Search PubMed⌕ Search

Biomedical subjects

D Price

Publications and source records attributed to D Price.

At least 19 recordsLinked to original sources
PubMed1995

The MATK tyrosine kinase interacts in a specific and SH2-dependent manner with c-Kit.

We have cloned a protein tyrosine kinase, MATK, which is expressed abundantly in megakaryocytes and the brain. We investigated whether MATK participates in the c-Kit ligand/stem cell factor (KL/SCF) signaling pathway in the megakaryocytic cell line CMK. After KL/SCF stimulation, five major proteins of molecular masses of 145, 113, 92, 76, and 63 kDa were rapidly and transiently tyrosine-phosphorylated in a time-dependent manner, peaking within 5 min, and returning to basal levels within 60 min. To study the role of MATK in the KL/SCF signaling pathway, glutathione S-transferase (GST) fusion proteins containing SH2 and SH3 domains of MATK were cloned, expressed in Escherichia coli, and purified. MATK-SH2, but not MATK-SH3, precipitated the tyrosine-phosphorylated c-Kit (molecular mass of 145 kDa) in KL/SCF-stimulated CMK cells. Other GST fusion proteins containing the SH2 domain of p85 of phosphatidylinositol 3-kinase, phospholipase C gamma-1, and ras-GAP also precipitated c-Kit. The tyrosine-phosphorylated c-Kit was co-immunoprecipitated with anti-MATK and anti-p85 antibodies in KL/SCF-stimulated CMK cells, but not in granulocyte-macrophage colony stimulating factor or interleukin-6-stimulated cells, suggesting receptor specificity. These results indicate that MATK associates with the c-Kit receptor following specific stimulation by KL/SCF via its SH2 domain and likely participates in transduction of growth signals induced by this cytokine in megakaryocytes.

GTPase-Activating Proteins↗
PubMed1995

Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins.

Transgenic FVB/N mice overexpressing human (Hu) or mouse (Mo) Alzheimer amyloid precursor protein (APP695) die early and develop a CNS disorder that includes neophobia and impaired spatial alternation, with diminished glucose utilization and astrogliosis mainly in the cerebrum. Age at onset of neophobia and age at death decrease with increasing levels of brain APP. HuAPP transgenes induce death much earlier than MoAPP transgenes expressed at similar levels. No extracellular amyloid was detected, indicating that some deleterious processes related to APP overexpression are dissociated from formation of amyloid. A similar clinical syndrome occurs spontaneously in approximately 20% of nontransgenic mice when they reach mid- to late-adult life, suggesting that APP overexpression may accelerate a naturally occurring age-related CNS disorder in FVB/N mice.

Aging↗
PubMed1994

Short AV interval VDD pacing does not prevent tilt induced vasovagal syncope in patients with cardioinhibitory vasovagal syndrome.

Eleven subjects (mean age 50 years, range 33-71 years), who had previously received permanent dual chamber pacemakers for cardioinhibitory vasovagal syncope, underwent paired Westminster protocol tilt tests, one with short AV delay VDD pacing and one without pacing, to test the hypothesis that continuous ventricular pacing would prevent the cardiac initiation of vasovagal syncope. Nine (82%) of the paced tilts produced positive vasovagal outcomes compared with seven (64%) of the unpaced tilts. No important differences in the heart rate or blood pressure behavior during tilt or the time to positive vasovagal outcomes were observed between the paired tilts. There was more accelerated syncope/presyncope once symptoms had developed during the paced tilts of subjects in whom both study tilts were positive, although this did not reach statistical significance (P = 0.054). This study shows that atrial synchronous ventricular pacing does not prevent the initiation, or progression, of tilt induced vasovagal syncope in predisposed subjects.

Adult↗
PubMed1992

Interferon modulation of 5-fluorouracil: use in neoadjuvant therapy inhibits experimental liver metastases in nude mice.

Experimental liver metastasis was studied in 4-5 week old athymic nude mice that were injected intrasplenically with a human colorectal tumor cell line (LoVo). A treatment schedule combining 5-fluorouracil and interferon (IFN) was previously shown to inhibit liver metastases. When this treatment was delayed until after splenectomy at 1, 2 and 3 weeks after tumor cell injections, liver metastases were not inhibited. However, when IFN was given during the interval between tumor cell injections and splenectomy (as neoadjuvant therapy), liver metastases were inhibited in the 2 and 3 week groups, but not in the 1 week group.

Animals↗
PubMed1991

Tonic and phasic orientation in full-term and preterm infants.

Thirty-three full-term infants and thirty-eight preterm infants (on average born at 30 weeks gestation) were tested for their latency to turn toward checkered stimulus patterns (phasic orienting or "attention-getting") and for the duration of their initial fixation (tonic orienting or "attention-holding"). Plotted against the logarithm of the subjects' postconceptional age, turning latency fell linearly between 36 and 120 weeks, while fixation time fell abruptly at 53 weeks. Preterm and full-term infants showed the same developmental trends, implying that both of these attentional behaviors are biologically timetabled and that neither is greatly affected by premature extrauterine experience. Unexpectedly, phasic orientation in the first 30 postnatal days was significantly faster in preterm than in full-term infants, and fixation times failed to differ. Despite the necessary functional integration of phasic and tonic orienting in mature visual scanning and attention, the present results suggest an independence in their early postnatal development and that neither is mature at birth.

Arousal↗
PubMed1991

Tumour localisation with a radioactively labelled reshaped human monoclonal antibody.

A genetically reshaped human IgG1 monoclonal antibody (Hu2PLAP) with anti-tumour specificity, was radiolabelled with Indium-111 by chelation with a new macrocyclic compound (DOTA) which allows the production of stable radioimmunoconjugates for in vivo application. This was used to image seven patients with malignant disease, of whom two had been previously exposed to mouse monoclonal antibodies and had developed human anti-mouse antibodies (HAMA). Successful tumour localisation was seen in the four patients with active disease and antigen positive tumours. No patient showed any antibody responses against Hu2PLAP, but three out of six patients tested showed an immune response against the macrocycle DOTA. Reshaped human monoclonal antibodies with anti-tumour specificity may facilitate repeated administrations of radioactive antibodies, thus allowing new possibilities, both in the diagnosis and treatment of cancer.

Adult↗
PubMed1990

The Rett syndrome: progress report on studies at the Kennedy Institute.

Clinical, biochemical and pathological studies in patients with the Rett syndrome (RS) are presented. The neuropathological changes and alterations in neurotransmitter markers are particularly interesting and provide valuable information that may be helpful in understanding the behavior and neurological phenotype of RS.

Adolescent↗
PubMed1990

Release of peptide cotransmitters from a cholinergic motor neuron under physiological conditions.

In previous studies, we demonstrated that B15, one of the two cholinergic motor neurons of the accessory radula closer muscle of Aplysia, synthesizes two peptides, small cardioactive peptides A and B (SCPA and SCPB), that, when exogenously applied, increase the size and relaxation rate of muscle contractions elicited by motor neuron stimulation. In the present experiments, we obtained evidence that the SCPs are released under physiological conditions. Specifically, we characterized firing patterns of motor neuron B15 during normal behavior, simulated them in vitro, and demonstrated that this type of neuronal activity produces decreases in SCP levels in neuronal processes and terminals. We also obtained evidence that suggests that enough SCP is released under physiological conditions to modulate neuromuscular activity in the accessory radula closer. We demonstrated that physiological activity of neuron B15 produces significant increases in muscle cAMP levels. Furthermore, increases in the size and relaxation rate of muscle contractions can be produced by changes in stimulation parameters that are also likely to maximize effects of released endogenous SCPA and SCPB.

Animals↗
PubMed1990

Epidemiology of shingles.

One thousand and nineteen patients with acute varicella zoster viral infection were referred to the physiotherapy department for treatment between 1978 and 1986. Sixty per cent were women and 40% were men with a mean age of 58 years (range 9-96 years). The prevalence varied between 1.3 and 1.6 per 1000 per annum. The left side was affected in 52% while the right was affected in 48%. The thoracic dermatomes were the most commonly affected (56%) followed by cervical (17%), lumbar (10%), sacral (5%), and the trigeminal nerve was infected in 12%. There was a significant seasonal (P less than 0.001) variation in the prevalence of acute varicella zoster virus infection, most common in the summer and least common in the spring. There was no clustering in time and space so that it is unlikely that the varicella zoster virus is infective or that re-exposure to the virus causes reactivation of the latent virus.

Adolescent↗
PubMed1989

Neuropathological changes in early HIV-1 dementia.

Early pathological abnormalities in human immunodeficiency virus (HIV-1)-related dementia have not been well documented. We report a homosexual man with fatigue and intermittent diarrhea in whom early HIV-1-related dementia was demonstrated during neurological screening in the Multicenter AIDS Cohort Study. Within 4 months he died of massive epistaxis, and the brain revealed astrocytosis of white matter and mild pallor of myelin staining in the absence of inflammation, multinucleated giant cells, and brain atrophy.

AIDS Dementia Complex↗
PubMed1989

Diagnosis and incidence of cardiac injury in children with blunt thoracic trauma.

Over a 20-month period, we prospectively studied 41 children with blunt thoracic trauma (BTT) to determine the incidence and morbidity of cardiac injury in this population. Four patients died, and the data were incomplete in 10, leaving 27 for analysis. Serial electrocardiograms (ECG) were abnormal in 36% of the patients studied, serial creatine phosphokinase isoenzyme (CK-MB) ratios were elevated in 31%, echocardiogram showed septal dysfunction in 14%, and pyrophosphate scan showed grade 1 uptake in 14%. There was poor correlation among tests, since only four patients had more than one abnormal test. There was no significant difference in Injury Severity Score or Thoracic Abbreviated Injury Scale between patients with and without abnormal investigations. No patient in the study developed arrhythmias or cardiac failure. In 13 trauma-related deaths undergoing autopsy over the same period, including the four with thoracic trauma, none had evidence of cardiac injury. These results indicate a striking lack of consistency in the diagnosis of posttraumatic cardiac injury in children using standard investigations. The absence of adverse cardiac events in surviving patients and the lack of autopsy evidence of cardiac injury in the trauma deaths suggest that the actual incidence and clinical significance of these lesions in children is lower than generally reported. Children with BTT should be followed clinically, and reliance on screening tests should be avoided.

Adolescent↗
PubMed1989

Ergometrine and 5-hydroxytryptamine binding sites in rat brain and myometrium.

Functional studies suggest that ergometrine is a partial agonist involving 5-hydroxytryptamine (5-HT) receptors in rat uterus. Ergometrine displaced [3H]5-HT from specific binding sites in rat brain, but did not displace [3H]5-HT at functionally important concentrations in rat myometrium. These binding studies indicate that the agonist and antagonist actions of ergometrine in rat uterus arise from its initial interaction with binding sites other than those for 5-HT.

Animals↗
PubMed1988

Serotonin 5-HT1D receptors in human prefrontal cortex and caudate: interaction with a GTP binding protein.

Radioligand binding studies were performed to characterize serotonin 5-HT1D receptors in postmortem human prefrontal cortex and caudate homogenates. [3H]5-HT binding, in the presence of pindolol (to block 5-HT1A and 5-HT1B receptors) and mesulergine (to block 5-HT1C receptors), was specific, saturable, reversible, and of high affinity. Scatchard analyses of [3H]5-HT-labeled 5-HT1D sites in human prefrontal cortex produced a KD value of 4.2 nM and Bmax of 126 fmol/mg protein. In competition experiments, 8-hydroxydipropylaminotetralin, trifluoromethylphenylpiperazine, mesulergine, 4-bromo-2,5-dimethoxyphenylisopropylamine, and ICS 205-930 had low affinity for [3H]5-HT-labeled 5-HT1D sites, indicating that the pharmacology of the 5-HT1D site is distinct from that of previously identified 5-HT1A, 5-HT1B, 5-HT1C, 5-HT2, and 5-HT3 sites. 5-HT1D sites in human brain have a similar pharmacology to the 5-HT1D sites previously identified in rat, porcine and bovine brains. Guanyl nucleotides, guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) and guanosine 5'-(beta, gamma-imido)-triphosphate (Gpp(NH)p), modulated the binding of [3H]5-HT to 5-HT1D sites, whereas adenyl nucleotides had no effect. These findings are supportive of the presence of serotonin 5-HT1D receptors in human prefrontal cortex and caudate which appear to be coupled to a GTP binding protein.

Adenine Nucleotides↗
PubMed1988

Incidence and persistence of Pseudomonas aeruginosa in whirlpools.

Pseudomonas aeruginosa was isolated from seven commercial and two residential whirlpools that were treated with halogens. None of the commercial whirlpools was constantly maintained at appropriate disinfection levels. Superchlorination or the draining, cleaning, disinfection, and refilling of whirlpools markedly reduced densities of P. aeruginosa in whirlpool water, but the bacterial populations were rapidly reestablished (less than 10(3) cells per ml) when disinfectant concentrations decreased below recommended levels (chlorine, 3.0 ppm [3.0 micrograms/ml]; bromine, 6.0 ppm). P. aeruginosa in the water was replenished from various sources, such as hoses used to fill the whirlpool and the biofilm in the filter and piping of the whirlpool systems. Daily monitoring and adjustment of chemical characteristics (regardless of bather load) were essential for controlling densities of P. aeruginosa.

Bromine↗