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P Thompson

Publications and source records attributed to P Thompson.

At least 91 records · Page 5Linked to original sources
PubMed1998

The human homolog of HAVcr-1 codes for a hepatitis A virus cellular receptor.

The hepatitis A virus cellular receptor 1 (HAVcr-1) cDNA was isolated from a cDNA expression library of African green monkey kidney (AGMK) cells by using protective monoclonal antibody (MAb) 190/4, which blocks the binding of hepatitis A virus (HAV) to AGMK cells. The HAVcr-1 cDNA codes for havcr-1, a 451-amino-acid class I integral-membrane mucin-like glycoprotein of unknown natural function. To determine the existence of a human homolog(s) of HAVcr-1 (huHAVcr-1), we used HAVcr-1-specific primers to amplify cDNAs from human liver and kidney mRNA by reverse transcription-PCR. Nucleotide sequence analysis revealed that the amplified liver and kidney huHAVcr-1 cDNAs were identical and that they coded for a 359-amino-acid glycoprotein, termed huhavcr-1, which was approximately 79% identical to havcr-1. The six Cys residues of the extracellular domain of havcr-1 and its first N-glycosylation site were conserved in huhavcr-1. However, the number of hexameric repeats of the mucin-like region was reduced from 27 in havcr-1 to 13 in huhavcr-1. In addition, 12 C-terminal amino acids in the cytoplasmic domain of huhavcr-1 were deleted. Northern blot analysis of poly(A) RNA showed that huhavcr-1 is expressed in every organ analyzed, including the liver, small intestine, colon, and spleen, and that it is expressed at higher levels in the kidney and testis. Although dog cells transfected with the huHAVcr-1 cDNA did not express the protective 190/4 epitope, they bound hepatitis A virus (HAV) and gained limited susceptibility to HAV infection. Treatment with MAb 190/4 did not protect AGMK cell transfectants expressing huhavcr-1 against HAV, suggesting that HAV infected these cells via the huhavcr-1 receptor and not the endogenously expressed havcr-1, which was blocked by MAb 190/4. Our data demonstrate that huhavcr-1 is a binding receptor for HAV and suggest that it is also a functional receptor for HAV.

Amino Acid Sequence↗
PubMed1998

Clozapine therapy for older veterans.

OBJECTIVE: The effectiveness of clozapine treatment in a treatment-refractory sample of older adult veterans with primary psychosis was examined. METHODS: Data were collected over a five-year period for patients age 55 and older who were given clozapine because of a history of treatment-refractory or treatment-intolerant psychosis. At initiation of clozapine therapy, baseline demographic, clinical, and psychopathology data were collected. At baseline and quarterly, patients' psychopathology was rated with the Brief Psychiatric Rating Scale (BPRS), and involuntary movements were rated with the Abnormal Involuntary Movement Scale (AIMS). RESULTS: The 329 patients age 55 or older who received clozapine during the study period represented 10 percent of all patients on clozapine therapy in the VA system. Of the 312 patients for whom demographic information was available, 294 were men and 18 were women. Overall, patients improved on clozapine therapy, although wide variation in drug response was observed. Complete BPRS and AIMS data were available for 97 patients. The 55- to 64-year-old group had a mean improvement in total BPRS score of 19.8 percent, with 42.6 percent showing more than a 20 percent improvement; those age 65 and older had a mean improvement of 5.7 percent, with 17.2 percent showing an improvement greater than 20 percent. The 97 patients with complete AIMS data showed a mean improvement of 16.6 percent in total score. CONCLUSIONS: Clozapine is an important therapeutic agent for older adults with treatment-refractory psychosis. Patients between the ages of 55 and 64 may have a better response than those age 65 and older.

Adult↗
PubMed1998

Adolescents from families of divorce: vulnerability to physiological and psychological disturbances.

Multiple factors contribute to the vulnerability of adolescents to physiological and psychological disturbances following parental divorce. These include father absence, interparental conflict, economic distress, multiple life stressors, parent adjustment, and short-term crisis. Clinical and societal problems manifested in these vulnerable adolescents are discussed. Systems theory is used to explain this vulnerability of adolescents and to identify appropriate interventions and policies to promote health in this population. Policies recommended include required divorce mediation, early referrals for family and sibling therapy, and school programs to identify and support those most vulnerable.

Adaptation, Psychological↗
PubMed1997

Homozygous inactivation of the NF1 gene in bone marrow cells from children with neurofibromatosis type 1 and malignant myeloid disorders.

BACKGROUND: The risk of malignant myeloid disorders in young children with neurofibromatosis type 1 is 200 to 500 times the normal risk. The gene for neurofibromatosis type 1 (NF1) encodes neurofibromin, a protein that negatively regulates signals transduced by Ras proteins. Genetic and biochemical data support the hypothesis that NF1 functions as a tumor-suppressor gene in immature myeloid cells, but inactivation of both NF1 alleles has not been demonstrated in leukemic cells from patients with neurofibromatosis type 1. METHODS: Using an in vitro transcription and translation system, we screened bone marrow samples from 18 children with neurofibromatosis type 1 and myeloid disorders for NF1 mutations that cause a truncated protein. Mutations were confirmed by direct sequencing of genomic DNA from the patients, and from their affected parents, in cases of familial neurofibromatosis type 1. RESULTS: Specimens from 9 of the 18 children contained abnormal peptide fragments, and truncating mutations of the NF1 gene were found in specimens from 8 of these children. The normal NF1 allele was absent in bone marrow samples from five of the eight children. We detected the same mutation in DNA from the affected parent of each child with familial neurofibromatosis type 1. CONCLUSIONS: Both alleles of the NF1 gene are inactivated in leukemic cells in some patients with neurofibromatosis type 1. NF1 appears to function as a tumor-suppressor gene in immature myeloid cells.

Bone Marrow↗
PubMed1997

Monosomy 7 myelodysplastic syndrome and other second malignant neoplasms in children with neurofibromatosis type 1.

BACKGROUND: Children with neurofibromatosis type 1 (NF1) are at increased risk of developing benign and malignant solid tumors as well as hematologic malignancies, including de novo juvenile chronic myelogenous leukemia, monosomy 7 syndrome, and acute myelogenous leukemia. The normal NF1 allele is frequently deleted in the bone marrow cells from NF1 patients with hematologic malignancies, suggesting a pathogenic role in primary leukemogenesis. The authors report monosomy 7 myelodysplastic syndrome (MDS) as a second malignant neoplasm (SMN) in five children with sporadic NF1, the results of molecular analysis for NF1 and ras alterations in their bone marrow, and summarize their experience with SMNs in pediatric patients with NF1. METHODS: Monosomy 7 MDS was diagnosed as an SMN in five children with NF1 by morphologic and cytogenetic studies of bone marrow specimens. DNA extracted from these malignant bone marrows was analyzed for allelic loss at the NF1 locus and for the presence of ras mutations. The Children's Hospital of Philadelphia (CHOP) Tumor Registry was also reviewed to estimate the incidence of SMNs in pediatric NF1 patients. RESULTS: Bone marrow specimens from four patients retained constitutional heterozygosity at the NF1 locus; one specimen was uninformative. There was no evidence of activating ras mutations. The risk of an SMN was approximately 11% among the 64 NF1 registrants with primary malignancies in the CHOP registry, but was 75% (6 of 8) among patients treated for a pediatric embryonal cancer. CONCLUSIONS: Children with NF1 are susceptible to the development of malignant myeloid disorders both as a primary event and as an SMN. Additional molecular genetic analysis is necessary to determine if the NF1 gene is inactivated by somatic mutation in these secondary leukemias.

Blotting, Southern↗
PubMed1997

Contrast affects flicker and speed perception differently.

We have previously shown that contrast affects speed perception, with lower-contrast, drifting gratings perceived as moving slower. In a recent study, we examined the implications of this result on models of speed perception that use the amplitude of the response of linear spatio-temporal filters to determine speed. In this study, we investigate whether the contrast dependence of speed can be understood within the context of models in which speed estimation is made using the temporal frequency of the response of linear spatio-temporal filters. We measured the effect of contrast on flicker perception and found that contrast manipulations produce opposite effects on perceived drift rate and perceived flicker rate, i.e., reducing contrast increases the apparent temporal frequency of counterphase modulated gratings. This finding argues that, if a temporal frequency-based algorithm underlies speed perception, either flicker and speed perception must not be based on the output of the same mechanism or contrast effects on perceived spatial frequency reconcile the disparate effects observed for perceived temporal frequency and speed.

Contrast Sensitivity↗
PubMed1997

A detailed phenomenological comparison of complex visual hallucinations in dementia with Lewy bodies and Alzheimer's disease.

Visual hallucinations (VH) are a core feature of dementia with Lewy bodies (DLB), but little is known about their phenomenology. A total of 73 dementia patients (42 DLB, 30 Alzheimer's disease [AD], 1 undiagnosed) in contact with clinical services were assessed with a detailed standardized inventory. DLB was diagnosed according to the criteria of McKeith and colleagues, AD was diagnosed using the NINCDS-ADRDA criteria. Autopsy confirmation has been obtained when possible. VH were defined using the definition of Burns and colleagues. Detailed descriptions of hallucinatory experiences were recorded. Annual follow-up interviews were undertaken. The clinical diagnosis has been confirmed in 18 of the 19 cases that have come to autopsy. A total of 93% of DLB patients and 27% of AD patients experienced VH. DLB patients were significantly more likely to experience multiple VH that persisted over follow-up. They were significantly more likely to hear their VH speak but there were no significant differences in the other phenomenological characteristics including whether the hallucinations moved, the time of day that they were experienced, their size, the degree of insight, and whether they were complete. VH may be more likely to be multiple, to speak, and to be persistent in DLB patients. These characteristics could potentially aid accurate diagnosis.

Aged↗
PubMed1997

Health promotion training needs analysis: an integral role for clinical nurses in Lanarkshire, Scotland.

Training needs analysis is considered essential to professional and organizational development, for continuing education and for incorporation into professional practice. Increasingly, nurses are encouraged to develop their health promotion role. Despite this there has been relatively little research in Scotland into the health promotion role of the hospital nurse. This study describes the results of a health promotion training needs analysis undertaken on qualified, hospital-based nurses in Lanarkshire, Scotland. Information on the nurses' current health promotion practices, their attitudes and beliefs, their views on role development and priorities for further training were collated, analysed and discussed within the framework of the Health Action Model. This model was originally designed to assist understanding of the gap that exists between an individual intention to act and the eventual health action. However, in this study the ways in which 'cognitive factors' (knowledge and beliefs) and 'motivational factors' (considering values, attitudes and drives) and pressures from social norms and significant others assisted in the understanding of the nurse's orientation to, and beliefs about, health promotion practice. Fifty-seven per cent of nurses in the study considered health promotion activities to be emerging in clinical care and 4% considered them to be advanced. The interest respondents have in role development and the further integration of health promotion activities into nursing practice was explored by ascertaining the nurses' attitudes and beliefs about their own health promotion role. Of 107 respondents, a majority 72 (67%) agreed health promotion interventions to be an important function of the nurse with 29 (27%) strongly agreeing (n = 107). Sixty per cent stated they would be interested in developing their role and 30% were very strongly interested. Recommendations are therefore made for future planning and development strategies for the health promotion role of hospital nurses.

Adult↗
PubMed1997

CRASH syndrome: mutations in L1CAM correlate with severity of the disease.

X-linked hydrocephalus, MASA syndrome and certain forms of X-linked spastic paraplegia and agenesis of corpus callosum are now known to be due to mutations in the gene for the neural cell adhesion molecule L1 (19, 30). As a result, these syndromes have recently been reclassified as CRASH syndrome, an acronym for Corpus callosum hypoplasia, Retardation, Adducted thumbs, Spasticity and Hydrocephalus (8). A comparison of existing case reports with molecular genetic analysis reveals a striking correlation between the type of mutation in the L1CAM gene and the severity of the disease. Mutations that produce truncations in the extracellular domain of the L1 protein are more likely to produce severe hydrocephalus, grave mental retardation or early death than point mutations in the extracellular domain or mutations affecting only the cytoplasmic domain of the protein. While less severe than extracellular truncations, point mutations in the extracellular domain do produce more severe neurologic problems than mutations in just the cytoplasmic domain.

Abnormalities, Multiple↗
PubMed1997

Renal cystic disease in tuberous sclerosis: role of the polycystic kidney disease 1 gene.

Tuberous sclerosis is an autosomal dominant trait characterized by the development of hamartomatous growths in many organs. Renal cysts are also a frequent manifestation. Major genes for tuberous sclerosis and autosomal dominant polycystic kidney disease, TSC2 and PKD1, respectively, lie adjacent to each other at chromosome 16p13.3, suggesting a role for PKD1 in the etiology of renal cystic disease in tuberous sclerosis. We studied 27 unrelated patients with tuberous sclerosis and renal cystic disease. Clinical histories and radiographic features were reviewed, and renal function was assessed. We sought mutations at the TSC2 and PKD1 loci, using pulsed field- and conventional-gel electrophoresis and FISH. Twenty-two patients had contiguous deletions of TSC2 and PKD1. In 17 patients with constitutional deletions, cystic disease was severe, with early renal insufficiency. One patient with deletion of TSC2 and of only the 3' UTR of PKD1 had few cysts. Four patients were somatic mosaics; the severity of their cystic disease varied considerably. Mosaicism and mild cystic disease also were demonstrated in parents of 3 of the constitutionally deleted patients. Five patients without contiguous deletions had relatively mild cystic disease, 3 of whom had gross rearrangements of TSC2 and 2 in whom no mutation was identified. Significant renal cystic disease in tuberous sclerosis usually reflects mutational involvement of the PKD1 gene, and mosaicism for large deletions of TSC2 and PKD1 is a frequent phenomenon.

Adolescent↗
PubMed1997

Administration to humans of ORG 21465, a water soluble steroid i.v. anaesthetic agent.

Ten male volunteers received a 1-min i.v. infusion of a new water soluble steroid anaesthetic agent, ORG 21465. Individuals received doses ranging from 0.8 to 1.8 mg kg-1. All subjects experienced venous pain at the site of injection; those receiving 1.0 mg kg-1 or more became anaesthetized. There was no evidence of histamine release and apnoea did not occur. Excitatory phenomena were observed in all subjects and were dose related; no spikes were seen on the EEG. Pharmacokinetic analysis supported a three-compartment (non-weight-related) model with compartmental volumes V1, V2 and V3 of 4.31, 14.2 and 89.4 litre, respectively. Clearance from the central compartment V1 was 1.55 litre min-1. Inter-compartmental clearances Q1 and Q2 were 2.54 and 1.79 litre min-1. We found that ORG 21465 was an effective anaesthetic in humans. The relationship between sedation, anaesthesia and excitation requires further exploration.

Adult↗
PubMed1997

Striatal dopaminergic loss without parkinsonism in a case of corticobasal degeneration.

Neurochemical analyses of post-mortem brain from cases of corticobasal degeneration are extremely rare although nearly 100 cases have been reported in the literature. We detail findings of neurotransmitter derangement in the basal ganglia of a case of neuropathologically confirmed corticobasal degeneration, who presented with dementia. The implications of severe neuronal loss in the substantia nigra and extremely low levels of dopamine and its metabolites in the striatum are considered in relation to the absence of an intrinsic extrapyramidal syndrome.

Acetylcholinesterase↗
PubMed1997

Analysis of partial variance to control for day-to-day variability in functional immune tests in depression.

Recently, analysis of partial variance (APV) was proposed as a technique to control for day-to-day variance in mitogen-induced lymphoproliferative responses whereby data obtained from controls, run in the laboratory on the same day, are used as covariates in regression analysis. In order to check the utility of the APV method in the interpretation of functional immune tests, we have reanalyzed lymphoproliferative responses in experimental subjects with depression (n = 38) stimulated by phytohemagglutinin (PHA), pokeweed mitogen (PWM) and concanavalin A (Con A) in relation to responses obtained in laboratory controls. There were no significant relationships between the depressed patients' and laboratory controls' lymphoproliferative responses to PHA, PWM or Con A. Controlling for day-to-day variation by means of regression analysis did not significantly alter the significant relationships between the patients' lymphoproliferative responses and clinical variables, such as depressive classification and severity of illness. It is argued that the APV method may not be used to adjust for an inappropriately high day-to-day variability in immune assays.

Adult↗
PubMed1997

Problem-based learning at the University of Southern California School of Dentistry.

Responding to the recent Institute of Medicine report on dental education, the Center for Craniofacial Molecular Biology (CCMB) of the University of Southern California School of Dentistry has developed a parallel track program in dental education leading to the D.D.S. degree. This program was proposed in May of 1995, and the first class of twelve students was admitted in September of that year. Currently two classes are enrolled and plans to admit a further twelve students (Class of 2001) are in place. The educational strategy for this program is totally problem-based. Students work in groups of six with a faculty facilitator, not necessarily a content expert. Facilitators are largely drawn from the multidisciplinary pool of research faculty at the center. All learning is mediated through biomedical and biodental problem cases. No formal lectures or classes are scheduled. The learning of clinical dental skills is promoted through focussed dental patient simulations in which students review clinical charts, radiographs, medical reports and then explore identified, hands-on learning needs using patient simulators in a clinical context. Early patient exposure is obtained through dental office visits and other special patient clinics. Initial experience with this program suggests that the problem-based learning (PBL) students learn as well (if not better) than their traditional program peers and develop excellent group and cognitive analytical skills. The absence of a pool of dentally related biomedical cases suitable for a PBL program has necessitated the use of innovative approaches to their development and presentation. It is believed that this educational approach will produce dental clinicians equipped with the self-motivated, life-long learning skills required in the ever-changing world of bio-dental sciences in the twenty-first century.

California↗
PubMed1996

Biochemical characterization of a novel KRAS insertion mutation from a human leukemia.

A novel alteration in exon 1 of KRAS was detected by single strand conformational polymorphism analysis of DNA amplified from the bone marrow of a 4-year-old child with myeloid leukemia. Sequencing of this mutant allele revealed an insertion of three nucleotides between codons 10 and 11 resulting in an in-frame insertion of glycine. Expression of the mutant protein in NIH 3T3 cells caused cellular transformation, and expression in COS cells activated the Ras-mitogen-activated protein kinase signaling pathway. Surprisingly, Ras.GTP levels measured in COS cells established that this novel mutant accumulates to 90% in the GTP state, considerably higher than a residue 12 mutant. Biochemical analysis confirmed that the higher Ras.GTP levels correspond to a dramatic decrease in intrinsic GTP hydrolysis as well as resistance to GTPase-activating proteins. This mutation is the first dominant Ras mutation found in human cancer that does not involve residues 12, 13, or 61, and its biochemical properties should help elucidate the mechanism of oncogenic activation.

3T3 Cells↗
PubMed1996

Patterns of hematopoietic lineage involvement in children with neurofibromatosis type 1 and malignant myeloid disorders.

Children with neurofibromatosis type 1 (NF1) are at increased risk of developing malignant myeloid disorders, particularly juvenile chronic myelogenous leukemia/juvenile myelomonocytic leukemia (JCML/JMML). We investigated bone marrows from 11 such patients (8 boys and 3 girls) and detected allelic losses at the NF1 locus in 4 of them and probable losses in 2 others. To determine which hematopoietic cell lineages were derived from the abnormal clones, Epstein-Barr virus (EBV)-transformed cell lines and CD34+ cells were analyzed from 3 children with JCML with allelic losses in unfractionated marrow. CD34 cells from these 3 patients lacked the normal NF1 allele, whereas EBV cell lines retained it. Erythroblasts plucked from the burst-forming unit-erythroid colonies of one of these children lacked the normal NF1 allele. We also studied a 10-month-old boy with NF1 who developed an unusual myeloproliferative syndrome. His bone marrow and EBV cell line both showed loss of the normal NF1 allele. In our series and in the literature, male sex and maternal transmission of NF1 were associated with the highest risk of myeloid leukemia. These data (1) provide strong genetic evidence that NF1 functions as a tumor-suppressor in early myelopoiesis, (2) confirm the clonal nature of JCML/JMML, (3) suggest that the elevation in fetal hemoglobin seen in JCML/JMML is a result of primary involvement of erythroid progenitors in the malignant clone, (4) show consistent loss of NF1 in the CD34 cells of affected children and show that the malignant clone may also give rise to pre-B cells in some cases, and (5) implicate epigenetic factors in the development of leukemia in children with NF1.

Acute Disease↗
PubMed1996

Identification of a surface glycoprotein on African green monkey kidney cells as a receptor for hepatitis A virus.

Very little is known about the mechanism of cell entry of hepatitis A virus (HAV), and the identification of cellular receptors for this picornavirus has been elusive. Here we describe the molecular cloning of a cellular receptor for HAV using protective monoclonal antibodies raised against susceptible African green monkey kidney (AGMK) cells as probes. Monoclonal antibodies 190/4, 235/4 and 263/6, which reacted against similar epitopes, specifically protected AGMK cells against HAV infection by blocking the binding of HAV. Expression cloning and nucleotide sequence analysis of the cDNA coding for epitope 190/4 revealed a novel mucin-like class I integral membrane glycoprotein of 451 amino acids, the HAV cellular receptor 1 (HAVcr-1). Immunofluorescence analysis indicated that mouse Ltk- cells transfected with HAVcr-1 cDNA gained limited susceptibility to HAV infection, which was blocked by treatment with monoclonal antibody 190/4. Our results demonstrate that the HAVcr-1 polypeptide is an attachment receptor for HAV and strongly suggest that it is also a functional receptor which mediates HAV infection. This report constitutes the first identification of a cellular receptor for HAV.

Amino Acid Sequence↗