameters on the acoustic reflex waveform.

The transient increase in admittance seen at the beginning of the acoustic reflex response in man was investigated with a view to reaching a better understanding of its possible mechanisms. The sound stimulus intensity, its duration and its off-time were varied to investigate their effects on the morphology of the admittance waveform. The results found suggest that the transient increase may not be due to a temporary partial decoupling of the ossicular chain during the initial stages of stapedial contraction, but rather that it may be caused by a slight improvement in the coupling between the middle ear components.

Acoustic Stimulation↗
PubMed1990

Evoked potential changes in cats following injection of an extract from the venom sac of the oriental hornet (Vespa orientalis).

Venom sac extract from the hornet Vespa orientalis was injected (via the subclavian artery) into cats and its effects on evoked potentials in two different sensory pathways (auditory and somatosensory) was investigated. A comparison was made between the venom sac extract from adult hornets and that from young (0-24 hr of age) hornets. There was a bimodal change in blood pressure, a hypothermic effect and a decrease in amplitude of the last waves of the auditory and somato sensory pathways when venom sac extract of adult hornets was injected. Venom sac extract from young hornet workers had the same influence on the blood pressure, did not affect thermoregulation and the effect on the auditory and somato sensory pathways were less consistent. Adult venom sac extract had mainly a central effect whilst the venom sac extract from young hornets (in larger doses) affected the central and/or peripheral nervous system. The central effects could be interpreted as due to opening of the blood-brain barrier by the venom.

Animals↗
PubMed1990

Reticular erythema with ostial porokeratosis.

An asymptomatic reticular erythema associated with myriads of monomorphous micropapules developed in a symmetric distribution concentrated on the inner aspects of both arms and both legs of a 15-year-old girl. Skin biopsy specimens revealed cornoid lamellae within multiple appendageal ostia and focal lymphocytic inflammation in the papillary dermis. Reticular erythema with ostial porokeratosis is one of an increasing number of clinical presentations of punctate porokeratosis that lack a classic marginated rim.

Adolescent↗
PubMed1990

Vestibular evoked potentials with short and middle latencies recorded in humans.

Following success in recording short latency vestibular evoked potentials in experimental animals, we have succeeded in our attempts to record such potentials in human subjects. The stimuli were repetitive, short steps of high intensity angular acceleration (10,000 degrees/sec2) with short rise times which would synchronously activate many neurons of the vestibular pathway. Stringent control procedures ensured that the recorded activity was not an artefact. Short latency vestibular evoked potentials were recorded in 10 normal subjects with peak latencies of 3.5, 6.0 and 8.4 msec and amplitudes of 0.5 microV. Middle latency potentials were also recorded with latencies of 8.8, 18.8 and 26.8 msec and amplitudes of 15 microV. These responses were absent in a cadaver and in patients with bilateral dead labyrinths. In normal subjects, these vestibular evoked potentials were not affected by white noise. In conclusion, short and middle latency vestibular evoked potentials were recorded in normal human subjects.

Adolescent↗
PubMed1990

Human gene transfer: characterization of human tumor-infiltrating lymphocytes as vehicles for retroviral-mediated gene transfer in man.

Tumor-infiltrating lymphocytes (TILs) are cells generated from tumor suspensions cultured in interleukin 2 that can mediate cancer regression when adoptively transferred into mice or humans. Since TILs proliferate rapidly in vitro, recirculate, and preferentially localize at the tumor site in vivo, they provide an attractive model for delivery of exogenous genetic material into man. To determine whether efficient gene transfer into TILs is feasible, we transduced human TILs with the bacterial gene for neomycin-resistance (NeoR) using the retroviral vector N2. The transduced TIL populations were stable and polyclonal with respect to the intact NeoR gene integration and expressed high levels of neomycin phosphotransferase activity. The NeoR gene insertion did not alter the in vitro growth pattern and interleukin 2 dependence of the transduced TILs. Analyses of T-cell receptor gene rearrangement for beta- and gamma-chain genes revealed the oligoclonal nature of the TIL populations with no major change in the DNA rearrangement patterns or the levels of mRNA expression of the beta and gamma chains following transduction and selection of TILs in the neomycin analog G418. Human TILs expressed mRNA for tumor necrosis factors (alpha and beta) and interleukin 2 receptor P55 but not for interleukin 1 beta, granulocyte/macrophage colony-stimulating factor, interleukin 6, and interferon gamma when grown with high-dose interleukin 2 without subsequent activation with mitogen or specific antigen. This pattern of cytokine-mRNA expression was not significantly altered following the transduction of TILs. The NeoR gene-transduced TILs could thus be used to follow the trafficking and survival of TILs in vivo, and clinical protocols using these transduced TILs in cancer patients have begun. The studies demonstrate the feasibility of TILs as suitable cellular vehicles for the introduction of therapeutic genes into patients receiving autologous TILs.

Biological Factors↗
PubMed1989

ABR threshold is a function of blood oxygen level.

In order to determine if there is a relation between auditory threshold and oxygen availability, cats were anesthetized, paralyzed and ventilated with room air and with hypoxic gas mixtures. Auditory nerve-brain stem evoked response (ABR) thresholds and arterial blood oxygen levels [partial pressures (PaO2) and percent saturation (SaO2)] were determined. The ABR threshold was unchanged as long as PaO2 was above 30 mm Hg (SaO2 greater than 45%). Below PaO2 20 mmHg (SaO2 less than 25%) the animal was not viable. Between these values, the hypoxia caused ABR threshold elevations which were reversible when the animal was again respirated with room air. ABR threshold was an inverse function of blood O2 level with an approximate 3.05 dB elevation for every mmHg decrease in PaO2 (2.89 dB/% SaO2). These findings are probably due to hypoxia induced depression of the endocochlear potential. Since ABR could be recorded in premature human neonates after at least 28 weeks gestation and since the human fetus in utero is also hypoxic, these results indicate that the fetus (greater than 28 weeks gestational age) has a sensorineural hearing loss in addition to a conductive loss.

Animals↗
PubMed1989

Controlled clinical trial of adjuvant immunotherapy with BCG and neuraminidase-treated autologous tumour cells in large bowel cancer.

A controlled, randomised clinical trial of immunotherapy was performed in 301 patients with stage B or C colorectal cancer. The immunotherapy treatment consisted of 18 vaccinations over a 2 year period following surgery with a combination of BCG given by scarification plus subcutaneous injection of Vibrio cholera neuraminidase (VCN)-modified autologous tumour cells. Five year follow-up has now been completed in all patients. The immunotherapy did not alter either the disease-free interval or the overall survival of patients in comparison with a control group of patients not receiving immunotherapy.

Adenocarcinoma↗
PubMed1989

Influence of infusion time on unchanged cisplatin disposition in patients with ovarian cancer.

The disposition of unchanged cisplatin in ten patients with ovarian cancer receiving 2-h infusions of 100 mg/m2 was compared with that of ten patients receiving 6-h infusions. A high-performance liquid chromatographic assay specific for the unchanged drug was used and all collected samples were rapidly processed. Patients were catheterized for urine collections. Cisplatin renal clearance was significantly lower after 6-hour infusions (52.8 +/- 16.2 ml/min per m2) than after 2-h infusions (87.1 +/- 38.2 ml/min per m2) (P = 0.026). Total clearance was also lower and less variable, although not significantly, in patients receiving the longer infusion. No differences in nonrenal clearance, volume of distribution, or half-life were observed between the two groups. There was only a poor relationship between cisplatin renal clearance and creatinine clearance after 2-h (r2 = 0.02; P = 0.66) and 6-h infusions (r2 = 0.18; P = 0.23). A single cisplatin plasma level obtained at the end of the infusion proved to be a good predictor of total cisplatin clearance after both 2-h (r2 = 0.70; P = 0.0096) and 6-h infusions (r2 = 0.97; P = 0.0001). This level was not significantly related to the relatively small changes in creatinine clearance that occurred after three courses of treatment.

Aged↗
PubMed1989

EEG mean frequencies are sensitive indices of phenylalanine effects on normal brain.

We previously reported that changes in plasma phenylalanine (PHE) concentrations of 1000 microM or more adversely affected cognitive function and reduced mean frequency of the EEG power spectrum. In the present study, we characterized EEG effects of changes in plasma PHE from physiological to supraphysiological concentrations. Subjects were mentally normal children and adult volunteers with 3 different genotypes for phenylalanine hydroxylase (PHY): homozygous deficient, heterozygous, and homozygous normal. Double-blinded crossover studies were performed at equilibrium during PHE restriction and supplementation. The mean frequency of the power spectrum and the mean across a set of alpha-theta factors showed highly significant, reversible, generalized EEG slowing during PHE supplementation in subjects homozygous for PHY deficiency. Smaller but significant changes in EEG mean frequencies occurred in the heterozygous and normal subjects. Spectral profiles of EEG change were similar in both groups; the mean alpha-theta was more sensitive in the second group. Demonstration of EEG changes with PHE supplementation in normal individuals has important dietary implications.

Adult↗
PubMed1989

Tendency to irritation: sensitive skin.

The plausibility of the concept of "sensitive skin" evokes discussion and often amusement, because of the variance of the number of opinions compared with the amount of data, at least until recently. This report presents recent biologically oriented data that suggest that sensitive skin is a reality and is assessable with the use of contemporary methods.

Body Water↗
PubMed1989

Phaeohyphomycosis due to Phialophora richardsiae.

Phaeohyphomycosis, an infection characterised by dematiaceous yeast-like cells, hyphae and pseudohyphae in tissue, is an uncommon condition, often affecting immunosuppressed patients. A sixty four year old boat-builder, receiving treatment with prednisone and azathioprine developed multiple cutaneous nodules on the extremities. Histology showed a mixed dermal inflammatory infiltrate with scattered spores and hyphae. Culture revealed two organisms, Phialophora richardsiae and Exophiala jeanselmei. Fluorocytosine was initially given but the organism was found to be resistant. Since side effects have been associated with long term ketoconazole therapy, a less toxic and more potent triazole compound, itraconazole, was used. After three months, the lesions had completely resolved without adverse clinical or biochemical changes.

Antifungal Agents↗
PubMed1989

Two- versus 24-hour infusion of cisplatin: pharmacokinetic considerations.

The disposition of unchanged cisplatin was compared after two- and 24-hour intravenous (IV) infusion to eight patients with germ cell cancer (dose, 100 mg/m2), 14 patients with head and neck cancer (dose, seven patients 50 mg/m2; seven patients, 100 mg/m2). Patients were randomized to receive either a two- or 24-hour infusion in the first course of treatment and the reverse in the second course. Cisplatin renal clearance, total clearance, and the percentage of the dose excreted unchanged in urine were significantly lower with the longer infusion. Total clearance was 345 +/- 97.0 mL/min/m2 after the two-hour infusion and 268 +/- 70.7 mL/min/m2 after the 24-hour infusion (P less than .0001). Renal clearance was 79.1 +/- 35.3 mL/min/m2 and 34.1 +/- 14.9 mL/min/m2 (P less than .0001). The percentage of the dose excreted unchanged in urine was 22.9 +/- 6.5% and 12.8 +/- 4.0%, respectively (P less than .0001). The ratio of cisplatin renal clearance to creatinine clearance was 1.95 +/- .96 after the two-hour infusion and .90 +/- .40 after the 24-hour infusion (P less than .001). There was only a poor relationship between cisplatin renal clearance and creatinine clearance after a two-hour infusion (r2 = .05, P greater than .1) or 24-hour infusion (r2 = .18, P greater than .05). The severity of emesis was graded on a four-point scale and was significantly less with the 24-hour infusion than with the two-hour infusion (P less than .05). Twenty-four-hour infusion of cisplatin resulted in greater drug retention in patients due to reduced renal clearance, but was also associated with reduced emetic toxicity, probably as a result of lower peak plasma levels.

Adolescent↗
PubMed1988

The stereochemical course of phospho group transfer catalyzed by rat liver 6-phosphofructo-2-kinase.

Adenosine [gamma-(S)-16O,17O,18O]triphosphate was used as substrate in the phosphokinase reaction catalyzed by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. The product D-fructose 2,6-[2-16O,17O,18O]bisphosphate was then used as substrate in the alkaline phosphatase-mediated transfer of the phospho groups to (S)-butane-1,3-diol, where the configuration at phosphorus has been determined. Although there was approximately equal transfer by alkaline phosphatase of the labeled 2- and the unlabeled 6-phospho groups, the subsequent assignment of configuration of the chiral phospho group from the 2-position was unambiguous. It was found that 6-phosphofructo-2-kinase proceeds by a pathway that results in net inversion of the configuration at phosphorus. The simplest interpretation of this result is that the phospho group is transferred directly between substrates in a ternary complex by an "in-line" mechanism not involving a phosphoenzyme intermediate. This conclusion is consistent with the fact that the enzyme cannot be labeled by [gamma-32P]ATP and with steady-state kinetic data that suggest an ordered sequential mechanism. This finding also indicates that the adenine nucleotide and sugar phosphate isotope exchange reactions catalyzed by the enzyme are not relevant to the normal catalytic pathway of the kinase.

Adenosine Triphosphate↗
PubMed1988

Phosphonate biosynthesis: isolation of the enzyme responsible for the formation of a carbon-phosphorus bond.

The first isolation of a naturally occurring phosphonate in 1959 led rapidly to the discovery of a variety of metabolites containing a phosphorus-carbon bond. Phosphonates have been found in bacteria, fungi, and higher organisms such as the snail schistosome vector Biomphalaria. The biosynthetic path to the P-C bond has, however, remained undefined. Thus although it was shown twenty years ago that the isotope label from [14C]glucose or from [32P]phosphoenolpyruvate is incorporated into 2-aminoethylphosphonate by the protozoan Tetrahymena pyriformis, the presumed stoichiometric transformation of phosphoenolpyruvate to phosphonopyruvate has never been demonstrated. Low conversions of phosphoenolpyruvate into 2-aminoethylphosphonate and the trapping of phosphonopyruvate from phosphoenolpyruvate have been reported, but these reactions have not proved reproducible, and the existence of the critical enzyme, phosphoenolpyruvate phosphonomutase, has remained notional. We now report experiments that resolve this enigma, and describe the isolation and characterization of the pure mutase from T. pyriformis.

Amino Acid Sequence↗
PubMed1988

Stereochemistry of phospho group transfer catalyzed by a mutant alkaline phosphatase.

The stereochemical course of the phospho group transfer catalyzed by mutant (S102C) alkaline phosphatase from Escherichia coli was investigated by using 31P nuclear magnetic resonance spectroscopy. Transphosphorylation from 4-nitrophenyl (Rp)-[16O, 17O, 18O]phosphate to (S)-propane-1,2-diol occurs with overall retention of configuration at phosphorus. This result is consistent with the view that the hydrolysis of substrates by this mutant enzyme proceeds by way of a covalent phosphoenzyme intermediate in the same manner as the wild-type alkaline phosphatase.

Alkaline Phosphatase↗
PubMed1988

Concomitant changes in the acoustic impedance and the cochlear microphonic potentials during twitch contractions of the middle ear muscles in cats.

The effect of twitch contractions of the middle ear muscles in cats on sound transmission through the middle ear (as measured by the cochlear microphonic potential of the inner ear) was compared with the simultaneous changes in the acoustic input impedance of the middle ear at the same frequency. It was found that decreases in impedance were related to an increase in the amplitude of the cochlear microphonics and vice versa. This may imply that decreases in impedance measured during the initial phase of the acoustic reflex in man are true decreases and are not due to transient decoupling of the ossicular chain at any point.

Acoustic Impedance Tests↗