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Biomedical subjects

L Thomas

Publications and source records attributed to L Thomas.

At least 271 records · Page 15Linked to original sources

Selective expression of PNA-binding glycoconjugates by invasive human melanomas: a new marker of metastatic potential.

Alterations of cell-surface glycoconjugates have been associated with invasiveness and metastatic capacity in a number of experimental and human tumors (bladder and colon cancer). We have recently shown that human melanoma cells from variants selected for high metastatic potential in an animal model bind the lectin peanut agglutinin (PNA), and that human melanoma cell populations enriched for PNA binding cells generated a higher frequency of metastases when xenografted into immune suppressed neonatal rats. We have therefore sought cells binding PNA in biopsied human melanocytic tumors and compared frequencies of PNA binding by cells from benign nevi, early and late primary melanomas, and metastatic melanomas. Sections of conventionally processed tissues were deparaffinised and exposed to biotinylated PNA; PNA fixation was revealed by the avidine/peroxidase/AEC technique. In 51 specimens tested, PNA appears to react electively with invasive tumors, since only one of the 7 early primary melanomas (Clark I-II) reacted while 13/23 late primary melanomas (Clark III-V), and 4/21 melanoma metastases were reactive. In addition, only 1/17 benign nevi bound PNA. In primary tumors, the reactive cells were exclusively invasive tumors cells in the dermis. PNA reactive material was observed in the cytoplasm and plasma membrane of reactive cells. Hence, alterations in composition and cellular localisation of glycoconjugates detectable by lectin histochemistry in melanoma cells may be markers of metastatic potential that may be applicable on an individual patient basis.

Animals↗

Variable detection of myeloid antigens in childhood acute lymphoblastic leukaemia.

AIMS: To determine whether the use of different sources of anti-CD13 and anti-CD33 monoclonal antibodies leads to discrepant results in childhood acute lymphoblastic leukaemia (ALL), which might contribute to the wide variation in the reported incidence of myeloid antigen expressing ALL in childhood. METHODS: Stored leukaemic cells from 10 children with previously defined myeloid positive ALL were examined. A range of commercially available anti-CD13 and anti-CD33 monoclonal antibodies, directly conjugated with phycoerythrin or fluorescein isothyocyanate, or both, was used. Positively reacting cells were detected by flow cytometry. RESULTS: There was a noticeable discordance between the different commercial sources of antibody and between the two fluorochromes in their ability to detect myeloid antigens, as well as variation in the intensity of staining. For CD13, one antibody reacted with eight cases and another with only four. Similarly, CD33 was detected in all 10 cases by one antibody and in only three by another. CONCLUSIONS: The lack of any consistent pattern of results suggests that various commercial antibodies against the same CD antigen might recognise different epitopes and that the number of molecules per cell might vary from case to case. These observations partly explain the variation in reported incidence and the failure to establish the clinical importance of myeloid positivity, and they highlight the importance of standardisation in multicentre studies in which immunophenotypic data are collected.

Antibodies, Monoclonal↗

Cyclosporin A has divergent effects on plasma LDL cholesterol (LDL-C) and lipoprotein(a) [Lp(a)] levels in renal transplant recipients. Evidence for renal involvement in the maintenance of LDL-C and the elevation of Lp(a) concentrations in hemodialysis patients.

Cardiovascular disease is the major cause of mortality in renal transplant recipients. Plasma levels of low-density lipoprotein cholesterol (LDL-C) are often elevated following renal transplantation, and the immunosuppressant cyclosporin A has been implicated as a predisposing factor for posttransplantation hyperlipidemia. Lipoprotein(a) [Lp(a)] is an LDL-like lipoprotein particle; elevated levels of Lp(a) provide an independent and significant risk factor for cardiovascular disease. Plasma concentrations of Lp(a) vary greatly among individuals, and the mechanisms that govern changes in their levels in transplant patients are unknown. The effect(s) of cyclosporin A on Lp(a) was studied in two groups of renal transplantation patients. In group I plasma lipoproteins including Lp(a) were measured before and after successful renal transplantation; this group received both prednisone and cyclosporin A for immunosuppression. Group II patients were studied after renal transplantation and received prednisone alone for immunosuppression. Following surgery, group I patients demonstrated increased plasma concentrations of LDL-C (mean +/- SEM range, 111 +/- 6 to 142 +/- 17 mg/dL; P < .005). In contrast, plasma Lp(a) levels for this group were markedly decreased after renal transplantation (median, 34.3 to 19.7 mg/dL). Patients not treated with cyclosporin A (group II) exhibited mean LDL-C and median Lp(a) levels (118 +/- 42 and 33.1 mg/dL, respectively) that were remarkably similar to those observed before renal transplantation (group I). These data confirm that hyperlipidemia following renal transplantation is associated with cyclosporin A therapy and show that this drug has opposing effects on plasma Lp(a) and LDL-C accumulations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Ineffective hip rotation with Pavlik harness. Prospective study of 35 infant dislocations.

35 hips in 31 infants diagnosed as unstable were treated with a Pavlik harness and followed by weekly clinical and monthly ultrasound evaluation to determine eventual stability. 26 hips became stable within 3 months, and 9 dislocations required reduction with hip spica placement; 1 of these subsequently required open reduction. Of the 7 infants with 9 hips that failed, 2 children had a late onset of treatment, 2 children had problems with brace fit or family acceptance, and 3 other children had no problem with use of the orthosis. Internal rotation of a degree not possible with the Pavlik harness was required to reduce 4 of these 9 hips. The Pavlik harness is ineffective in some patients because of the need for internal rotation.

Arthrography↗

[Pachydermoperiostosis. An ultrastructural study].

BACKGROUND: Pachydermoperiostosis (PDP) is a rare genetically determined disease belonging to the group of hypertrophic osteoarthropathies. Its aetiopathogenesis remains unclear. Most hypotheses favour an exogenous stimulation of fibroblasts. METHODS: A clinically typical patient with PDP was studied by electron microscopy with particular reference to the dermis and its cellular constituents. Fibroblasts from involved skin were cultured and studied in comparison with control cells. RESULTS: Remarkable modifications of the structure of the dermis were observed, encompassing irregular caliber of collagen fibres, extracellular deposits of microfibrils and of amorphous granular substance corresponding to the Alcian blue positive deposits seen by conventional histochemistry. The in vitro growth of fibroblasts was normal. CONCLUSION: Authors reviewed aetiopathogenic hypotheses. Our data suggest a genetically determined alteration of extracellular matrix production by fibroblasts as a possible explanation for the development of PDP.

Adult↗

[Perianal basal cell carcinoma. Apropos of 2 cases].

INTRODUCTION: Two cases of perianal basal cell carcinoma were reported. Less than 100 cases have been so far described. OBSERVATIONS: The first case was a pigmented tumour, in the second an erosive erythematous plaque somewhat similar to Paget's disease. COMMENTS: Basal cell carcinoma of the anal margin is about 15-fold less common than squamous cell carcinoma. The tumour is often ulcerated, sometimes infiltrative but metastasis never occurs. Histopathological findings are often close to what is observed in cloacogenic carcinoma. Surgical resection of the lesion is the best treatment but electrontherapy permitted lesion healing in one of our cases.

Aged↗

[Tufted folliculitis of the scalp].

INTRODUCTION: Tufted hair folliculitis is a localized scarring bacterial folliculitis due to Staphylococcus aureus. We present two cases. OBSERVATIONS: Both patients were in their thirties. The first had had an inflammatory sclerous lesion of the vertex for three years, and the second an alopecial scarring lesion. Clinically there were tufts of hair within or around the lesions. Staphylococcus aureus was found in biopsy samples which showed hairs or composed follicles. Prolonged treatment with oral antibiotics led to progressive limitation of the lesions. DISCUSSION: Tufted hair folliculitis is a characteristic folliculitis of the scalp showing scar formation and the presence of Staphylococcus aureus. The review of the literature raises the question of the role of local immunity and the nature of the hair tufts: primary anomaly or secondary to Staphylococcus infection? The therapeutic attitude is not well defined but prolonged treatment with oral antibiotics can stabilize the lesions.

Adult↗

[A case of unilateral elastosis with cysts and comedones. Favre-Racouchot syndrome].

INTRODUCTION: Cutaneous elastosis with cysts and comedones (Favre-Racouchot) is one of the oldest known manifestations of helioderma. Both sides of the face are usually involved symmetrically. CASE REPORT: We observed a 65-year-old woman with extremely severe Favre-Racouchot disease localized exclusively on the left side of the face. The diagnosis of elastosis with cysts and comedones was confirmed histologically. This elastosis with cysts and comedones was associated with spasms of the hemiface treated with injections of botulinic toxin. This association was fortuitous and we retained actinic irradiation as the causal agent in this woman who had worked for 15 years in the same room. The elastosis occurred on the side of the face which had been continuously exposed at the same orientation to the window. COMMENTS: This original observation is similar to cases where facial exposure to artificial light or sunlight is asymmetrical, leading to a higher incidence of lesions on one side of the face: colloid milium, actinic keratosis, Dubreuilh melanoma (malignant lentigo) or simple helioderma. The asymmetrical nature of the actinic lesions is often related to automobile driving. This case was particular since it demonstrated that Favre-Racouchot elastosis with cysts and comedones is due to actinic irradiation and not to skin aging.

Acne Vulgaris↗

[Abdominopelvic radiation therapy in the treatment of ovarian carcinoma. Study of a continuous series of 167 patients].

From May 1981 through December 1990, 167 patients with ovarian carcinoma were treated with whole abdominal irradiation. All patients of the first group (n = 62) presented with no or minimal (< 2 cm) residual disease at the time of irradiation. They received whole abdominal irradiation after initial surgery. Residual disease was left after initial surgery for patients of the second group (n = 105). They underwent a cisplatin polychemotherapy regimen followed by second-look laparotomy and abdominopelvic irradiation. The irradiation was performed by a four orthogonal field's technique. Thirty grays were given with a 25 MV photon beam. Boosts were performed in 50 cases (mean dose of 15 Gy); 91% have completed irradiation at the prescribed dose level; 5% had severe intestinal toxicity requiring surgery. The median follow-up was 68 months. The 5-year actuarial survival rate was 50%, 67% group 1.40% group 2. Five-year actuarial survival was 84% for T1, 61.5% for T2, 38% for T3. Five-year survival depended on tumor rest after initial surgery (residual disease 36.5%, no residual disease 70%). For patients in group 2, the size of residual disease at second-look laparotomy was a significant prognostic factor: five-year actuarial survival 76% with negative second-look, microscopic residual disease (positive cytology or random biopsies) 60%, microscopic disease after cytoreductive surgery at second-look 22%, macroscopic residual disease (small nodules) 10%. These results indicate that abdominopelvic irradiation is valuable in the treatment of ovarian carcinoma when there is no macroscopic residual disease after initial surgery or second look laparotomy. To assess the place of radiotherapy, randomized trials comparing whole abdominal irradiation with chemotherapy, watch policy for staged patients is warranted.

Actuarial Analysis↗

Inhibition of HIV-1 gp160-dependent membrane fusion by a furin-directed alpha 1-antitrypsin variant.

Furin is a membrane-associated calcium-dependent serine endoprotease that cleaves proproteins on the carboxyl side of the consensus sequence -Arg-X-Lys/Arg-Arg-. Using site-directed mutagenesis, a variant alpha 1-antitrypsin (alpha 1-AT) was constructed which contains in its reactive site -Arg-X-X-Arg-, the minimal sequence required for efficient processing by furin (Molloy, S. S., Bresnahan, P. A., Leppla, S. H., Klimpel, K. R., and Thomas, G. (1992) J. Biol. Chem. 267, 16396-16402). This alpha 1-AT variant, [Arg355 Arg358]alpha 1-AT (alpha 1-PDX), is greater than 3,000-fold more effective than [Arg358]alpha 1-AT (alpha 1-AT Pittsburgh, alpha 1-PIT) at inhibiting furin in vitro (K0.5 = 0.03 microgram/ml). Furthermore, the P4 Arg in alpha 1-PDX greatly attenuates the thrombin inhibitory properties of this serpin (> 300-fold) compared with alpha 1-PIT (which contains a P4 Ala), thus increasing the selectivity of alpha 1-PDX for furin. Expression studies show that alpha 1-PDX, and not alpha 1-PIT, blocks the processing of two furin substrates, pro-beta-nerve growth factor and human immunodeficiency virus (HIV)-1 gp160 in transfected cells. In addition, a syncytium assay shows that alpha 1-PDX blocks the membrane fusogenic properties of HIV-1 gp160. The potential use of alpha 1-PDX in manipulating the activation of proproteins in a tissue- and time-specific manner is discussed.

Amino Acid Sequence↗

Mapping of residues forming the voltage sensor of the voltage-dependent anion-selective channel.

Voltage-gated ion-channel proteins contain "voltage-sensing" domains that drive the conformational transitions between open and closed states in response to changes in transmembrane voltage. We have used site-directed mutagenesis to identify residues affecting the voltage sensitivity of a mitochondrial channel, the voltage-dependent anion-selective channel (VDAC). Although charge changes at many sites had no effect, at other sites substitutions that increased positive charge also increased the steepness of voltage dependence and substitutions that decreased positive charge decreased voltage dependence by an appropriate amount. In contrast to the plasma membrane K+ and Na+ channels, these residues are distributed over large parts of the VDAC protein. These results have been used to define the conformational transitions that accompany voltage gating of an ion channel. This gating mechanism requires the movement of large portions of the VDAC protein through the membrane.

Amino Acid Sequence↗

Genomic instability occurs in colorectal carcinomas but not in adenomas.

Genomic instability, as demonstrated by the presence of additional alleles at short tandemly repeated (STR) loci, has recently been observed in colorectal tumours from individuals with hereditary nonpolyposis colorectal cancer (HNPCC), and in some sporadic tumours. These neoplasms have been called replication error positive (RER+). In this study, we confirm the presence of genomic instability in a proportion of unselected colorectal carcinomas but find no evidence of instability in adenomas. We further report replication errors in a tetranucleotide sequence, and in STRs within two tumour suppressor genes. 108 colorectal adenocarcinomas and 46 adenomas were analysed for the presence of variant bands at 4-15 microsatellite markers. Seven (6.5%) of carcinomas were RER+, four of which originated from the proximal colon. Analysis of the adenomas and of matched adenoma-carcinoma and carcinoma-metastatic samples from four patients suggests that the replication errors may occur during the development of carcinomas but are rare in adenomas.

Adenocarcinoma↗

A nurse practitioner intervention to increase breast and cervical cancer screening for poor, elderly black women. The Harlem Study Team.

OBJECTIVE: To compare nurse practitioner (NP) and physician rates of breast and cervical cancer screening among poor, elderly black women. DESIGN: A quasi-experimental design was used to compare pre- and postintervention annual screening rates. Rates were determined by medical record audits. SETTING: Two urban public hospital primary care clinics served as the study sites. PATIENTS: All women aged 65 years or more were eligible to participate. INTERVENTIONS: Women were offered screening by a NP during a routine visit in the intervention site; a physician reminder system was used in the control site. MAIN RESULTS: Baseline annual screening rates were comparable in the two study sites. At the end of the study period, rates were significantly higher in the NP site, compared with the control. In the NP clinic, the annual rate of Pap tests increased to 56.9% from the baseline of 17.8%, and mammographies increased to 40% from 18.3%. In comparison, rates remained low in the control site, increasing only to 18.2% of women receiving Pap tests from a baseline of 11.8%, and remaining at 18% for mammography. CONCLUSIONS: Use of a NP to deliver same-day screening is an effective strategy to target poor, elderly black women for breast and cervical cancer screening. However, even with the substantial increases in rates obtained with the NP intervention, screening in this vulnerable population remains below nationally targeted levels.

Black or African American↗