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Biomedical subjects

D Jackson

Publications and source records attributed to D Jackson.

At least 127 records · Page 7Linked to original sources

Stimulation and inhibition of angiogenesis by placental proliferin and proliferin-related protein.

In many mammalian species, the placenta is the site of synthesis of proteins in the prolactin and growth hormone family. Analysis of two such proteins, proliferin (PLF) and proliferin-related protein (PRP), revealed that they are potent regulators of angiogenesis; PLF stimulated and PRP inhibited endothelial cell migration in cell culture and neovascularization in vivo. The mouse placenta secretes an angiogenic activity during the middle of pregnancy that corresponds primarily to PLF, but later in gestation releases a factor that inhibits angiogenesis, which was identified as PRP. Incubation of placental tissue with PLF led to the specific binding of this hormone to capillary endothelial cells. Thus PLF and PRP may regulate the initiation and then the cessation of placental neovascularization.

Animals↗

CD44H expression by human neuroblastoma cells: relation to MYCN amplification and lineage differentiation.

The human CD44 cell surface glycoprotein has been involved in a variety of functions including lymphocyte homing, extracellular cell matrix attachment, and tumor metastasis. Due to the alternative splicing of the single gene, a large family of different variants or isoforms is generated. Several reports have indicated an up-regulation of CD44 variant (v) isoforms in malignant process, conferring metastatic potential to non-metastatic cells. Neuroblastoma is a tumor characterized by an aggressive and metastatic behavior in advanced stages with amplification of the MYCN protooncogene. In this report we show that the CD44 standard molecule is highly expressed in 100% of stage I-III, IVs neuroblastomas and ganglioneuromas but only in a subset of stage IV tumors. In contrast, no expression of CD44 was detected on MYCN amplified stage IV tumors, thus demonstrating a highly significant negative relationship between MYCN amplification and CD44 expression in neuroblastoma. The expression of CD44 on neuroblastoma cultured cell lines was not shown to be related to MYCN amplification but rather linked to the S-type, schwann/glial differentiation lineage. Immunochemical analysis of tumor samples with anti-CD44v3 and -v6 antibodies and Northern blot analysis of mRNA from cell lines with probes spanning exons 4-10 did not reveal any expression of splice variants on neuroblastomas of all stages and cell lines, thus ruling out a major role of these isoforms in neuroblastoma progression and metastasis.

Blotting, Northern↗

Postural tremor of Parkinson's disease.

Previous studies have reported the resting tremor (RT) of Parkinson's disease to occur at frequencies between 3-7 Hz and to be characterised by an alternating pattern of electromyographic (EMG) bursting activity between opposing muscles. A postural tremor (PT), of higher frequency (> 6 Hz) and with a synchronous pattern of EMG activity, has also been previously described in Parkinson's disease. We investigated the electrophysiological and pharmacological properties of both the RT and PT of 11 patients with Parkinson's disease and 10 patients with essential tremor in a double-blind, placebo-controlled study of L-Dopa/benserazide and propranolol. Tremor amplitude and frequency were assessed via bidirectional accelerometry, and the pattern of activation of the antagonist muscles of the forearm was determined with use of surface EMG. In the Parkinson's disease group studied, the frequency, EMG pattern of bursts, and response to L-Dopa were similar for the two tremors (median improvement of RT by 70% and PT by 61%). Despite some overlap between the Parkinson's disease and essential tremor groups in the electrophysiology of the tremor, there was no such dramatic pharmacological response in the latter group. These results suggest that the RT and PT of Parkinson's disease share a common pathophysiology and are distinct from essential tremor.

Adult↗

Novel features of the respiratory tract T-cell response to influenza virus infection: lung T cells increase expression of gamma interferon mRNA in vivo and maintain high levels of mRNA expression for interleukin-5 (IL-5) and IL-10.

Analysis of the respiratory tract before and after primary influenza virus infection revealed a virus-induced preferential accumulation of a CD8+ T-cell population that coexpresses mRNA for interleukin-5 (IL-5) and IL-10 with virus dose-dependent high levels of gamma interferon. However, cytokine production in lung tissues was not restricted to the T-cell population, since CD3- cells were found to express mRNA for various cytokines, including IL-4 and particularly IL-6 and granulocyte-macrophage colony-stimulating factor. These data provide in vivo evidence for a local respiratory tract immune response to influenza virus infection dominated by cytokine-producing CD8+ T cells.

Animals↗

Identifying true lidocaine allergy.

Allergies to local anesthetics are rare. More often, the allergic response is caused by a metabolite, preservative or unrelated substance. At times, an apparent allergic reaction can be brought on by anxiety. An idiopathic reaction to lidocaine is described, and allergy testing is discussed.

Anesthesia, Dental↗

EEG and prognosis of neurologic recovery of dogs under profound hypothermic circulatory arrest.

Deep hypothermia (18-20 degrees C) (DH) during prolonged circulatory arrest and cardiopulmonary bypass is used to repair complex intracardiac lesions and vascular neurosurgical lesions. DH diminishes the risk of ischemic damage and multiorgan failure after circulatory arrest. Profound hypothermia (PH) to 6-7 degrees C has recently been reported to improve the neurological outcome of dogs after 2 h of circulatory arrest. There are no reports of the possible utility of EEG activity to predict the neurological outcome. As a part of a controlled study of cardiopulmonary bypass and 2 h of circulatory arrest we compared EEG recovery to the neurological outcome in 2 groups of dogs: 4 under DH and 4 under PH. All of the dogs under PH had a good outcome: mean neurodeficit score was 6.25/500 in PH and 139.25/500 in DH dogs (P < 0.03); mean histopathological score was 19.25/100 for DH and 47.75/100 in PH dogs (P < 0.03). EEG activity 2 h after reperfusion and starting of rewarming correlated with eventual neurological outcome. EEG variables associated with good outcome were: main final frequency and degree of rhythmicity of the activity. We conclude that PH exerted a protective effect for animals undergoing 2 h of circulatory arrest. EEG was a useful tool for predicting neurological outcome under the studied conditions.

Animals↗

Functional significance of the mu rhythm of human cortex: an electrophysiologic study with subdural electrodes.

The existence of the mu rhythm and its general anatomical and physiological relationships are well known. There are few data, however, regarding the details of its anatomical and physiological specificity. We implanted fronto-temporal subdural electrode grids in 9 patients with intractable epilepsy to facilitate their surgical management. A 7-11 Hz cortical mu rhythm was observed in 5-16 electrodes located over the sensorimotor cortex as mapped by electrical stimulation. The mu rhythm was blocked by contralateral face and arm movements, passive movements of contralateral arm, and by ipsilateral arm movements. There was correspondence between the body area movement of which blocked the mu at a given site and the body region that was affected by stimulation at the same site. Power spectral analysis showed an overall decrease in power in all frequency bands. This was less prominent in the 14-100 Hz band resulting in a relative increase in high frequency power in association with movement. We conclude that both the presence and blocking of mu rhythm are specific to the somatic representation of the cortex from which it is recorded. Its functional significance may be similar to other sensory rhythms like the occipital alpha rhythm.

Adolescent↗

Developmental consequences of diet and activity.

The effect of a protein-deficient and a protein-surfeit diet and continuous access to an activity wheel on food intake, growth, and body temperatures of behaviorally thermoregulating White Leghorn chicks was assessed in two experiments. In Experiment 1, both imbalanced-protein diets depressed intake and growth and differentially affected activity relative to a control diet, but activity did not ameliorate the deleterious effect of a high-protein diet on growth. Diet groups with continuous access to a running wheel did not differ on any measure from corresponding inactive dietary control groups. In Experiment 2, these results were replicated in a lower ambient temperature, and an effect of diet on body temperature emerged. Diets that affected spontaneous activity or body temperature also affected death feigning, a predation defense behavior. The data from behaviorally thermoregulating chicks are consistent with previous findings that activity does not depress growth rate in animals who cannot convert a portion of their intake into adipose tissue.

Animals↗

Immune response of human volunteers and animals to vaccination with egg-grown influenza A (H1N1) virus is influenced by three amino acid substitutions in the haemagglutinin molecule.

Inactivated subunit vaccines were prepared from high-growth reassortants derived from two separate egg isolates from a single clinical specimen of influenza A (H1N1) virus. One of these reassortants, NIB-14, was antigenically indistinguishable from isolates made in tissue culture, while the other, NIB-17, was antigenically different and typical of egg isolates. The viruses differed by three amino acid residues in the haemagglutinin (HA) molecule and the anti-HA serological response induced was studied in animal models and human volunteers. In the volunteer groups both vaccines induced very high levels of circulating haemagglutination inhibition antibodies but with different serological specificities. Both NIB-14 and NIB-17 vaccines induced high levels of cross-reactive antibodies capable of reacting with both strains, but only NIB-14 vaccine induced significant levels of strain-specific antibodies capable of reacting exclusively with the homologous strain. Antisera containing only cross-reactive antibodies proved as capable of virus neutralization as antisera containing high levels of strain-specific antibodies. We extended the argument that epidemic strains are antigenically more closely related to tissue culture isolates and established that viruses which differ by only single amino acids at critical points in the HA structure can induce a significantly different immune response when used as inactivated vaccines.

Adolescent↗

Transposon-induced inversion in Antirrhinum modifies nivea gene expression to give a novel flower color pattern under the control of cycloidearadialis.

The nivea (niv) gene of Antirrhinum majus encodes chalcone synthase, an enzyme involved in synthesis of anthocyanin pigments. The nivrec:98 allele contains a single copy of the transposon Tam3 inserted at the niv locus. A large chromosomal rearrangement derived from this mutant has been shown to be flanked by two copies of Tam3. In this study, we compared sequences involved in this rearrangement with their progenitor sequences and concluded that the rearrangement is an inversion resulting from an aberrant transposition occurring shortly after replication of Tam3 that left both copies of Tam3 active after the rearrangement. Excision of Tam3 from its position adjacent to the niv coding region resulted in a novel distribution of anthocyanin pigment in the flower tube, caused by the interaction of the new sequences with the remnant of the niv promoter. The new sequences upstream of niv serve both to enhance niv transcription and to redirect the pattern of gene expression, placing niv under the control of the gene cycloidearadialis, which determines the morphogenetic polarity of the flower.

Alleles↗

Cell proliferation in the liver and thyroid of C57Bl/10J mice after dietary administration of chlordane.

Chlordane is a polychlorinated hydrocarbon that causes liver enlargement and induces mixed-function oxidases similar to those induced by phenobarbitone in the mouse. We have assessed the hepatocarcinogenicity (after 2 years) and the time course (over 6 months) of liver and thyroid cell proliferation in C57Bl/10J mice exposed to chlordane at 50 ppm in the diet, using the same batch of food for both carcinogenicity and cell proliferation studies. In the bioassay, 15/39 survivors had hepatocellular adenomas and a further 5/59 had carcinomas, compared with less than 5% incidence of primary hepatic tumors in concurrent controls. Among unscheduled deaths, 1/40 adenomas and 2/40 carcinomas were recorded. There were no macroscopically observed thyroid lesions. In the proliferation study, mice were killed on days 4, 5, 8, 15, 29, 99, and 190 after the start of dosing. Withdrawal groups were included from days 29 to 99 and from days 190 to 247. Replicating cells were labeled via bromodeoxyuridine delivered by osmotic minipump for 3 days before necropsy. In the thyroid, the peak labeling index (LI) was seen on day 5 (LI = 5.99 +/- 2.90% versus 1.00 +/- 20% in controls), while in the liver the peak was on day 8 (9.0 +/- 1.6% versus 0.5 +/- 0.4% in controls). Both organs had an elevated LI for the first month of dosing, but while the thyroid follicular LI was similar to control at 99 and 190 days, the liver LI was significantly elevated at all time points except in the withdrawal groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Liver Cell↗

Nursing frequency and the energy intake from breast milk and supplementary food in a rural Thai population: a longitudinal study.

A group of 60 infants representative of a rural Thai population were studied longitudinally over the first year of life. Their breast milk intake, supplementary food intake and nursing patterns were measured for 2 consecutive days at about 15, 45, 90, 180, 270 and 360 days of age. For the sample as a whole, the estimated peak value for energy intake from breast milk was 529 kcal (2213 kJ) and occurred at 34 days post-partum. Thereafter milk intake declined, with 40% of infants fully weaned by the end of the first year. Supplements were introduced early, with 15% of infants supplemented by 2 weeks and 68% by 6 weeks. Higher levels of supplementation were associated with lower breast milk intake. In addition there was an independent positive effect of nursing patterns (number of breast feeds per day). Interaction terms show that both supplementary feeding and number of feeds have quantitatively different effects at different ages: breast milk intake varies more with level of supplementation in younger infants than in older infants, and varies more with number of feeds in older infants than in younger infants. Higher peak levels of breast milk intake were followed by a steeper decline, and infants who took more breast milk at 15 days were more likely to be fully weaned by their first birthday.

Age Factors↗

Impact of L-dopa on striatal acetylcholine release: effects of 6-hydroxydopamine.

We investigated the effects of the dopamine (DA) precursor L-dihydroxyphenylalanine (L-DOPA) on electrically evoked acetylcholine (ACh) overflow from rat striatal slices. Some animals were pretreated 1 to 2 months earlier with 6-hydroxydopamine, (6-OHDA), a catecholamine neurotoxin, so as to selectively destroy DA terminals (98.6% striatal DA depletion). Although the addition of L-DOPA (10 microM) produced a 37% inhibition of ACh overflow in slices from lesioned rats, it failed to affect ACh overflow in slices from intact animals. In contrast, ACh overflow from intact slices exposed to L-DOPA and to the DA uptake inhibitor nomifensine (1 microM) was 22% greater than in the presence of nomifensine without L-DOPA. ACh overflow from slices prepared from lesioned rats was 45% greater with both drugs than in the presence of nomifensine by itself. Superfusion with the aromatic L-amino acid decarboxylase (AADC) inhibitor NSD-1055 (250 microM) abolished the inhibitory effects of L-DOPA, as did L-sulpiride (1 microM), an inhibitor of DA receptors of the D2 subtype. These results suggest that inhibition of ACh overflow by L-DOPA is mediated by DA formed from exogenous L-DOPA which then acts on D2 receptors. They further indicate that the net impact of the loss of nigrostriatal terminals is an increased dopaminergic inhibition of striatal cholinergic interneurons in response to exogenous L-DOPA. This appears to result in large part from a lesion-induced reduction in high-affinity reuptake of DA formed from exogenous L-DOPA.

3,4-Dihydroxyphenylacetic Acid↗

The immunopharmacological actions of nedocromil sodium relative to the use of its 2% ophthalmic solution.

The immunopharmacological actions of nedocromil sodium are fully compatible with administration to man. Nedocromil sodium exhibits a wide range of anti-inflammatory actions. When compared with sodium cromoglycate, nedocromil sodium is more potent and a major difference is seen in the Ascaris-sensitised monkey subjected to bronchial challenge with specific antigen. In this model of chronic airway disease nedocromil sodium provides significant protection against changes in airway resistance and lung compliance provoked by antigen challenge. Sodium cromoglycate does not. This difference is most readily explicable by the greatly enhanced effect of nedocromil sodium, relative to that of sodium cromoglycate, in preventing the release of mediators such as histamine, leukotriene C4 and prostaglandin D2 from the cellular population of the chronically inflamed bronchus, especially from mast cells of the mucosal type. There is growing evidence that these mediators are important in allergic diseases of the eye and this additional activity may be expected to give nedocromil sodium extended scope in the management of conjunctivitis in which allergic inflammation and hyperresponsiveness are significant pathophysiological factors.

Animals↗

CD24, a signal-transducing molecule expressed on human B cells, is a major surface antigen on small cell lung carcinomas.

Cell lines derived from human small cell carcinoma of the lung express high levels of a surface polypeptide termed the cluster-w4 antigen, which was previously identified as a potential target for toxin-based immunotherapy of lung cancer. We have cloned a complementary DNA encoding the cluster-w4 antigen from COS-1 fibroblasts transfected with a SW2 small cell carcinoma library, by panning with a mixture of the cluster-w4-specific monoclonal antibodies SWA11, SWA21, and SWA22. The sequence of the cluster-w4 complementary DNA encodes an unusually short (80-amino acid) protein identical to that recently reported for the leukocyte activation molecule CD24 except for a single valine-alanine substitution due to a single-base polymorphism within the region of the gene coding for the extracellular domain. Biochemical analyses of the cloned cluster-w4 antigen confirmed both the presence of the phosphatidylinositol tail and the extensive glycosylation reported for the CD24 molecule. Furthermore, the cloned cluster-w4 antigen expressed on COS cells was shown to react with a comprehensive panel of CD24-specific monoclonal antibodies, as assessed by indirect immunofluorescence staining. Northern blot hybridization indicated the presence of several transcript sizes for the cluster-w4 antigen that were greatly overexpressed in small cell carcinoma cell lines, compared with normal hemopoietic cells and CD24-positive cell lines. Southern blot hybridization of restriction digests of genomic DNA identified a complex pattern of bands consistent with either a complex gene structure containing many exons or the presence of a family of closely related genes.

Alanine↗

Inverted repeat structure of the Sry locus in mice.

The testis-determining gene Sry is located on the short arm of the mouse Y chromosome in a region known to have undergone duplications and rearrangements in comparison with the equivalent portion of the human Y chromosome. Detailed analysis of the Sry genomic locus reveals a further difference in that the mouse Sry open reading frame lies within 2.8 kilobases of unique sequence at the center of a large inverted repeat. This repeat, which is found in both Mus musculus musculus and Mus musculus domesticus Y chromosomes, is not present at the human SRY locus. Recombination involving the repeat region may have led to an 11-kilobase deletion, precisely excising Sry in a line of XY female mice.

Animals↗

Solution structures of nisin A and its two major degradation products determined by n.m.r.

The conformations of nisin and two major degradation products, nisin-(1-32)-peptide (nisin1-32) and des-delta Ala5-nisin1-32 (where delta Ala is alpha beta-didehydroalanine), in aqueous solution have been determined from n.m.r. data. Sequential assignments of the peptides using correlation spectroscopy ('COSY'), homonuclear Hartmann-Hahn spectroscopy ('HOHAHA'), nuclear Overhauser enhancement spectroscopy (NOESY), relayed NOESY and rotating-frame nuclear Overhauser spectroscopy (ROESY) experiments are presented, including stereospecific assignments of beta-methylene protons of the lanthionine residues. ROESY experiments are also used to detect flexible regions in the polypeptide chain. A dynamic-stimulated-annealing approach is used for structural determination. It can be concluded that all these peptides are flexible in aqueous solution, with no experimental evidence of preferred overall conformations; the only defined conformational features are imposed by the presence of the lanthionine residues. Low-temperature studies also reveal that des-delta Ala5-nisin1-32 adopts conformations similar to those when the ring is intact, suggesting that the loss of activity of this degradation product is due to the absence of the delta Ala5 residue rather than to the conformational consequences of ring-opening.

Amino Acid Sequence↗