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Biomedical subjects

J Slavin

Publications and source records attributed to J Slavin.

54 records · Page 3Linked to original sources

Fibroblast growth factors: at the heart of angiogenesis.

Acidic fibroblast growth factor (FGF-1) and basic fibroblast growth factor (FGF-2) are ubiquitous cytokines found in many tissues. They have effects on multiple cell types derived from mesoderm and neuroectoderm, including endothelial cells. In this review the structure and function of the fibroblast growth factor family and its receptors are described. The evidence implicating both FGF-1 and FGF-2 in the control of blood vessel formation is presented and their involvement in normal and pathological angiogenesis during adult life is then described in more detail.

Adult↗

Whole grain intake and cancer: a review of the literature.

There has been little research concerning the health effects of whole grain intake in humans. We have synthesized 15 american and European case-control and prospective studies of whole grain intake. Most subjects were middle aged or older. The studies employed disparate dietary methods, and the foods referred to and quantities eaten are ill defined. Nevertheless there is a striking consistency in reduced risk for colorectal and gastric cancers associated with intake of whole grain, also found in isolated studies of endometrial cancer and coronary heart disease. Because reduced risk was not associated with refined grain intake, these findings do not appear to be confounded by participant confusion concerning refined vs. whole grains. The independence of these findings from reduced risk associated with fruit and vegetable intake is not established. There should be further research to establish whether whole grain intake is protective against chronic disease.

Colorectal Neoplasms↗

Primary vulvar sarcomas.

Vulvar sarcomas are uncommon, comprising only approximately 2% of all vulvar malignancies. Consequently, most reported series contain only a few cases. We add to the literature 10 cases of various primary sarcomas of the vulva, including previously unreported cases of angiosarcoma and a neoplasm resembling Ewing's sarcoma. The only histologic feature helpful in determining prognosis was tumor necrosis.

Adult↗

Monocyte chemotactic protein-1 (MCP-1) mRNA is down-regulated in human dermal fibroblasts by dexamethasone: differential regulation by TGF-beta.

Macrophages are a source of cytokines driving repair. Wound macrophages are derived from circulating monocytes. Monocyte chemotactic protein-1 (MCP-1) is a potent specific monocyte chemoattractant. Treatment of serum stimulated dermal fibroblasts with dexamethasone led to a dose dependent down-regulation of MCP-1 mRNA levels. Such an anti-inflammatory effect may partially explain the negative influence of glucocorticoid treatment on wound repair. Topical or parenteral of fibroblasts cultured in serum free media with TGF-beta increased MCP-1 mRNA levels. TGF-beta treatment of fibroblasts cultured in serum also partially overcame the dexamethasone mediated decrease in MCP-1 mRNA levels. In glucocorticoid treated animals TGF-beta may stimulate repair by an indirect pro-inflammatory action following transcriptional up-regulation of MCP-1.

Anti-Inflammatory Agents↗

Transforming growth factor beta (TGF-beta) and dexamethasone have direct opposing effects on collagen metabolism in low passage human dermal fibroblasts in vitro.

Collagen metabolism is a balance between synthesis and lysis. Both are under tight regulatory control. TGF-beta reverse the impairment of healing seen after glucocorticoid treatment in vivo. Both TGF-beta and glucocorticoids are known to regulate collagen metabolism directly. We have examined the effect of dexamethasone and of TGF-beta individually and in combination on the regulation of procollagen type 1, interstitial collagenase and tissue inhibitor of metallo-proteinase-1 (TIMP-1) synthesis at both the protein and mRNA levels in low passage human dermal fibroblasts. Dexamethasone treatment decrease synthesis of procollagen and caused a dose dependent down-regulation of TIMP-1 synthesis. Interstitial collagenase synthesis by fibroblasts was detectable but low. Thus, glucocorticoid treatment of fibroblasts tilts the balance of collagen metabolism away from accumulation. TGF-beta had opposing effects, stimulating both procollagen and TIMP-1 synthesis at the protein and mRNA levels. TGF-beta was able to cause a dose-dependent reversal of the glucocorticoid induced decrease in procollagen and TIMP-1 synthesis. Stimulation of healing in glucocorticoid treated animals by TGF-beta may be by the direct action of this agent upon fibroblast collagen metabolism.

Blotting, Northern↗

The absence of HPV DNA in genital specimens from infants.

OBJECTIVE: To identify the prevalence of HPV DNA using the polymerase chain reaction (PCR) in neonatal foreskin and cervical specimens obtained at necropsy. MATERIALS: Foreskin and cervical specimens were obtained from consecutive neonates who had autopsies performed at The Royal Women's Hospital, Melbourne, from June 1991 to February 1992. Specimens were analysed for HPV DNA using the polymerase chain reaction and the L1 consensus primers and generic probes. RESULTS: Specimens were obtained from 98 neonates, 52 males and 46 female. The mean gestational age of the neonates was 29 weeks (range 20-42). Eighty neonates died in utero, three during labour and 15 following delivery. Ninety four were delivered vaginally whilst four were delivered by caesarean section. Samples were collected a mean of 20 hours (range 2-48) from the time of delivery. In 30 cases there was evidence of autolytic change while in the remaining cases, the histology was well preserved. No evidence of HPV DNA was found in any of the samples using the L1 general primers (95% confidence interval 0-3.6%). Recent cervical cytology was available on 70 of the infant's mothers. Six had cytological evidence of HPV infection while the remainder were normal. CONCLUSIONS: HPV DNA is uncommonly detected (by PCR) in foreskin and cervical specimens obtained from neonates.

Cervix Uteri↗

Thymic abscess with bacteremia and manubriosternal pyarthrosis in a geriatric patient.

We describe a geriatric patient with acute substernal chest pain thought to be due to coronary heart disease, who was subsequently found to have Staphylococcus aureus bacteremia associated with infection of the thymus and manubriosternal joint. To our knowledge, this is the first report of (1) a thymic abscess in a geriatric patient, (2) a thymic abscess associated with bacteremia, (3) extra-articular extension of manubriosternal pyarthrosis, and (4) manubriosternal pyarthrosis in the geriatric age group.

Abscess↗

Effect of transforming growth factor beta and basic fibroblast growth factor on steroid-impaired healing intestinal wounds.

A longitudinal intestinal wound model in the pig was used to assess the effect of parenteral steroids (betamethasone 12 mg 50 kg-1 intramuscularly twice daily) on breaking load. Steroid treatment significantly decreased the breaking load of wounds in the ileum and colon in comparison with wounds from saline-treated animals. In a further group of animals receiving steroids, paired longitudinal wounds were constructed. One wound of a pair was treated with a local application of transforming growth factor beta (TGF-beta) (5 micrograms per wound) or basic fibroblast growth factor (5 micrograms per wound) in a collagen suspension. The other wound was treated with a collagen suspension alone. Ileal wounds treated with TGF-beta were significantly stronger than collagen-treated controls at 7 days. The steroid-induced impairment of breaking load in intestinal wounds is partially reversed by a local application of TGF-beta in a collagen suspension at the time of surgery.

Animals↗

Recombinant basic fibroblast growth factor in red blood cell ghosts accelerates incisional wound healing.

The pharmacological manipulation of wound healing with locally applied growth factors is now a practical possibility. The effect of topical applications of recombinant basic fibroblast growth factor (bFGF) on the strength and cellularity of healing incisional rat skin wounds was investigated. Applications of bFGF in a simple vector (either a collagen suspension or saline) were not associated with any positive effects on wound breaking load at 7 days after injury in comparison with vector-treated control wounds; at the highest dose of 50 micrograms per wound, breaking loads were significantly decreased from a mean(s.e.m.) of 287(22) g/cm2 in controls to 201(23) g/cm2 (P < 0.005). Increasing doses of applied peptide were paralleled by increasing wound cellularity. Delay of bFGF release at the site of application was achieved by encapsulation into red blood cell ghosts. Wounds treated with bFGF in such ghosts were 50 per cent stronger than paired control wounds (388(27) versus 256(28) g/cm2, P < 0.002) 7 days after injury. Treated wounds were significantly more cellular at 4 days than paired control wounds. Topical applications of bFGF applied at the time of injury exert a positive effect on incisional wound strength only when a vector that delays release is used.

Administration, Topical↗

Peptide growth factors and wound healing.

Growth factors and cytokines are important signal transducers in wound microenvironments. Experimental data are accumulating rapidly which demonstrate their ability to influence populations of polymorphs and macrophages to migrate to the wound, subsequently to be replaced by synthetic cells which produce collagen and matrix; these events are controlled sequentially at cell receptor level by a variety of locally delivered (paracrine and autocrine) peptides. Preliminary results from clinical trials using recombinant human growth factors to improve cutaneous healing are encouraging. Current research aims to produce growth preparations which can be applied to a wound to accelerate healing.

Animals↗

Nutritional benefits of soy protein and soy fiber.

Soy protein and soy fiber are common ingredients in many foodstuffs. Various kinds of soy protein, including soy flour, soy-protein concentrate, and isolated soy protein, are currently used in human foods. Soy proteins are used in infant formulas and enteral nutrition products, as ingredients in meat products, and as protein supplements. Although it is a plant protein, the protein quality of soy protein is excellent. Soy fiber is used in enteral nutrition products and some bakery goods. Research shows that soy fiber provides the important health benefits usually associated with dietary fiber, including improved laxation and cholesterol-lowering ability. This review provides background information on soy protein and soy fiber and their use in human foods.

Diabetes Mellitus↗

Management of congenital adrenal hyperplasia using serum dehydroepiandrosterone sulfate and 17-hydroxyprogesterone concentrations.

Simultaneous serum concentrations of dehydroepiandrosterone sulfate (DHEA-S) and 17-hydroxyprogesterone (17-OHP) were compared with urinary 17-ketosteroid (17-KS) and pregnanetriol (PT) excretion during therapy in 18 prepubertal patients with the 21-hydroxylase deficiency form of congenital adrenal hyperplasia (CAH). Patients were classified into those in good, poor, or questionable control on the basis of clinical examination, skeletal age, and 17-KS and PT excretion. During therapy, use of serum steroid concentrations was found to be nearly as accurate in judging adequacy of control as use of urine steroid concentrations. Of 34 evaluations, a definite assessment of adequacy of control could be arrived at 25 times using urinary values and 22 times using both serum DHEA-S and 17-OHP concentrations. DHEA-S concentration responded sluggishly when treatment was not adequate, being greater than 100 microgram/dl only in patients significantly undertreated. It was never elevated in well-controlled patients. Mid-afternoon 17-OHP concentrations were less than 200 ng/dl in well-controlled patients but readily escaped suppression and could not be used to differentiate poor from borderline control or from temporary noncompliance. Therefore, an increases DHEA-S concentration indicated poor control and a suppressed 17-OHP concentration indicated good control. The combination of normal DHEA-S level with elevated 17-OHP level, however, did not permit exact evaluation of the degree of control. Of significance is that not all patients with CAH present with an elevated DHEA-S concentration, and only in those in whom an elevated level has been documented can DHEA-S level be used as an index of control during therapy.

17-Ketosteroids↗

Pylorus-preserving Kausch-Whipple resection: the successor of the classical Kausch-Whipple in chronic pancreatitis.

Chronic pancreatitis can be a debilitating disease. Resection for complicated disease and in those patients with intractable pain is a major component of therapy. There are potentially important physiological advantages with the pylorus preserving Kausch-Whipple (P-KW) compared to the standard Kausch-Whipple (KW) resection but further prospective studies are required to show this unequivocally. The Beger's operation also represents a significant theoretical advance. Indeed it permits resection in a proportion in whom a PP-KW or KW would not be possible technically because of severe fibrosis around the intra-pancreatic portal venous system. Although we have adopted the Beger's operation on our unit, large comparative studies are required against the KW and PP-KW procedures to properly establish its value. The hidden malignancy is an important issue, which undermines the routine use of the Beger's operation.

Chronic Disease↗