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Biomedical subjects

L F Brown

Publications and source records attributed to L F Brown.

At least 73 records · Page 4Linked to original sources
PubMed1995

Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer.

Solid tumors must induce a vascular stroma to grow beyond a minimal size, and the intensity of the angiogenic response has been correlated with prognosis in breast cancer patients. Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a secreted protein that has been implicated in tumor-associated angiogenesis. Vascular permeability factor directly stimulates endothelial cell growth and also increases microvascular permeability, leading to the extravasation of plasma proteins, which alter the extracellular matrix in a manner that promotes angiogenesis. To determine whether VPF has a role in breast cancer, we used in situ hybridization to study VPF mRNA expression in normal breast tissue (13 specimens), comedo-type ductal carcinoma in situ (DCIS) (four specimens), infiltrating ductal carcinoma (12 specimens), infiltrating lobular carcinoma (two specimens), metastatic ductal carcinoma (three specimens) and metastatic lobular carcinoma (one specimen). Vascular permeability factor mRNA was expressed at a low level by normal duct epithelium but was expressed at high levels in tumor cells in all cases of comedo-type DCIS, infiltrating ductal carcinoma, and metastatic ductal carcinoma. In contrast, VPF mRNA was not expressed at high levels in infiltrating lobular carcinoma. We also used in situ hybridization to study the expression of two recently described endothelial cell surface VPF receptors, flt-1 and kdr. Vascular permeability factor receptor mRNA was strongly expressed in endothelial cells of small vessels adjacent to malignant tumor cells in DCIS, infiltrating ductal carcinoma, and metastatic ductal carcinoma. In contrast, no definite labeling for receptor mRNA was detected in infiltrating lobular carcinoma or nonmalignant breast tissue. The intense expression of VPF mRNA by breast carcinoma cells and of VPF receptor mRNA by endothelial cells of adjacent small blood vessels provides strong evidence linking VPF expression to the angiogenesis associated with comedo-type DCIS, infiltrating ductal, and metastatic ductal breast carcinoma.

Breast Neoplasms↗
PubMed1995

Vascular permeability factor (vascular endothelial growth factor) is strongly expressed in the normal male genital tract and is present in substantial quantities in semen.

PURPOSE: Vascular permeability factor (VPF) is a potent inducer of microvascular hyperpermeability and stimulates endothelial cell growth and angiogenesis. This study examines expression of VPF in the male genital tract. MATERIALS AND METHODS: Vascular permeability factor in seminal plasma was quantified by immunoassay. Vascular permeability factor mRNA and protein expression in tissue were studied by situ hybridization and immunohistochemistry. RESULTS: All seminal plasmas studied contained high levels of VPF. Prostatic and seminal vesicle epithelium labeled strongly for VPF mRNA and protein. CONCLUSIONS: The strong expression of VPF in prostate and seminal vesicle and the high concentration of VPF in semen suggest an important role for this cytokine in male fertility.

Adult↗
PubMed1995

Keratinocyte-derived vascular permeability factor (vascular endothelial growth factor) is a potent mitogen for dermal microvascular endothelial cells.

Expression of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is markedly increased in the epidermis of lesional psoriatic skin and in healing skin wounds. In this study, we characterized the effects of several cytokines and growth factors on the expression and secretion of VPF/VEGF mRNA and protein by cultured human epidermal keratinocytes, as well as the effect of VPF/VEGF on the growth of cultured human dermal microvascular endothelial cells. Transforming growth factor-alpha, epidermal growth factor, and phorbol myristate acetate markedly stimulated VPF/VEGF mRNA expression by cultured keratinocytes; as in psoriatic skin, the three most common VPF/VEGF isoforms (encoding proteins of 121, 165, and 189 amino acids) were upregulated to an equal extent. Transforming growth factor (TGF)-alpha, epidermal growth factor, and phorbol myristate acetate also enhanced the secretion of VPF/VEGF by keratinocytes; in contrast, a number of other cytokines including interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor-alpha, interferon-gamma, and transforming growth factor-beta did not induce VPF/VEGF secretion. The VPF/VEGF secreted by keratinocytes was biologically active in that, like recombinant human VPF/VEGF, it potently stimulated dermal endothelial cell proliferation. Scatchard analysis revealed two high-affinity VPF/VEGF binding sites on dermal endothelial cells with dissociation constants of 51 pM and 2.9 pM. These results suggest that the avascular epidermis has the capacity to regulate dermal angiogenesis and microvascular permeability by a paracrine mechanism involving the secretion of VPF/VEGF. Similar mechanisms may be anticipated in a variety of inflammatory and neoplastic skin diseases characterized by microvascular hyperpermeability, edema, and angiogenesis.

Binding Sites↗
PubMed1995

Increased expression of vascular permeability factor (vascular endothelial growth factor) in bullous pemphigoid, dermatitis herpetiformis, and erythema multiforme.

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), plays an important role in the increased vascular permeability and angiogenesis associated with many malignant tumors. In addition, VPF/VEGF is strongly expressed by epidermal keratinocytes in wound healing and psoriasis, disorders that are also characterized by increased microvascular permeability and angiogenesis. In this study, we investigated the expression of VPF/VEGF in three bullous diseases with subepidermal blister formation that are characterized by hyperpermeable dermal microvessels and pronounced papillary dermal edema. The expression of VPF/VEGF mRNA was strongly up-regulated in the lesional epidermis of bullous pemphigoid (n = 3), erythema multiforme (n = 3), and dermatitis herpetiformis (n = 4) as detected by in situ hybridization. Epidermal labeling was particularly intense over blisters, but strong expression was also noted in areas of the epidermis adjacent to dermal inflammatory infiltrates at a distance from blisters. Moreover, the VPF/VEGF receptors, flt-1 and KDR, were up-regulated in endothelial cells in superficial dermal microvessels. High levels of VPF/VEGF (138-238 pM) were detected in blister fluids obtained from five patients with bullous pemphigoid. Addition of blister fluid to human dermal microvascular endothelial cells exerted a dose-dependent mitogenic effect that was suppressed after depletion of VPF/VEGF by immunoadsorption. These findings strongly suggest that VPF/VEGF plays an important role in the induction of increased microvascular permeability in bullous diseases, leading to papillary edema and fibrin deposition and contributing to the bulla formation characteristic of these disorders.

Adult↗
PubMed1995

Balloon catheterization induced arterial expression of embryonic fibronectins.

Fibronectins (FNs) comprise a family of adhesive extracellular matrix proteins that arise by alternative splicing in three regions: V (IIICS), EIIIA (ED-A), and EIIIB (ED-B). FNs bearing the EIIIA and EIIIB segments are prevalent during embryogenesis, expressed to lesser degrees in normal adult tissues, and may be locally reexpressed at adult tissue injury. RNase mapping shows that normal rat arteries express low levels of FNs that are predominantly EIIIA- and EIIIB-. Following balloon injury, arterial walls produce increased total levels of FN transcripts that preferentially include both the EIIIA and EIIIB segments. However, despite inducing increased total FN mRNA, balloon injury does not alter the relative composition of V120+, V95+, AND V0 spliced forms. In situ hybridization reveals that as early as 4 days after injury medial cells express increased total FN mRNA, and by 7 days substantial neointimal and focal medial synthesis of EIIIA+, EIIIB+, and V120+ FNs occurs; macrophages do not significantly contribute to this observed vascular FN synthesis. Consistent with the mRNA data, immunofluorescence microscopic analysis reveals increased deposition of EIIIB+ and V+ FN protein forms in injured arterial walls, particularly within the neointima. Our results suggest that local synthesis of specific FN isoforms is important to the neointimal formation that ensues after balloon injury.

Alternative Splicing↗
PubMed1995

Expression of vascular permeability factor/vascular endothelial growth factor by human granulosa and theca lutein cells. Role in corpus luteum development.

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is a cytokine that is overexpressed in many tumors, in healing wounds, and in rheumatoid arthritis. VPF/VEGF is thought to induce angiogenesis and accompanying connective tissue stroma in two ways: 1), by increasing microvascular permeability, thereby modifying the extracellular matrix and 2), as an endothelial cell mitogen. VPF/VEGF has been reported in animal corpora lutea and we investigated the possibility that it might be present in human ovaries and have a role in corpus luteum formation. We here report that VPF/VEGF mRNA and protein are expressed by human ovarian granulosa and theca cells late in follicle development and, subsequent to ovulation, by granulosa and theca lutein cells. Therefore, VPF/VEGF is ideally positioned to provoke the increased permeability of thecal blood vessels that occurs shortly before ovulation. VPF/VEGF likely also contributes to the angiogenesis and connective tissue stroma generation that accompany corpus luteum/corpus albicans formation. Finally, VPF/VEGF was overexpressed in the hyperthecotic ovarian stroma of Stein-Leventhal syndrome in which it may also have a pathophysiological role.

Adolescent↗
PubMed1995

Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis.

VPF/VEGF is a multifunctional cytokine that contributes to angiogenesis by both direct and indirect mechanisms. On the one hand, VPF/VEGF stimulates the ECs lining nearby microvessels to proliferate, to migrate, and to alter their pattern of gene expression. On the other hand, VPF/VEGF renders these same microvascular ECs hyperpermeable so that they spill plasma proteins into the extravascular space, leading to the clotting of extravasated fibrinogen with deposition of a fibrin gel. Extravascular fibrin serves as a provisional matrix that favors and supports the ingrowth of new blood vessels and other mesenchymal cells that generate mature, vascularized stroma. These same principles apply in tumors, in several examples of non-neoplastic pathology, and in physiological processes that involve angiogenesis and new stroma generation. In all of these examples, microvascular hyperpermeability and the introduction of a provisional, plasma-derived matrix precede and accompany the onset of EC division and new blood vessel formation. It would seem, therefore, that tumors have "borrowed" fundamental mechanisms that developed in multicellular organisms for purposes of tissue defense, renewal, and repair. VPF/VEGF, therefore has taught us something new about angiogenesis; namely, that vascular hyperpermeability and consequent plasma protein extravasation are important, perhaps essential, elements in its generation. However, this finding raises a paradox. While VPF/VEGF induces vascular hyperpermeability, other potent angiogenic factors apparently do not, at least in subtoxic concentrations that are more than sufficient to induce angiogenesis. Nonetheless, wherever angiogenesis has been studied, the newly generated vessels have been found to be hyperpermeable. How, therefore, do angiogenic factors other than VPF/VEGF lead to the formation of new and leaky blood vessels? We do not as yet have a complete answer to this question. One possibility is that at least some angiogenic factors mediate their effect by inducing or stimulating the expression of VPF/VEGF. In fact, there is already one clear example of this. TGF-alpha is a potent angiogenic factor but does not itself increase microvascular permeability. However, TGF-alpha strikingly upregulates VPF/VEGF expression in cultured keratinocytes and is thought to be responsible, at least in part, for the overexpression of VPF/VEGF in psoriasis. Moreover, overexpression of TGF-alpha, along with that of the EGF receptor with which it interacts, is characteristic of many malignant tumors, raising the possibility that TGF-alpha acts to stimulate VPF/VEGF expression in other types of epithelial cells and in this manner induces angiogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

A comparison of methods of ranking the provision of periodontal services by dental practices in south Australia.

Wide variations documented in the provision of periodontal services have raised concerns about possible under- and over-servicing. The aim of this study was to compare various methods used to measure the provision of periodontal services. The methods compared were procedure logs to measure service mix, audits of patients' records and patients' recall of treatment received at their last series of dental visits. The study was conducted among private general dental practices in Adelaide, South Australia. The first aspect of the study compared 2,290 patients' recall of receiving periodontal information, including oral hygiene instruction, or periodontal treatment at their last dental visit(s) with notations of their dental records. Discordance was high, with disagreement occurring in 71.5 per cent of cases for patient education, and 42.2 per cent of cases for periodontal treatment. Comparison of the ranking of the provision of periodontally-related services by 24 dental practices according to the three data collection methods showed that the ranking of a practice was significantly related to the data collection method used (Friedman's two-way ANOVA; P < 0.05). It was concluded that methods used to measure the provision of periodontal care are fallible, and that more than one method may be needed to record the full range of preventive and treatment services.

Analysis of Variance↗
PubMed1995

Identification of a novel gene, selectively up-regulated in human carcinomas, using the differential display technique.

Using the differential display technique, selecting for genes up-regulated in renal cell carcinoma compared with normal renal parenchyma, we isolated a novel gene, designated DD96. As determined by in situ and Northern blot hybridization studies, DD96 is expressed only in rare normal epithelial cell populations, such as the proximal tubular epithelial cells of the kidney. However, it is expressed diffusely in malignant epithelial cells of the wide majority of renal cell carcinomas. In addition, DD96 is overexpressed markedly in various human carcinomas originating from the colon, breast, and lung, as well as in a number of cell lines derived from tumors of these organs compared with normal epithelial cell populations. Furthermore, the expression of DD96 is induced in immortalized breast ductal epithelial cell lines compared with normal breast ductal epithelial cells, and, in vivo, in premalignant conditions, such as adenoma of the colon and ductal carcinoma in situ of the breast. Sequence analysis of a complete cDNA clone isolated from a human kidney cDNA library revealed that DD96 encodes for a protein of approximately Mr 13,500. These results suggest that DD96 may play a role in the early events associated with malignant transformation; however, its function remains to be determined.

Amino Acid Sequence↗
PubMed1994

Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis.

Psoriatic skin is characterized by microvascular hyperpermeability and angioproliferation, but the mechanisms responsible are unknown. We report here that the hyperplastic epidermis of psoriatic skin expresses strikingly increased amounts of vascular permeability factor (VPF; vascular endothelial growth factor), a selective endothelial cell mitogen that enhances microvascular permeability. Moreover, two VPF receptors, kdr and flt-1, are overexpressed by papillary dermal microvascular endothelial cells. Transforming growth factor alpha (TGF-alpha), a cytokine that is also overexpressed in psoriatic epidermis, induced VPF gene expression by cultured epidermal keratinocytes. VPF secreted by TGF-alpha-stimulated keratinocytes was bioactive, as demonstrated by its mitogenic effect on dermal microvascular endothelial cells in vitro. Together, these findings suggest that TGF-alpha regulates VPF expression in psoriasis by an autocrine mechanism, leading to vascular hyperpermeability and angiogenesis. Similar mechanisms may operate in tumors and in healing skin wounds which also commonly express both VPF and TGF-alpha.

Base Sequence↗
PubMed1994

Vascular permeability factor/endothelial growth factor (VPF/VEGF): accumulation and expression in human synovial fluids and rheumatoid synovial tissue.

Vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF), is a potent microvascular permeability enhancing cytokine and a selective mitogen for endothelial cells. It has been implicated in tumor angiogenesis and ascites fluid accumulation. Since development of the destructive synovial pannus in rheumatoid arthritis (RA) is associated with changes in vascular permeability (synovial fluid accumulation), synovial cell hyperplasia, and angiogenesis, we examined synovial fluids (SFs) and joint tissue for the expression and local accumulation of VPF/VEGF. VPF/VEGF was detected in all of 21 synovial fluids examined and when measured by an immunofluorimetric assay, ranged from 6.9 to 180.5 pM. These levels are biologically significant, since < 1 pM VPF/VEGF can elicit responses from its target cells, endothelial cells. Levels of VPF/VEGF were highest in rheumatoid arthritis fluids (n = 10), with a mean value (+/- SEM) of 59.1 +/- 18.0 pM, vs. 21.4 +/- 2.3 pM for 11 SFs from patients with other forms of arthritis (p = 0.042). In situ hybridization studies that were performed on joint tissues from patients with active RA revealed that synovial lining macrophages strongly expressed VPF/VEGF mRNA, and that microvascular endothelial cells of nearby blood vessels strongly expressed mRNA for the VPF/VEGF receptors, flt-1 and KDR. Immunohistochemistry performed on inflamed rheumatoid synovial tissue revealed that the VPF/VEGF peptide was localized to macrophages within inflamed synovium, as well as to microvascular endothelium, its putative target in the tissue. Together, these findings indicate that VPF/VEGF may have an important role in the pathogenesis of RA.

Adult↗
PubMed1994

Service mix in general dental practices employing and not employing dental hygienists.

Service mix studies conducted in Australia have indicated a low provision of periodontal services. The service mix in Australian general dental practices employing dental hygienists has not been studied. This study compares the service mix between 18 practices employing hygienists and 29 practices not employing hygienists in Adelaide. Practices employing hygienists tended to be larger group practices, with younger dentists seeing a younger set of patients. Practices employing dental hygienists provided a mean of 97.9 services to 57.2 patients over 2 days, significantly higher than the mean of 68.8 procedures to 39.1 patients in practices not employing dental hygienists. Comparing the % of procedures provided in treatment categories as a ratio of total procedures, practices employing dental hygienists provided significantly more periodontal procedures and less oral surgery, prosthetic and restorative procedures. Periodontally-related services accounted for an average of 37.7% of procedures in practices employing dental hygienists compared with 18.9% in practices not employing dental hygienists (p < 0.05). Periodontal and preventive treatment of 50.7% of patients in practices employing hygienists was delegated to a hygienist, and the level of delegation of periodontally-related procedures was 77.2%. Over 90% of procedures performed by hygienists were periodontally-related, with the removal of subgingival calculus accounting for 57.7% of all procedures provided by dental hygienists. In conclusion, practices employing hygienists had a more periodontally-orientated service mix, with hygienists acting to complement the services of dentists in the provision of periodontal services, rather than as a substitute for the dentist.

Adult↗
PubMed1994

Evaluation of a continuing education intervention "Periodontics in General Practice".

Evidence exists that some dentists may be failing to perform adequate periodontal diagnostic and preventive care for their patients. Continuing education (CE) is an avenue that is frequently employed as a strategy to alter the style of practice. This paper presents an evaluation of a year-long continuing education intervention "Periodontics in General Practice", conducted among randomly selected private general dental practices in Adelaide, South Australia. The CE intervention featured a 1-day seminar, bi-monthly newsletters, individualised 3-monthly comparative feedback, and technical assistance. The study employed a longitudinal quasi-experimental design, which allowed for evaluation of the effectiveness of the intervention among practices employing hygienists (n = 12) and not employing dental hygienists (n = 12), taking into account the covariates of baseline level of provision of periodontal services, the practice's level of participation in the intervention and attendance at other CE courses in periodontics over the year. A comparison group of practice (n = 12) did not participate in the intervention over the year. Patient record audits, conducted at baseline and at 12 months, provided data for the evaluation of the effect of the intervention on the recording of periodontal diagnostic, preventive and treatment items. Practices participating in the intervention showed increases in the percentage of records containing at least one periodontal diagnostic notation, and those practices employing hygienists showed an increase in the percentage of records with at least one preventive notation and one treatment item.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Hygienist employment and the presence of periodontal notations in general dental practice patient records.

Available data suggest that the provision of periodontally related services in general dental practices is low. However, studies indicate that the employment of dental hygienists is associated with increased provision. One method of measuring is by examination of notations in patient treatment records. As part of a project assessing the effectiveness of professional education in changing the provision of periodontal services, 2280 records, comprising 60 randomly selected records of dentate adult patients who had received a dental examination in the previous 6 months were audited in each of 38 practices, 13 of which employed hygienists. Entries of a periodontal nature were classified under 3 categories: diagnostic, preventive and treatment. The presence or absence of each item on each record was recorded. Diagnostic services were notated infrequently overall, but practices employing hygienists had a significantly lower number of records with no diagnostic notations. Preventive items were more frequently notated in practices employing hygienists. Treatment items were most frequently notated in both types of practices. Overall, 13 of the 23 items were recorded significantly more frequently in practices employing hygienists.

Adult↗
PubMed1994

Research in dental health education and health promotion: a review of the literature.

This article presents a review of research in dental health education and health promotion. In the period 1982 to 1992, a total of 57 studies evaluating the effectiveness of interventions to alter individuals' behavior related to dental health were identified. Combining the results of these 57 studies with descriptive articles published over the same period, it appears that dental health education can result in improvements in objective measures of dental health behaviors and actual oral health measures, but has only limited success in changing attitudes towards dental issues and achieves only short-term gains in knowledge. The limited use of theoretical frameworks, poor statistical analyses, the use of convenient samples and the short post-intervention follow-up periods diminish the contribution of this research to the development of dental health policy and the formation of strategies to improve the health of communities.

Adolescent↗
PubMed1994

Ultrastructural immunogold localization of osteopontin in human gallbladder epithelial cells.

We used a post-embedding ultrastructural immunogold method to localize osteopontin in human gallbladder epithelial cells. This glycoprotein, originally described in bone but recently found to have a much wider distribution in many epithelia and in some mesenchymal cells, was present in the filamentous glycocalyx, small apical cytoplasmic smooth membrane-bound vesicles, large membrane-bound cytoplasmic granules, and in portions of the Golgi complex in gallbladder columnar epithelial cells. These findings suggest that newly synthesized osteopontin is packaged in Golgi-derived granules that release their contents by classical exocytosis from the cell surface. At least a portion of secreted osteopontin remains on the cell surface, where it becomes integrated into the filamentous glycocalyx coating the luminal surface of gallbladder epithelial cells.

Amino Acid Sequence↗
PubMed1994

Incidence of attachment loss in community-dwelling older adults.

Since 1985, only four studies have been published that present data on attachment loss in populations. The purpose of this study was to present the incidence of attachment loss over an 18-month period in a representative sample of community-dwelling older adults. In addition, the utility of multivariate prediction models to distinguish between people who will and will not experience disease progression was explored. The Piedmont 65+ Dental Study of the Elderly is a longitudinal investigation of a random sub-sample of over 1,000 community-dwelling people over the age of 65 in five contiguous North Carolina counties. The five dentists who conducted the in-home examinations and interviews at baseline also participated at 18 months and examined the same subjects. The overall attrition rate for blacks was 27% and the rate for whites was 23%. At 18-months, the baseline attachment level scores for those subjects who were lost from the study were not significantly different from the scores of those who remained in the study. A change in attachment loss of 3 mm or more over the 18 months was set as a conservative estimate of actual change taking place. Blacks were significantly more likely to experience attachment loss irrespective of the number of sites involved (P < .05). Approximately half the people had at least one losing site and about one-third of the blacks and one-fourth of the whites had at least two losing sites. A total of 24% of blacks and 16% of whites had 3 or more losing sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Black or African American↗