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Biomedical subjects

S Freeman

Publications and source records attributed to S Freeman.

At least 127 records · Page 7Linked to original sources
PubMed1995

Sialoadhesin binds preferentially to cells of the granulocytic lineage.

Sialoadhesin is a macrophage-restricted, sialic acid-dependent receptor of 185 kD that binds to the oligosaccharide sequence NeuAc alpha 2,3Gal on cell surface glycoconjugates. Recent cDNA cloning has shown that sialoadhesin is a new member of the immunoglobulin superfamily with sequence similarity to CD22, a sialic acid-dependent receptor of B lymphocytes. Sialoadhesin has been implicated in cellular interactions of stromal macrophages with developing myeloid cells. In this study, direct evidence for this interaction was obtained in cell-cell binding assays using both native and recombinant forms of the protein. In all assays, sialoadhesin exhibited specific, differential binding to various murine cell populations of hemopoietic origin. In rank order, sialoadhesin bound neutrophils > bone marrow cells = blood leukocytes > lymphocytes > thymocytes. Single-cell analyses confirmed that sialoadhesin selectively bound myeloid cells in complex cell mixtures obtained from the bone marrow and blood. In comparison, a recombinant Fc-chimeric form of murine CD22 showed high binding to B and T lymphocytes, but very low binding to immature and mature myeloid cells. These results are consistent with the notion that sialoadhesin in involved in interactions with granulocytes at different stages of their life histories.

Animals↗
PubMed1995

Retrospective dynamic transmit focusing.

Dynamically-focused on receive, real-time array systems exhibit image degradation far from the focal zone of the fixed transmit lens. A retrospective filtering technique reducing the effects of the fixed transmitter is presented. The filter deconvolves the defocused transmit pattern producing a new in-focus transmit/receive image, where the filter coefficients are derived with a least-squares method. Experimental results are presented for a 128 channel array system showing the method's performance. A proposed architecture for real-time filtering is also discussed.

Equipment Design↗
PubMed1995

Functional development of auditory sensitivity in the fetus and neonate.

The human fetus responds to sound stimuli while still in utero. The rat and cat begin to hear only after birth. Therefore neonatal rat and cat are used as models of the development of auditory sensitivity in the human fetus. The inner ear of rat responds to stimuli delivered directly to it (bone conduction) before the middle ear can conduct sounds to the inner ear. During this period, middle ear development involves mesenchyme resorption, ossicular hardening and opening of the external canal. The latter stages of inner ear development involve increased magnitude of the endocochlear potential which augments cochlear transduction and the active cochlear amplifier. These developmental stages are probably controlled by thyroid hormone which activates several genes leading to the synthesis of proteins and enzymes required for the structural and functional maturation of the ear. This likely includes the Na+,K(+)-ATPase of the stria vascularis which generates the endocochlear potential. The magnitude of the endocochlear potential is dependent on oxygen supply so that the human fetus in utero whose blood carries less oxygen than the newborn has a hypoxia-induced sensorineural hearing loss. Upon birth and transition from placental to pulmonary oxygenation, the oxygen content of blood is increased, the magnitude of the endocochlear potential is elevated and auditory sensitivity is enhanced.

Acoustic Stimulation↗
PubMed1995

Recombination and maternal age-dependent nondisjunction: molecular studies of trisomy 16.

Trisomy 16 is the most common human trisomy, occurring in > or = 1% of all clinically recognized pregnancies. It is thought to be completely dependent on maternal age and thus provides a useful model for studying the association of increasing maternal age and nondisjunction. We have been conducting a study to determine the parent and meiotic stage of origin of trisomy 16 and the possible association of nondisjunction and aberrant recombination. In the present report, we summarize our observations on 62 spontaneous abortions with trisomy 16. All trisomies were maternally derived, and in virtually all the error occurred at meiosis I. In studies of genetic recombination, we observed a highly significant reduction in recombination in the trisomy-generating meioses by comparison with normal female meioses. However, most cases of trisomy 16 had at least one detectable crossover between the nondisjoined chromosomes, indicating that it is reduced--and not absent--recombination that is the important predisposing factor. Additionally, our data indicate an altered distribution of crossing-over in trisomy 16, as we rarely observed crossovers in the proximal long and short arms. Thus, it may be that, at least for trisomy 16, the association between maternal age and trisomy is due to diminished recombination, particularly in the proximal regions of the chromosome.

Chromosome Mapping↗
PubMed1995

Antineoplastic agents 320: synthesis of a practical pancratistatin prodrug.

Owing to its sparingly soluble properties, the potential anticancer drug pancratistatin (1) resisted conventional drug formulation procedures and the synthesis of a water-soluble prodrug became necessary. That important objective for further pre-clinical development was met by devising a route to a disodium phosphate derivative (5). The key step in the synthesis of the phenolic phosphate was phosphorylation of 1,2,3,4-tetraacetoxy-pancratistatin (2) with dibenzyloxy(N,N-diisopropylamido)-phosphine. Subsequent oxidation with m-chloroperbenzoic acid afforded phosphate 4a. Hydrogenolysis of the benzyl esters followed by base-catalysed hydrolysis of the acetate groups led to the water-soluble prodrug 5 in high yield.

Amaryllidaceae Alkaloids↗
PubMed1995

Attention regulation by children with Down syndrome: coordinated joint attention and social referencing looks.

We examined attention regulation of children in two different situations designed to elicit triadic interactions (i.e., between self, other, and object). Thirty-five children with Down syndrome and 23 children with typical development were observed in a semi-structured adult-child interaction designed to elicit coordinated joint attention and an ambiguous situation in which a moving robot prompted an emotional response from the adults in order to elicit social referencing looks from the child. Children with Down syndrome engaged in significantly fewer social referencing looks. Group differences were not found for coordinated joint attention looks, suggesting that the difficulty for children with Down syndrome is in cognitive appraisal abilities.

Adult↗
PubMed1994

Open label study of long-term effectiveness of cisapride in patients with idiopathic gastroparesis.

Cisapride induces acetylcholine release in cells of the myenteric plexus, thus promoting gastrointestinal motility. We studied the effects of cisapride on 11 patients with idiopathic gastroparesis. All had negative gastrointestinal endoscopy, normal glucose, and took no drugs capable of influencing motility. Most (9/11) were prior metoclopramide treatment failures. Patients' symptoms were scored (0-60) for pain, satiety, bloating, nausea, vomiting, and heartburn. All underwent a solid gastric emptying study using a Technetium-99-labeled egg meal and received placebo prior to cisapride. There were 10 females and one male with a mean (+/- SE) age of 37.8 +/- 2.6 years. Disease duration was 7.9 +/- 2.8 years. The dose of cisapride was 30-60 mg/day and the duration of therapy was 12.6 +/- 2.6 months (range 2.5-25 months). The symptom score improved on cisapride from 30.9 +/- 3.6 to 14.4 +/- 2.7 (P < 0.002 signed rank test). Emptying half-time improved from 113 +/- 4 min to 94 +/- 6 min, and 46.9 +/- 2.4% food remaining at 120 min decreased to 35.5 +/- 3.6% (both P < 0.05). Emptying half-time in normals was 68 +/- 5 min with 16.9 +/- 2.9% remaining at 120 min. Nine of 11 patients gained weight, with a mean increase of 6.7 +/- 1.6 lb (range 2-12 lb). We conclude that cisapride significantly reduces gastrointestinal symptoms and promotes weight gain in patients with idiopathic gastroparesis and is associated with improvement in solid gastric emptying. The drug is useful in patients who previously failed metoclopramide.

Adult↗
PubMed1994

Improvement in sensorineural auditory threshold of the guinea-pig fetus following delivery.

The human fetus in utero is hypoxic relative to the neonate due to differences between placental and pulmonary oxygenation. Comparable degrees of hypoxia induced in young and adult animals caused an elevation in hearing threshold of a sensorineural nature. It was hypothesised therefore that the human fetus may also have such an elevation of threshold. This was tested in this study by recording ABR thresholds to bone conducted stimuli in fetal guinea-pigs that were near full term and again in the same animals, after delivery and consequent pulmonary oxygenation. In every animal studied (n = 9), the neonatal threshold was better than that in the fetus. In those fetuses in which a response could be recorded (n = 5), the neonatal threshold was on average 20 dB better than in the fetus. These findings are probably due to a depression of the endocochlear potential induced by the relatively hypoxic state of the fetus. The hypoxic state would lead to a reduced transduction current in the hair cells in response to a stimulus and an elevated hearing threshold. At birth, with the shift to pulmonary oxygenation, the neonate becomes normoxic, the endocochlear potential rapidly reaches near maximal levels and threshold is improved.

Animals↗
PubMed1994

Computerized strain-gauge plethysmography in the diagnosis of symptomatic and asymptomatic venous thrombosis.

This study compares the results of a computerized strain-gauge plethysmograph with ascending lower limb venography in 94 patients with clinical deep venous thrombosis, and in 121 patients with asymptomatic legs being screened after total hip replacement. In the symptomatic patients, strain-gauge plethysmography had a sensitivity of 100%, an accuracy of 73%, a specificity of 64% and a negative predictive value of 100% for thrombosis above the popliteal confluence. In the screened patients, the figures were 38.1%, 55.4%, 60.0% and 81.1% respectively. Computerized strain-gauge plethysmography is a safe, non-invasive, reliable and portable method of excluding proximal thrombosis in a symptomatic patient. It avoids the need for urgent venography when anticoagulation therapy is reserved for those with proximal thrombosis. The device was not valuable as a screening tool after total hip replacement, since it had a low specificity and did not reliably detect the non-occlusive mural femoral thrombi which typically follow this procedure.

Diagnosis, Computer-Assisted↗
PubMed1994

Does single dose salmeterol affect exercise capacity in asthmatic men?

The aim of this study was to investigate whether the long-acting beta-agonist salmeterol affects athletic performance in patients with asthma. The effect of 50 micrograms salmeterol on the cardiorespiratory responses to a progressive maximal cycle exercise test and on endurance capacity (defined as the exercise duration at 70% maximum oxygen uptake), was compared with 200 micrograms salbutamol and a matched placebo in eight asthmatic men. Both salmeterol and salbutamol improved pre- and postexercise forced expiratory volume in one second (FEV1) for maximal and endurance exercise. Following active treatment, patients exercised from a significantly high baseline FEV1, with both salmeterol (3.58(1.16)l) (mean (SD)) and salbutamol (3.55(1.24)l) compared with placebo (3.29(1.35)l). Similar improvements preceded endurance exercise. Cardiorespiratory, haemodynamic or subjective responses to the progressive maximum exercise tests were not different with salmeterol, salbutamol or placebo, nor did endurance capacity change with any treatment modality. Blood lactate levels, after 15 min exercise, were significantly higher with salbutamol (3.64 (1.83) mM), but not with salmeterol (3.03 (1.64) mM), compared with placebo (2.95 (1.69) mM). These results demonstrate the absence of significant cardiorespiratory or metabolic effects during exercise after a single dose of salmeterol, together with a lack-of ergogenic effect, as measured by maximal or endurance exercise performance, in patients with asthma.

Adult↗
PubMed1993

Effects of 1,1-dichloroethene and of some of its metabolites on the functional viability of mouse hepatocytes.

1,1-Dichloroethene (DCE) is hepatotoxic in rodents, and the expression of its toxicity involves probably its metabolism. In this study the role of DCE metabolites in the generation of the hepatotoxic lesion was investigated. Hepatocytes from male BALB/c mice in suspension were used as the experimental model. Cells were incubated with DCE for up to 5 hr and cellular viability was assessed by measurement of the release of lactate dehydrogenase into the medium and by alterations in the reduction of the dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. After incubation for 3 hr DCE at 0.5 mM caused maximal toxicity, whereas at 0.1 mM DCE was only marginally toxic. Cytotoxicity was exacerbated by pretreatment of mice with buthionine sulfoximine (1.6 g/kg), an inhibitor of glutathione biosynthesis, given 4 hr prior to hepatocyte isolation. Inclusion of N-acetylcysteine (10 mM) into the incubate protected cells against DCE-induced cytotoxicity. Coincubation with octylamine (0.5 mM), an inhibitor of cytochrome P450, abolished the cytotoxic potential of 0.5 mM DCE during incubation for 3 hr. DCE toxicity was increased in hepatocytes from mice which had received ethanol or acetone in their drinking water, both of which induce levels of the hepatic cytochrome P450 isozyme P450 2E1. Incubation of cells with the P450 2E1 inhibitors N,N-dimethylformamide (10 mM) or diethyldithiocarbamate (100 microM) protected liver cells against the detrimental effect of DCE. Pretreatment of animals with phenobarbital, which induces the P450 2B subfamily, or 3-methylcholanthrene, which induces P450 1A1, did not affect the degree of hepatocytotoxicity elicited DCE.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Thyroid hormone induces earlier onset of auditory function in neonatal rats.

The effect of thyroid hormone injection on the development of auditory function in neonatal rats was evaluated using auditory nerve-brainstem evoked responses (ABR). The hormone induced earlier onset of auditory function. In order to differentiate between conductive and sensorineural factors, both air-conducted (AC) and bone-conducted (BC) ABR responses were recorded. Neonatal rats were injected with thyroxine (T4), or with saline (control animals), from day of birth (post-natal day-PND-0), daily, until PND 9. AC- and BC-ABRs were recorded from PND 6 up to PND 20. It was found that both AC- and BC-ABR thresholds were lower in the T4-injected rats up to PND 15, after which no difference was found between the two groups. This indicated earlier maturity of both conductive (external and middle ears) and sensorineural (inner ear) factors and is probably due to the earlier appearance in the blood of higher T4 levels, following injection, than that occurring naturally during the neonatal period in these animals.

Animals↗
PubMed1993

Development of hearing in neonatal rats: air and bone conducted ABR thresholds.

While the human full-term neonate can hear at birth, in the rat the onset of auditory function as monitored by recording auditory nerve-brainstem evoked responses (ABR) has been reported to begin on post-natal day (PND) 12-14 and reaches adult thresholds at about 22 days. In order to determine the factors involved in this late onset and then rapid threshold improvement in rats, the ABR to both air conducted (AC) and bone-conducted (BC) auditory stimulation was determined in neonatal rats. ABR to maximal intensity BC stimuli (55 dB above adult rat ABR threshold--55 dB HL*) could be recorded from PND 7-8 while AC responses to 80 dB HL* stimuli, only from PND 11. The air-bone gap (a measure of conductive immaturities only) disappeared on PND 15. This shows that there are both conductive (external and middle ear--Air-bone gap) and sensori-neural (inner ear--BC threshold) immaturities in the neonatal rat; the conductive factors are resolved by PND 15 while the sensori-neural continue after that. With respect to conductive factors, it seems that the state of the ear canal is not important while the chief conductive factors involved probably include mesenchyme resorption and/or ossicular ossification. The chief sensori-neural factor may be the development of the endocochlear potential. It is likely that the human fetus in-utero undergoes similar stages of development.

Acoustic Stimulation↗
PubMed1993

Prognosis of occupational contact dermatitis in New South Wales, Australia.

570 patients with occupational contact dermatitis (OCD) were seen between 1984 and 1990 at the Skin and Cancer Foundation in Sydney. 336 (59%) were followed up 1 to 5 years later. Roughly 1/3 were healed, 1/3 were improved without complete healing, 1/4 had no change and 1/12 of the patients had deteriorated. The overall improvement rate was in excess of 70%. Data derived from these patients demonstrated that changing the work duties of patients with OCD improved their outcome (p < 0.01), whilst leaving the industry altogether resulted in a greater overall healing rate (p < 0.01). No difference existed between the outcome of irritant contact dermatitis compared with allergic contact dermatitis. Atopics as expected had a worse prognosis. The outcome in the construction industry was significantly poorer than other industries. Patients suffering from allergic contact dermatitis from chromate also had a dismal prognosis.

Dermatitis, Contact↗
PubMed1993

Metabolism in the globus pallidus after fetal implants in rats with nigral lesions.

The effect of fetal mesencephalic implants on glucose utilization in selected brain structures and on apomorphine-induced rotational behavior was measured in rats with a unilateral lesion of the substantia nigra. Ipsilateral, but not contralateral, implants decreased the rotational behavior induced by apomorphine. In addition, the nigral lesion decreased glucose utilization in the dorso- and ventrolateral quadrants of the striatum and in the entopeduncular nucleus but increased glucose utilization in the ipsilateral globus pallidus and lateral habenula. The increased metabolism in the globus pallidus was attenuated by ipsilateral, but not contralateral, mesencephalic implants which also decreased glucose utilization in the dorsomedial caudate nucleus. These results indicate that the ability of an ipsilateral mesencephalic graft to ameliorate the motor behavior in rats with nigral lesions is associated with changes in the functional activity of the ipsilateral globus pallidus.

Analysis of Variance↗