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M Davidson

Publications and source records attributed to M Davidson.

At least 91 records · Page 5Linked to original sources
PubMed1997

Murine macrophage mannose receptor promoter is regulated by the transcription factors PU.1 and SP1.

The mannose receptor (MR) is a transmembrane protein that functions primarily as a phagocytic receptor for a wide range of microorganisms. Its expression appears to be restricted to tissue macrophages and Langerhans cells. To gain an understanding of the regulation of the gene, we have isolated the 5' flanking sequence of the murine MR gene and have analyzed a 536-bp sequence upstream of the ATG start site for transcriptional activity. This sequence lacks a TATA box but contains an initiator (Inr) consensus element overlapping the single transcriptional start site. Transcription factor binding sites contained within this sequence include PU.1, Sp1, ETS, GATA, and MYB motifs. Serial 100-bp deletions of this promoter fragment fused to a luciferase reporter gene showed various patterns of activity when transfected into different cell types. In myeloid cells, sequence elements upstream of bp -300 appeared to have a silencing effect on promoter activity. Of the four potential PU.1 binding sites contained within the fragment, one site (at -164) bound the PU.1 factor most strongly, whereas the adjacent PU.1 site (at -177 bp) bound PU.1 to a lesser degree. Mutations of these sites decreased transcriptional activity but did not abolish it. However, promoter activity was abrogated when both the -164 bp PU.1 site and the adjacent -177 bp PU.1 site were mutated. In addition, mutation of the Sp1 site also significantly reduced promoter activity. Cotransfection studies in Drosophila Schneider cells indicated that PU.1 and Sp1 may function synergistically in transactivating the murine MR. This study indicates that MR gene expression is regulated in part by the interaction between the ubiquitously expressed factor Sp1 and the lymphoid/myeloid factor PU.1 and provides a basis for studying the regulation of this gene.

Animals↗
PubMed1997

The association between adaptive and cognitive deficits in geriatric chronic schizophrenic patients.

Cognitive impairments have been shown to predict impairments in adaptive functioning in patients with chronic schizophrenia and to be more predictive of overall outcome than positive or negative symptoms of the illness. Both adaptive and cognitive impairments are multidimensional, and it is possible that correlations between these domains may be limited to certain aspects of these functions. In this study, 208 geriatric patients with chronic schizophrenia were examined with a cognitive battery and assessed with a structured scale to determine the extent of their adaptive functions. Instrumental and social skills deficits were more strongly correlated with cognitive impairments than with the severity of undercontrolled behavior. Each of the cognitive measures was correlated with global social-adaptive deficits, with minimal variation in the magnitude of correlations. These results suggest that interventions should be individually targeted to cognitive-adaptive impairments and undercontrolled behavior.

Age Factors↗
PubMed1997

Limitations of controlled augmentation trials in schizophrenia.

To assess the empirical basis for add-on augmentation treatments in schizophrenia, this study examined the experimental design components of pharmacologic augmentation trials in schizophrenia and compared them to conventional requirements. A search covering a 5-year period (1988-1992) identified 13 double-blind, placebo-controlled, parallel, add-on neuroleptic augmentation drug trials. The mean number of subjects per trial was 34.5, and the mean number of outcome measures examined was 25.0. The probability for a significant finding by chance was 63%. Mean effect size required to achieve conventional statistical power was 1.6. Mean statistical power (for effect sizes of .5-1.0) was .1-.4. The mean number of subjects actually required for power of .80 was 58-216. The majority of the 13 trials included too few patients and employed too many outcome measures to conclusively prove or disprove therapeutic efficacy. Conclusions drawn from such trials with less than 40-100 subjects or more than one hypothesis must remain tentative at best.

Antipsychotic Agents↗
PubMed1997

Comparison of one-year efficacy and safety of atorvastatin versus lovastatin in primary hypercholesterolemia. Atorvastatin Study Group I.

This double-blind study to evaluate long-term efficacy and safety of atorvastatin was performed in 31 community- and university-based research centers in the USA to directly compare a new 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (reductase inhibitor) to an accepted drug of this class in patients with moderate hypercholesterolemia. Participants remained on a cholesterol-lowering diet throughout the study. One thousand forty-nine patients were randomized to receive atorvastatin 10 mg, lovastatin 20 mg, or placebo. At 16 weeks the placebo group was randomized to either atorvastatin or lovastatin treatment. At 22 weeks, patients who had not met low-density lipoprotein (LDL) cholesterol target levels doubled the dose of reductase inhibitor. Efficacy evaluation was mean percent change from baseline in LDL cholesterol, triglycerides, total cholesterol, high-density-lipoprotein cholesterol, and apolipoprotein B (apoB). Safety profiles as determined by change from baseline in laboratory evaluations, ophthalmologic parameters, and reporting of adverse events were similar for the 2 reductase inhibitors. After 52 weeks, the atorvastatin group maintained a significantly greater reduction in LDL cholesterol (-37% vs -29%), triglyceride (-16% vs -8%), total cholesterol (-27% vs -21%), and apoB (-30% vs -22%) (p <0.05). More patients receiving atorvastatin achieved LDL cholesterol target levels than did lovastatin patients (78% vs 63%, respectively), particularly those with coronary heart disease (37% vs 11%, respectively). Atorvastatin is highly effective and well tolerated in patients with primary hypercholesterolemia with no increased risk of adverse events.

Analysis of Variance↗
PubMed1997

Interaction of the adaptor protein Shc and the adhesion molecule cadherin.

In mitogenic signaling pathways, Shc participates in the growth factor activation of Ras by interacting with activated receptors and/or the Grb-2.Sos complex. Using several experimental approaches we demonstrate that Shc, through its SH2 domain, forms a complex with the cytoplasmic domain of cadherin, a transmembrane protein involved in the Ca2+-dependent regulation of cell-cell adhesion. This interaction is demonstrated in a yeast two-hybrid assay, by co-precipitation from mammalian cells, and by direct biochemical analysis in vitro. The Shc-cadherin association is phosphotyrosine-dependent and is abrogated by addition of epidermal growth factor to A-431 cells maintained in Ca2+-free medium, a condition that promotes changes in cell shape. Shc may therefore participate in the control of cell-cell adhesion as well as mitogenic signaling through Ras.

3T3 Cells↗
PubMed1997

Human papillomavirus type 16 DNA in esophageal carcinomas from Alaska Natives.

The possible etiological role of human papillomavirus (HPV) in esophageal carcinogenesis was evaluated in Alaska Natives in whom the incidence of esophageal cancer is 1.3 and 3.8 times higher than in US Caucasian men and women, respectively. Fixed paraffin-embedded esophageal tissues from 32 cases of squamous-cell carcinoma (SCC) and 3 cases of adenocarcinoma (AC) diagnosed between 1957 and 1988 were analyzed by polymerase chain reaction (PCR) and in situ hybridization for HPV DNA sequences. Detection of the human beta-globin gene by PCR was used as a control for sufficiency of DNA and its potential for amplification in the tissue samples. Twenty-five of the tumor tissues were considered adequate for PCR analyses; HPV DNA was detected in 10 of 22 SCCs and was not found in 3 ACs. Seven of the 10 HPV-positive tissues contained sequences from the E6 gene of HPV type 16. Koilocytosis, an epithelial change consistent with HPV infection, was found in 80% of the esophageal squamous-cell tumors with HPV DNA and in 75% of those without HPV DNA. The detection of amplifiable cellular DNA was related to recentness of diagnosis; however, the detection of HPV DNA within amplifiable specimens was not related to recentness of diagnosis. A 413-bp sequence from the L1 open reading frame of HPV 16 from esophageal tissue of 2 patients was identical to sequences previously identified in cervical cells from other Alaska Natives. Our results provide molecular evidence of HPV infection, especially type 16, in archival esophageal cancer tissues from 45% of those patients whose specimens contain adequate DNA for PCR analysis.

Adenocarcinoma↗
PubMed1997

Increased concentrations of presynaptic proteins in the cingulate cortex of subjects with schizophrenia.

BACKGROUND: Cytoarchitectural and neurochemical studies demonstrate disorganization in the cerebral cortex in schizophrenia, which perhaps underlies the severe behavioral disturbances of the disease. This neuronal disarray should be accompanied by synaptic abnormalities. As such, presynaptic proteins have proved valuable indexes of synaptic density and their concentrations have correlated markedly with synaptic loss. Our study sought to determine whether abnormalities exist in the concentrations of presynaptic proteins in the postmortem cerebral cortex of subjects with schizophrenia. METHODS: Presynaptic protein immunoreactivities were assessed in 4 different cerebrocortical regions derived from 16 elderly controls, 19 elderly subjects with schizophrenia, and 24 subjects with Alzheimer's disease. Tissues were assayed with the monoclonal antibodies EP10 and SP4, which recognize synaptophysin, and the monoclonal antibodies SP6 and SP14, which detect syntaxin and synaptosomal-associated protein-25-kd immunoreactivities, respectively. RESULTS: In subjects with schizophrenia relative to controls, presynaptic proteins were increased in the cingulate cortex, but were unchanged in the temporal, frontal, and parietal cortices. In contrast, when cases with Alzheimer's disease were compared with controls, presynaptic proteins were decreased in the frontal, temporal, and parietal samples. CONCLUSIONS: These findings reveal changes in the synaptic organization of the cingulate cortex in schizophrenia relative to other areas examined. These changes are distinct from the deficits in presynaptic proteins observed in Alzheimer's disease.

Alzheimer Disease↗
PubMed1997

Dopamine receptor transcript expression in striatum and prefrontal and occipital cortex. Focal abnormalities in orbitofrontal cortex in schizophrenia.

BACKGROUND: The identification of novel subtypes of the dopamine receptors has renewed interest in the involvement of dopaminergic mechanisms in schizophrenia. We determined the expression of transcripts encoding the dopamine receptors in the brains of schizophrenic patients. METHODS: The levels of the messenger RNA molecules encoding the 5 dopamine receptors were quantified in postmortem brain samples from 16 schizophrenic patients and 9 control subjects. Samples from multiple regions of the prefrontal cortex, primary visual cortex, and striatum were subjected to in situ hybridization followed by quantitative image analysis. RESULTS: Expression of dopamine receptor transcripts did not differ between schizophrenic patients and controls in striatum or visual cortex. Dramatic decreases of dopamine receptor transcripts were found in the prefrontal cortex, but these changes were restricted to the D3 and D4 receptors, and localized to Brodmann area 11 (orbitofrontal cortex). CONCLUSIONS: Cortical dopaminergic neurotransmission may be disrupted in schizophrenia at the level of receptor expression. There appears to be a focal abnormality of D3 and D4 messenger RNA expression in the prefrontal cortex, with down-regulation of both, consistent with prefrontal cortical hypodopaminergia in schizophrenia.

Aged↗
PubMed1997

Characteristics of elderly psychiatric patients retained in a state hospital during downsizing: a prospective study with replication.

OBJECTIVE: This study examined the clinical characteristics of elderly inpatients associated with retention in a large state hospital during a period of rapid reduction in the inpatient census. DESIGN: During the first year of the study all inpatients age 65 or greater were individually evaluated. Patients remaining in the hospital during the second year were reevaluated and followed for an additional year. Separate statistical analysis of the data allowed for replication of findings. SETTING: The study was conducted at Pilgrim Psychiatric Center, the largest state hospital in New York State. PARTICIPANTS: The entire inpatient population over the age of 65 were included in the study (N = 806). The average age of the sample was 76 years and 70% were assigned a lifetime research diagnosis of schizophrenia. The majority of patients were hospitalized for long periods (mean = 33.9 years) and had significant cognitive impairment. MAIN OUTCOME MEASURES: Cognitive functioning was assessed on the Clinical Dementia Rating Scale. Severity of psychiatric symptoms was evaluated on the PANSS. Occurrence of dangerous behavior and medical and psychiatric treatment were obtained from the patients' medical histories. MAIN RESULTS: The findings, replicated across assessments, were that patients retained had more severe symptoms of excitement, hostility and impulsive behavior than those discharged, while uncooperativeness, delusions, grandiosity and suspiciousness were also more severe in those retained than those discharged. CONCLUSIONS: Elderly patients who are very difficult to place are so characterized because of behavior disorders that are difficult to manage rather than psychotic symptoms, cognitive impairment or medical disorders.

Aged↗
PubMed1997

Cognitive impairment in geriatric chronic schizophrenic patients: a cross-national study in New York and London.

Severe cognitive impairment has been reported in large numbers of geriatric chronic schizophrenic patients in the US, with this impairment also being related to severe negative symptoms and adaptive deficits. It is not clear if this impairment is related to the particular environment of the American state hospitals and would not generalize to other countries. In this study, a sample composed of geriatric (age > 70) chronic schizophrenic patients in London, who were assessed by the Team for Assessment of Psychiatric Services (TAPS) (N = 137), and a group of geriatric chronic schizophrenic patients in a New York psychiatric center (N = 86) were compared for the severity of cognitive impairment and on measures of adaptive functioning. Patients received essentially identical Mini-Mental State Examination (MMSE) scores, but differed on 3/4 measures of adaptive functioning. The correlations among all four aspects of adaptive deficit and MMSE scores were very similar in the two samples, suggesting that cognitive deficits and their relationship with adaptive impairments are relatively invariant across different psychiatric systems of care, while adaptive functioning deficits are more variable and possibly more influenced by environmental factors. These data add to previous results suggesting that cognitive impairment is a common feature in poor outcome geriatric patients with schizophrenia.

Aged↗
PubMed1997

Immediate early gene expression and delayed cell death in limbic areas of the rat brain after kainic acid treatment and recovery in the cold.

Systemic injection of kainic acid (KA) results in characteristic behaviors and programmed cell death in some regions of the rat brain. We used KA followed by recovery at 4 degrees C to restrict damage to limbic structures and compared patterns of immediate early gene (IEG) expression and associated DNA binding activity in these damaged areas with that in spared brain regions. Male Wistar rats were injected with KA (12 mg/kg, i.p.) and kept at 4 degrees C for 5 h. This treatment reduced the severity of behaviors and restricted damage (observed by Nissl staining) to the CA1 and CA3 regions of the hippocampus and an area including the entorhinal cortex. DNA laddering, characteristic of apoptosis, was first evident in the hippocampus and the entorhinal cortex 18 and 22 h after KA, respectively. The pattern of IEG mRNA induction fell into three classes: IEGs that were induced in both damaged and spared areas (c-fos, fos B, jun B, and egr-1), IEGs that were induced specifically in the damaged areas (fra-2 and c-jun), and an IEG that was significantly induced by saline injection and/or the cold treatment (jun D). The pattern of immunoreactivity closely followed that of mRNA expression. Binding to the AP-1 and EGR DNA consensus sequences increased in all three regions studied. This study describes a unique modification of the animal model of KA-induced neurotoxicity which may prove a useful tool for dissecting the molecular cascade that ultimately results in programmed cell death.

Animals↗
PubMed1997

Social-Adaptive Functioning Evaluation (SAFE): a rating scale for geriatric psychiatric patients.

Geriatric chronic psychiatric inpatients often remain in a chronic psychiatric hospital because of serious deficits in adaptive life functions. Because the additional complications and adaptive changes associated with aging have not been considered in previous scales, the Social-Adaptive Functioning Evaluation (SAFE) was developed. The items in the scale measure social-interpersonal, instrumental, and life skills functioning and are designed to be rated by observation, caregiver contact, and interaction with the subject if possible. Interrater and test-retest reliability were examined (n = 60) and convergent and discriminant validity were rated against other relevant measures (n = 50) in separate studies, with all being found adequate. The factor structure of the scale was examined with exploratory factor analysis, revealing a three-factor structure. Finally, predictive validity was examined in a preliminary study of 140 patients, 45 of whom were discharged after the assessment. The results indicate that patients who remained hospitalized could be discriminated from those who were sent to nursing homes or community care on the basis of certain SAFE items and subscales. These results support the use of this instrument in later studies of geriatric psychiatric patients.

Activities of Daily Living↗
PubMed1997

Six new DPB1 alleles identified in a study of 1,302 unrelated bone marrow donor-recipient pairs.

Six new DPB1 alleles were identified by PCR-SSOP methodologies in the course of a retrospective study of the role of HLA matching in the outcome of unrelated donor bone marrow transplantation. Sequencing confirmed that five of these alleles (DPB1*5901, *6801, *7101, *7201, and *7301) represent novel combinations of previously described sequence motifs in the variable regions of DPB1; the sixth (DPB1*7001) appears to result from a novel point mutation. These data support previous observations which suggest that multiple mechanisms, including segmental exchange and mutation, appear to be responsible for generating sequence diversity at the DPB1 locus. The extremely low discrepancy rate of 0.1% between the two laboratories which typed the samples, and the ability to predict the new sequences from probe hybridization patterns, indicate that SSOP is an accurate and efficient method for studying polymorphism at DPB1.

Alleles↗
PubMed1997

Identification of the DRB1*1313 allele in a sibling pair.

Sequence-specific oligonucleotide probe hybridization (PCR/SSOP), which is now routinely used in HLA laboratories to type for alleles of the class II loci, can also detect the presence of previously unknown alleles. In the course of clinical typing for DRB1, we identified two samples with probe hybridization patterns appropriate for DRB1*1313, a previously submitted sequence that had been withdrawn. Direct sequencing showed that the two individuals carried an allele with an exon 2 sequence identical to that previously submitted for DRB1*1313.

Alleles↗
PubMed1997

Age-related differences in formal thought disorder in chronically hospitalized schizophrenic patients: a cross-sectional study across nine decades.

OBJECTIVE: This study used a cross-sectional design to examine the frequency of occurrence and severity of 10 different signs of thought disorder in schizophrenic patients across the lifespan. METHOD: Schizophrenic patients, who ranged in age from 19 to 96 years (N = 392), were examined with the Scale for Assessment of Thought, Language, and Communication. The cognitive functioning of the geriatric patients (patients over the age of 64, N = 120) was also assessed. RESULTS: Poverty of speech was more common and more severe in geriatric patients, while four different signs of thought disorder that reflect disconnected speech were less common and less severe in geriatric patients. Analysis of covariance found that the lower severity of disconnection thought disorders in the older patients was not attributable to differences in the amount of speech produced. CONCLUSIONS: Aspects of disconnected speech were less severe in older patients, while the severity and frequency of poverty of speech were greater. These findings suggest that the two previously identified separate dimensions of communication disorder in schizophrenia vary differently with age and possibly in their cognitive and biological underpinnings.

Adult↗
PubMed1997

Verbal fluency deficits in geriatric and nongeriatric chronic schizophrenic patients.

This study examined age-related differences and correlates of deficits on phonological and category fluency tasks performed by schizophrenic patients. Equal numbers (n = 41) of geriatric (age > 64) and nongeriatric chronically hospitalized schizophrenic patients were examined with tests of phonological and category fluency, verbal learning and delayed recall, confrontation naming, and reading, as well as overall estimates of cognitive impairment. Both types of fluency tests were performed very poorly by both groups. Age-related differences were found to be statistically significant. In both groups, category fluency impairments were correlated with deficits in naming, while phonological fluency deficits were best predicted by memory impairments. These data suggest that category fluency impairments are part of a general profile of impaired semantic functioning, whereas phonological fluency deficits may be induced by alterations in information processing capacity.

Aged↗