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Biomedical subjects

P Lambert

Publications and source records attributed to P Lambert.

At least 19 recordsLinked to original sources
PubMed1999

Alveolar clearance in horses with chronic obstructive pulmonary disease.

OBJECTIVE: To assess sensitivity of scintigraphic alveolar clearance rate as an indicator of alveolar epithelium damage in horses. ANIMALS: 5 healthy horses (group A) and 5 with chronic obstructive pulmonary disease (COPD; group B). PROCEDURE: Horses underwent clearance rate (k [%/min]) determination. Clearance rate of group-B horses was determined after remission of the disease following 2 months at pasture (remission 1), stabling in a controlled environment (remission 2), and during crisis induced by exposure to moldy hay and straw. Methacholine challenge test was performed at each investigation period to determine nonspecific pulmonary airway hyperresponsiveness. Pulmonary function tests (PFT) also were performed, and cell populations in bronchoalveolar lavage (BAL) fluid were determined on another occasion. RESULTS: Group-B horses had significantly faster mean clearance rate during crisis (k = 4.30+/-0.95%/min), compared with that for remission 1(k = 1.98+/-0.55%/min), which did not differ from the rate in group-A horses (k = 1.95+/-0.33%/min). Despite lack of clinical signs of COPD during remission when stabled in a controlled environment, an intermediate value was found (k = 3.20+/-0.72%/min). CONCLUSIONS: This technique allowed grading of lung damage induced by COPD, whereas use of PFT and determination of BAL fluid cell populations failed to differentiate between remission 1 and remission 2. CLINICAL RELEVANCE: Determination of alveolar clearance rate by use of scintigraphy is a sensitive indicator of lung damage. A modified clearance rate was found despite the lack of clinical and functional changes.

Animals↗
PubMed1998

Mice expressing the E7 oncogene of HPV16 in epithelium show central tolerance, and evidence of peripheral anergising tolerance, to E7-encoded cytotoxic T-lymphocyte epitopes.

In order to derive mice which expressed both the E7 open reading frame transgene of human papillomavirus type 16 in skin and MHC class 1 restriction elements for several E7-encoded cytotoxic T-lymphocyte (CTL) epitopes, K14.HPV16E7 mice which express E7 in basal keratinocytes were crossed to the F1 generation with A2.1 Kb transgenic mice which express the MHC binding cleft domains of human HLA A*0201, and murine H-2b. F1 mice (denoted K14E7 x A2.1) expressed E7 in the thymus at least as early as 2-5 days before birth. Immunisation of FVB x A2.1 control mice (transgenic for HLA A*0201 and H-2b but not for E7), with two HLA A*0201-restricted epitopes of E7 and one H-2b-restricted CTL epitope of E7, gave strong primary CTL responses recognising epitope-pulsed or constitutively E7-expressing syngeneic target cells. In contrast, in immunised K14E7 x A2.1 mice, the CTL responses to the H-2b epitope and one of the HLA A*0201 CTL epitopes were strongly down-regulated, and to the other HLA A*0201 epitope, completely abolished, as demonstrated by percentage specific killing by bulk splenocyte cultures in cytotoxicity assays, and by CTL precursor frequency analysis. In thymus-transplanted bone marrow radiation chimeras in which the immune system of K14E7 x A2.1 mice was replaced by a FVB x A2.1 immune system, specific immunisation did not result in reemergence of strong E7-directed CTL responses. In agreement with these in vitro findings, specific immunisation failed to significantly alter the course of E7-associated tumour development in K14E7 x A2.1 mice. These data are consistent with a model of central deletional CTL tolerance to E7-encoded epitopes recognised in the context of two distinct MHC class 1 restriction elements, and with the possibility of peripheral T-cell anergy maintained by expression of E7 in the skin.

Amino Acid Sequence↗
PubMed1998

On the appropriateness of marginal models for repeated measurements in clinical trials.

Although models developed directly to describe marginal distributions have become widespread in the analysis of repeated measurements, some of their disadvantages are not well enough known. These include producing profile curves that correspond to no possible individual, possibly showing that a treatment is superior on average when it is poorer for each individual subject, implicitly generating complex and implausible physiological explanations, including underdispersion in subgroups, and sometimes corresponding to no possible probabilistic data generating mechanism. We conclude that such marginal models may sometimes be appropriate for descriptive observational studies, such as sample surveys in epidemiology, but should only be used with great care in causal experimental settings, such as clinical trials.

Clinical Trials as Topic↗
PubMed1998

Scintigraphical evaluation of alveolar clearance in horses.

This study proposed a standardized method for measuring alveolar epithelium membrane permeability in the horse. The normal rate of clearance (%.min-1) from lung into blood of nebulized 99mTc-DTPA has been established for healthy horses (Group A) compared with values obtained with horses suffering from chronic obstructive pulmonary disease (COPD; Group B). The 99mTc-DTPA clearance was measured in the caudoventral (R1) and in the half caudal (R2) parts of the left lung during different time intervals. The two regions aimed to define the influence of the airways on measured clearance (R2 contained proportionally more conducting airways than R1). It was concluded that a comparison of groups of subjects may be performed in R2 and on data collected during a 20 min period. The normal clearance rate in R2 was 1.80 +/- 0.46%.min-1 (T1/2R2 = 40.99 +/- 12.45 min) in Group A. In Group B, a significantly faster 99mTc-DTPA transfer rate was found (4.17 +/- 0.83%.min-1 or T1/2R2 = 17.17 +/- 3.38min). Bronchoalveolar lavage (BAL) suggested that the increased permeability measured in Group B could be the result of lung inflammatory responses. Our results have demonstrated the ability of the 99mTc-DTPA clearance test to detect alveolar epithelial damage in horses. Furthermore, we were able to show that a regional analysis of the alveolar-capillary barrier integrity may be performed satisfactorily in the equine patient.

Animals↗
PubMed1997

E7 oncoprotein of human papillomavirus type 16 expressed constitutively in the epidermis has no effect on E7-specific B- or Th-repertoires or on the immune response induced or sustained after immunization with E7 protein.

A line of FVB (H-2q) mice transgenic for the E6/E7 open reading frames of Human Papillomavirus type 16 driven from the alpha-A crystallin promoter expresses E7 mRNA in lens and skin epithelium. E7 protein is detectable in adult skin, coinciding with the development of inflammatory skin disease, which progresses to papillomata and squamous carcinomata in some mice. By examining the outcome of parenteral immunization with E7 protein, we sought to determine whether endogenous expression of E7 in skin had induced a preexisting immune outcome, i.e., specific immunity or tolerance, or whether the mice remain naive ("ignorant") to E7. Our data show that the antibody response to defined E7 B-epitopes, the proliferative response to Th epitopes, and the delayed-type hypersensitivity (DTH) response to whole E7 did not differ between groups of young and old E6/E7 transgenic mice (likely having different degrees of lifetime exposure to E7 protein) or between E6/E7-transgenic and nontransgenic parental strain control mice. Although an E7-specific CTL response could not be induced in the H-2q background of these mice, incorporation of a Db allele into the genome allowed comparison of Db-restricted CTL responses in E6/E7 transgenic and nontransgenic mice. Experiments indicated that the E7-immunization-induced CTL response did not differ significantly between E6/E7 transgenic and nontransgenic mice. We interpret these results to indicate that in spite of expression of E7 protein in adult skin, E6/E7 transgenic mice remain immunologically naive (ignorant) of E7 epitopes presented by immunization.

Amino Acid Sequence↗
PubMed1997

High level expression of the capsid protein of hepatitis E virus in diverse eukaryotic cells using the Semliki Forest virus replicon.

The capsid protein of hepatitis E virus (HEV) is encoded by open reading frame 2 (ORF 2) and exhibits variable processing when expressed in insect and COS cells, but nothing is known of its processing in cells relevant to its replication. The full-length ORF 2 protein was expressed at high levels in mammalian cells by insertion of ORF 2 in the Semliki Forest virus (SFV) replicon to generate rSFV/HEV ORF 2K. Expression of the capsid protein was detected readily by metabolic labelling and indirect immunofluorescence in BHK-21 cells transfected with RNA transcripts derived from rSFV/HEV ORF 2K. ORF 2 protein was also expressed at high levels in cells of diverse origin, including liver-derived cell lines Huh7 and HepG2, following infection with recombinant virus derived from cotransfection of BHK-21 cells with the rSFV/HEV ORF 2K and helper SFV replicon RNAs. The addition of hypertonic KCl during metabolic labelling reduced the level of host cell protein synthesis and enhanced the detection of intermediates in ORF 2 protein processing. The wide host range and high level expression directed by SFV replicon particles has particular utility in the analysis of cell-specific factors in the protein processing and assembly of non-cultivable viruses such as HEV.

Animals↗
PubMed1997

Activity of protein MalE (maltose-binding protein) fused to cytoplasmic and periplasmic regions of an Escherichia coli inner membrane protein.

We analysed the properties of mature MBP (maltose-binding protein or MalE protein) fused to an integral cytoplasmic membrane protein of Escherichia coli. Fusion of MalE to the first MalG periplasmic loop enabled a strain defective in the malE gene to utilize maltose. In contrast, fusion of MalE to a cytoplasmic loop did not complement the malE delta 444 deletion. We obtained results highly correlated with those obtained by using alkaline phosphatase as a reporter for the topology of MalG. We discuss the possibility of genetically determining the topology of cytoplasmic membrane proteins by a method based on engineered fusions to MBP.

ATP-Binding Cassette Transporters↗
PubMed1997

Constitutive expression of p50 homodimer in freshly isolated human monocytes decreases with in vitro and in vivo differentiation: a possible mechanism influencing human immunodeficiency virus replication in monocytes and mature macrophages.

Human immunodeficiency virus type 1 (HIV-1) replicates more efficiently in vitro in differentiated macrophages than in freshly isolated monocytes. We investigated whether this may be partly explained by changes in expression of NF-kappaB with monocyte differentiation. We demonstrated that constitutive expression of NF-kappaB in primary human monocytes changed significantly with differentiation in vitro to monocyte-derived macrophages (MDMs) and differentiation in vivo to alveolar macrophages (AMs). Freshly isolated monocytes constitutively expressed high levels of transcriptionally inactive p50 homodimer which decreased with time in culture in favor of the transcriptionally active p50/p65 and p50/RelB heterodimers. As in MDMs, AMs constitutively expressed p50/p65 and p50/RelB although at lower levels. HIV infection of fresh monocytes failed to induce p50/p65 as seen in MDMs. The replacement of p50 homodimers with transcriptionally active heterodimers following time in culture may partially explain the progressive increase in susceptibility of monocytes to HIV infection during in vitro culture. The change in NF-kappaB components with monocyte differentiation in vivo may also explain the different transcriptional activities of these cell populations in HIV-infected individuals.

Cell Differentiation↗
PubMed1997

Effects of negative allosteric modulators of gamma-aminobutyric acidA receptors on complex behavioral processes in monkeys.

A multiple schedule of repeated acquisition and performance of conditional discriminations was used to characterize the effects of two negative allosteric modulators of the gamma-aminobutyric acid (GABAA) receptor (ethyl beta-carboline-3-carboxylate [beta-CCE] and N-methyl-beta-carboline-3-carboxamide [FG-7142]), a hallucinogenic beta-carboline derivative (harmine), a benzodiazepine receptor antagonist (flumazenil) and a positive allosteric modulator (alprazolam). In the acquisition component, subjects acquired a different discrimination each session. Acquisition of a discrimination was defined by a decrease in errors as the session progressed. In the performance component, the discrimination was the same each session. Responding in both components was maintained by food presentation under a variable-ratio schedule. Incorrect responses in both components produced a 5-sec timeout. Alprazolam (0.1-18 mg/kg), beta-CCE (0.01-0.32 mg/kg), FG-7142 (0.1-18 mg/kg) and harmine (0.1-1.8 mg/kg) all dose-dependently decreased response rate in both components. However, accuracy of responding-was differentially affected by the drugs. Alprazolam selectively and dose-dependently increased percent errors in acquisition, whereas beta-CCE increased acquisition errors only at the highest doses tested in each subject. In contrast, FG-7142 and harmine had no effects on percent errors at doses that virtually eliminated responding. In all cases, performance accuracy was generally not affected. Flumazenil, at doses that had little or no effect (0.1 and 0.32 mg/kg) or occasionally decreased response rates (1 mg/kg) when administered alone, dose-dependently antagonized the rate-decreasing and error-increasing effects of beta-CCE, FG-7142 and alprazolam. In contrast, flumazenil failed to antagonize the effects of harmine. Thus, the negative allosteric modulators only moderately disrupted acquisition in comparison with the positive allosteric modulator, but the effects of both types of modulator were antagonized by the benzodiazepine antagonist flumazenil.

Allosteric Regulation↗
PubMed1997

[Long-term outcome at adjacent levels of lumbar arthrodesis].

Posterolateral lumbar fusion is commonly recognized to have a significant effect upon the more proximal unfused segments. Wether these effects are clinically significant remains unclear. Long term studies with standardized follow-up are scarce. The purpose of this study was to examine the long term roentgenographic and clinical effects of posterolateral fusion upon the 3 cephalad unfused segments. The levels below a floating fusion were also examined. The factors promoting the occurrence of degenerative changes on standard or dynamic x rays were also investigated with a multivariate analysis model. 102 patients who underwent a posterolateral fusion were retrospectively reviewed with an average follow-up of 8.9 years. 39 patients (group I) were fused for low back pain caused by isthmic lysis spondylolisthesis, 15 (group II) for degenerative disc disease and 48 (group III) in addition to a posterior decompression for a lumbar spinal stenosis. Pre and postoperative standard and dynamic roentgenograms were compared in order to study: evolution of the disc space height, modifications in the angular and antero-posterior mobility, modifications in the antero-posterior displacement of the vertebral bodies. Degenerative changes were frequent. 49 per cent of the patients demonstrated a severe disc space narrowing, 30 per cent developed a degenerative spondylolisthesis, 32 per cent an angular hypermobility and 35 per cent an antero-posterior hypermobility. Only one factor was found to increase significantly the occurrence of degenerative changes: the indication of lumbar fusion. Degenerative changes were significantly more frequent in group III's patients. However, no significant correlation was found between the roentgenographic findings and the final functional results and only 8 patients required a new surgery. These results may suggest that posterolateral fusion accelerates the development of degenerative changes in adjacent discs if the fusion is performed on a degenerative spine.

Adolescent↗
PubMed1996

Modelling irregularly sampled profiles of non-negative dog triglyceride responses under different distributional assumptions.

General methodology for modelling series of non-negative data observed at unequally spaced times is developed. The parameterization enables both the importance of the serial association, as well the 'order' of this dependence to be expressed. An example is given where the effects of three fibre based diets on dog triglyceride profiles are analysed and compared. Many different types of models based on common distributions such as the normal, exponential, gamma, Weibull and log-normal observations are presented. Comparison of possibly non-nested models fitted on the same data set is made using the Akaike criterion.

Animals↗
PubMed1996

Molecular phylogeny of eastern Pacific sea cucumbers (Echinodermata: Holothuroidea) based on mitochondrial DNA sequence.

A molecular phylogenetic analysis of some Holothuroidea was undertaken in order to clarify the systematics and taxonomy of this class in the northeast Pacific. DNA sequence for portions of two mitochondrial genes, the large ribosomal subunit and cytochrome oxidase 1 was obtained from 16 species of sea cucumbers, including nine members of the family Cucumariidae. As reported for many mitochondrial genomes, a strong bias against G was noted in the coding strand at synonymous sites. In order to verify trees recovered in the presence of this bias, parsimony, maximum likelihood, distance, and log determinant methods were all employed. The resulting molecular phylogeny of the Cucumariidae, with a few exceptions, supported existing taxonomy which is based largely on the morphology of calcareous parts. In particular, evolutionary relationships among the brooding species were clarified. Our results confirm that C. pseudocurata Deichmann is distinct from C. curata Cowles and that these two species do not represent geographic variants of a single species. In fact C. pseudocurata appears to be conspecific with the more northerly distributed C. vegae Theel. We also clarify the identity of C. lubrica Clark and further suggest that C. fisheri astigmata (recently revised to Pseudocnus) should be considered a junior synonym of C. lubrica. The recent description of C. pallida Kirkendale and Lambert as a species, distinct from C. miniata (Brandt), is also supported. The resultant phylogenetic trees are consistent with multiple origins of direct development within the Cucumariidae. Finally, we suggest that an in-depth phylogenetic analysis of sea cucumber families will require examination of additional, more slowly evolving, regions of the genome(s).

Amino Acid Sequence↗
PubMed1996

Effects of scopolamine on learning and memory in monkeys.

The effects of scopolamine were evaluated in monkeys responding under operant procedures designed to evaluate drug effects on learning and memory. In one procedure, responding was maintained by food presentation under a multiple schedule. One component of the multiple schedule was a repeated-acquisition task in which the discriminative stimuli for left- and right-key responses changed each session (learning). In the other component, the discriminative stimuli for responses were the same each session (performance). In both components of the multiple schedule, scopolamine produced dose-related decreases in responding; there was little evidence of differential rate-decreasing effects between components. Percent errors in learning were increased in a dose-related manner, whereas percent errors in performance were generally unaffected except at high doses, which also produced substantial decreases in response rate. These results suggest that acquisition is more sensitive to the disruptive effects of scopolamine than is performance. The second procedure utilized repeated acquisition and delayed performance as a technique to study the effects of scopolamine on memory. In this procedure, each session was divided into three phases: acquisition, delay and performance. After a 24-h delay, scopolamine had little or no effect on retention, accuracy or rate of responding. In contrast, after a 60-min delay, scopolamine decreased retention in a dose-related manner. These data suggest that scopolamine produces a greater disruptive effect on short (60-min) versus long (24-h) delays.

Animals↗
PubMed1996

Treatment and prognosis of primary malignant small bowel tumors.

Primary malignant tumors of the small bowel are a heterogeneous group of tumors and are uncommon compared to tumors in other locations of the gastrointestinal tract. These tumors have been traditionally associated with a poor prognosis. The charts of 53 patients with primary malignant small bowel tumors at major Eastern Virginia Medical School teaching hospitals were retrospectively reviewed. Patient characteristics and presenting symptoms and signs were nonspecific. No single radiographic or endoscopic procedure was performed on every patient, and the diagnosis was suspected preoperatively in only 50 per cent of the patients. Tumors were most common in the ileum, and the most common histologic types were adenocarcinoma (53 per cent) and carcinoid (32 per cent). In univariate analysis, factors determining survival included histologic type, location of tumor, and stage. There was also a trend toward worse survival in patients receiving chemotherapy or radiation therapy, possibly due to patient selection factors. In multivariate analysis, only histology and stage significantly influenced survival. The overall 10-year survival of the entire group was 44 per cent. Small bowel tumors have a variable prognosis. A high index of suspicion and more frequent use of enteroclysis may lead to earlier detection and improved survival.

Actuarial Analysis↗
PubMed1995

Complete sequence (20 kilobases) of the polyprotein-encoding gene 1 of transmissible gastroenteritis virus.

The entire nucleotide sequence of cloned cDNAs containing the 5'-untranslated region and gene 1 of Purdue-115 strain of transmissible gastroenteritis virus (TGEV) was determined. This completes the sequence of the TGEV genome, which is 28,579 nucleotides long. The gene 1 is composed of two large open reading frames, ORF1a and ORF1b, which contain 4017 and 2698 codons, respectively (stop excluded). A brief, three-codon-long ORF is present upstream of ORF1a. ORF1b overlaps ORF1a by 43 bases in the (-1) reading frame. In vitro experiments indicated that translation of the ORF1a/b polyprotein involves an efficient ribosomal frameshifting activity, as previously shown for other coronaviruses. Analysis of the predicted ORF1a and ORF1b translation products revealed that the putative functional domains identified in infectious bronchitis virus (IBV), mouse hepatitis virus (MHV) and human coronavirus 229E (HCV 229E) are all present in TGEV. The amino-terminal half of the ORF1a product exhibits greater divergence than the carboxyl-terminal half, including within the TGEV/HCV229E pair. The ORF1b protein is overall highly conserved among the above four coronaviruses, except a divergent region situated near the carboxy terminus.

Amino Acid Sequence↗
PubMed1995

Angiosarcoma of the breast. Initial misdiagnosis is still common.

Primary angiosarcoma of the breast is a rare and often misdiagnosed disease. The most common clinical presentation is a painless mass in the affected breast, but the often varied presentation and the high incidence of histologic misdiagnosis make early detection rare. The tumor size and the histologic type correlate with the prognosis. The treatment for angiosarcoma of the breast is early and complete surgical excision of the mass with adequate margins. Axillary dissection is not indicated because the predilection for nodal metastasis is rare. The definitive role of adjuvant therapy remains undetermined. Chemotherapy and radiotherapy may play an important role in survival; however, the data are inconclusive. A high index of suspicion for angiosarcoma is a crucial tool in its proper diagnosis and treatment. It should always be noted that a vascular lesion that is associated with any breast mass is an angiosarcoma until proven otherwise.

Adult↗